essay on smallpox history

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The Rise and Fall of Smallpox

By: Jesse Greenspan

Updated: August 24, 2023 | Original: May 7, 2015

Smallpox is believed to have first infected humans around the time of the earliest agricultural settlements some 12,000 years ago. No surviving evidence of it, however, predates the so-called New Kingdom of Egypt , which lasted from about 1570 B.C. to 1085 B.C. 

A few mummies from that era contain familiar-looking skin lesions. Ramses V, for example, who ruled for roughly four years in the 12th century B.C., looks to have had the raised bumps on his face and body for which smallpox is named (it’s derived from the Latin word for “spotted”). 

Moreover, an ancient Egyptian papyrus scroll briefly describes what could be smallpox, as do Hittite clay tablets. The Hittites, who lived in the Middle East, even accused the Egyptians of infecting them during a war between the two empires.

Many historians speculate that smallpox likewise brought about the devastating Plague of Athens in 430 B.C. and the Antonine Plague of A.D. 165 to 180, the later of which killed an estimated 3.5 million to 7 million people, including Emperor Marcus Aurelius , and hastened the decline of the Roman Empire . 

At any rate, it reached Europe no later than the 6th century, when a bishop in France unmistakably described its symptoms—a violent fever followed by the appearance of pustules, which, if the patient survived, eventually scabbed over and broke off. By that time, the contagious disease, caused by the variola virus, had spread all across Africa and Asia as well, prompting some cultures to worship special smallpox deities.

In the Old World, the most common form of smallpox killed perhaps 30 percent of its victims while blinding and disfiguring many others. But the effects were even worse in the Americas, which had no exposure to the virus prior to the arrival of Spanish and Portuguese conquistadors. 

Tearing through the Incas before Francisco Pizarro even got there, it made the empire unstable and ripe for conquest. It also devastated the Aztecs, killing, among others, the second-to-last of their rulers. In fact, historians believe that smallpox and other European diseases reduced the indigenous population of North and South America by up to 90 percent, a blow far greater than any defeat in battle. 

Recognizing its potency as a biological weapon, Lord Jeffrey Amherst, the commander-in-chief of British forces in North America during the French and Indian War , even advocated handing out smallpox-infected blankets to his Native American foes in 1763.

Knowing that no one can contract smallpox twice, survivors of the disease were often called upon to try and nurse victims back to health. Throughout much of the last millennium, this involved herbal remedies, bloodletting and exposing them to red objects. 

One prominent 17th-century English doctor realized that those who could afford care actually seemed to be dying at a higher rate than those who couldn’t. Yet that didn’t stop him from telling a smallpox-infected pupil to leave the windows open, to draw the bed sheets no higher than his waist and to drink profuse quantities of beer.

Far more effective was inoculation, also called variolation, which involved taking pus or powdered scabs from patients with a mild case of the disease and inserting them into the skin or nose of susceptible, healthy people. Ideally, the healthy people would suffer only a slight infection this way and, in so doing, would develop immunity to future outbreaks. 

Some people did die, but at a much lower rate than those who contracted smallpox naturally. Practiced first in Asia and Africa, variolation spread to the Ottoman Empire around 1670 and then to the rest of Europe within a few decades. Its first proponent in the present-day United States was Cotton Mather, a Puritan minister best known for vigorously supporting the Salem witch trials . Benjamin Franklin , who lost a son to smallpox, was another early American supporter.

Variolation notwithstanding, smallpox continued wreaking havoc on princes and paupers alike. In the 17th and 18th centuries, it killed several reigning European monarchs, including Habsburg Emperor Joseph I, Queen Mary II of England, Czar Peter II of Russia and King Louis XV of France, as well as an Ethiopian king, a Chinese emperor and two Japanese emperors. 

Queen Elizabeth I of England and U.S. President Abraham Lincoln also apparently contracted smallpox during their time in office, though they fortuitously lived to tell the tale. Meanwhile, in Europe alone, an estimated 400,000 commoners were succumbing to smallpox annually.

Finally, in 1796, English doctor Edward Jenner performed an experiment that would, in good time, cause the virus’ downfall. By inserting pus from a milkmaid with cowpox, a disease closely related to smallpox, into the arms of a healthy 8-year-old boy and then variolating him to no effect, Jenner was able to conclude that a person could be protected from smallpox without having to be directly exposed to it. This was the world’s first successful vaccine, a term that Jenner himself coined. He tried to get his results published by the prestigious Royal Society, only to be told not to “promulgate such a wild idea if he valued his reputation.” 

Persisting anyway, his vaccine gradually started catching on. The advantages over variolation were many. Unlike a variolated person, a vaccinated person could not spread smallpox to others. Moreover, the vaccine seldom left a rash and proved fatal in only the rarest of circumstances. 

“Future generations will know by history only that the loathsome smallpox existed and by you has been extirpated,” U.S. President Thomas Jefferson wrote to Jenner in 1806. The following year, Bavaria declared vaccination mandatory, and Denmark did the same in 1810.

Because the vaccine originally had to be transferred from arm to arm, its use spread slowly. It was also much less effective in tropical countries, where the heat caused it to quickly deteriorate. Nonetheless, one country after another managed to rid itself of the disease. The last reported U.S. case came in 1949.

Spurred by two new technological advances—a heat-stable, freeze-dried vaccine and the bifurcated needle—the World Health Organization then launched a global immunization campaign in 1967 with the goal of wiping out smallpox once and for all. That year, there were 10 million to 15 million cases of smallpox and 2 million deaths, according to WHO estimates. Yet just a decade later, the number was down to zero. No one has naturally contracted the virus since a Somali hospital worker in 1977 (though a laboratory accident in England did kill someone in 1978).

After searching far and wide for any remaining trace of smallpox, the WHO’s member states passed a resolution on May 8, 1980, declaring it eradicated. “The world and all its peoples have won freedom from smallpox,” the resolution stated, adding that this “unprecedented achievement in the history of public health … demonstrated how nations working together in a common cause may further human progress.” 

Today, guarded laboratories in Atlanta and Moscow hold the only known stores of the virus. Some experts say these should be destroyed, whereas others believe they should be kept around for research purposes just in case smallpox somehow remerges.

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The disease, now eradicated, was once one of the world's deadliest.

Smallpox ranks among the most devastating illnesses ever suffered by humankind. It dramatically altered the course of human history, even contributing to the decline of civilizations. Officially the deadly virus no longer exists. After a final outbreak in the United States in 1949, the virus was declared eradicated in 1980 following a successful vaccination program regarded as one of the greatest triumphs of modern medicine.

Smallpox is an acute contagious disease caused by the variola virus. It gets its name from the Latin word for "spotted," referring to the raised, pustular bumps that break out over the face and body of those affected. Historically the virus killed around 30 percent of people who caught it. Those who survived were often left blind, sterile, and with deep pitted scars, or pockmarks, on the skin.

Spread through direct contact with infected people, body fluids, or contaminated objects such as bedding, the disease had two main types. Variola major was the most common form–and most lethal. Variola minor produced a milder disease, which was fatal in less than one percent of cases. Two other, rarer forms also existed: hemorrhagic and malignant. Both invariably resulted in death.

Early Victims

Smallpox is thought to have originated in India or Egypt at least 3,000 years ago. The earliest evidence for the disease comes from the Egyptian Pharaoh Ramses V, who died in 1157 B.C. His mummified remains show telltale pockmarks on his skin.

The disease later spread along trade routes in Asia, Africa, and Europe, eventually reaching the Americas in the 1500s. Indigenous peoples there had no natural immunity. An estimated 90 percent of indigenous casualties during European colonization were caused by disease rather than military conquest.

Smallpox contributed to the decline of the Aztec Empire , in what is now Mexico, following the virus's arrival with Spanish conquerors in 1519. More than three million Aztec succumbed to the disease. Severely weakened, the Aztec were easily defeated. Likewise, smallpox claimed the life of an Inca emperor and wiped out much of the Inca population in western South America.

In Europe, smallpox is estimated to have claimed 60 million lives in the 18th century alone. In the 20th century, it killed some 300 million people globally.

Vaccination Victory

The human fight against smallpox dates back some 2,000 years. In Asia, a technique known as variolation involved deliberately infecting a person by blowing dried smallpox scabs up their nose. Those who received this treatment contracted a mild form of the disease, developing a lifelong immunity.

A key breakthrough came in 1796 when an experiment by English doctor Edward Jenner showed that inoculation using closely related cowpox could protect against smallpox. Jenner's discovery paved the way for later vaccination programs—especially crucial since there is no effective treatment for smallpox.

In 1967, a year when some 10 million to 15 million people contracted smallpox, the World Health Organization launched a worldwide eradication campaign based on vaccination. Gradually, the disease was pushed back to the Horn of Africa, and the last known natural case occurred in Somalia in 1977.

Despite being consigned to the history books, there's still a chance of smallpox coming back to haunt us—as a biological weapon. Such fears escalated dramatically in the United States following the September 11, 2001, terrorist attacks. While the risk of such a bioterror attack is considered very low, the U.S. has since stockpiled enough of the vaccine to inoculate every citizen.

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Smallpox and the story of vaccination

Published: 25 April 2019

Smallpox and vaccination are intimately connected. Edward Jenner developed the first vaccine to prevent smallpox infections, and this success led to the global eradication of smallpox and the development of many more life-saving vaccines.

Key facts about vaccination

Smallpox vaccination is based on a thousand-year old technique called inoculation, in which a small sample of infected matter is deliberately introduced into the body in order to prevent the full disease from developing. 

A vaccine stops you from getting an infectious disease by stimulating your body's immune system to produce chemicals called antibodies that will combat a future infection.

The first vaccine was developed to protect against smallpox, a deadly disease that killed thousands of people until the 1800s. Thanks to vaccination, smallpox was completely eradicated in 1979.

An antitoxin is a blood-based product that 'borrows' immunity from another person or animal to help you fight an infection, once you already have it.

The sciences of microbiology and immunology have produced different vaccines and antitoxins to prevent and combat a range of infectious diseases.

For a long time people observed that you rarely get the same infectious disease twice, or if you do it’s usually much milder the second time round.

What if you could artificially expose a person to a safer form of the disease before they encountered a potentially lethal version of the full disease? That might prevent them getting the full-blown disease if they encountered it in the future. This is the basis of vaccination, which itself is based on the thousand-year-old practice of inoculation.

Vaccination has saved millions, mostly children, from many potentially fatal diseases.

What is vaccination?

Vaccination is a medical technique that uses the body’s own immune system to protect it from infectious diseases.

A vaccine introduces a weakened or inactive version of the infection into the body. The person’s immune system reacts to the vaccine by producing antibodies (molecules in the blood that attack and destroy the infection).

Once someone has been vaccinated they are immune, which means that if they encounter the actual disease their body can fight off the infection before the disease takes hold.

Inoculation, or how to use the disease against itself

The first attempts to produce immunity artificially were recorded in China approximately a thousand years ago.

Healthy people would inhale a powder made from the crusts of smallpox scabs in order to protect themselves from the disease. They might show mild symptoms, but they were usually resistant to any subsequent exposure. The practice was called inoculation.

Another version of inoculation involved inserting powdered scab or pus from a smallpox pustule into a scratch on the skin made by a sharp instrument.

Inoculation was practiced in Asia and parts of Africa. It reached Europe and America via traveller's tales and experiences in the 1700s, where it was also called variolation, after the Latin name for smallpox—variola.

Cotton Mather, an American churchman, was told about inoculation by his enslaved worker, Onesimus  who had been inoculated as a child in Africa. In 1721, Mather campaigned for inoculation during an outbreak of smallpox in Boston and met with some success—but also much hostility.

Lady Wortley Montagu, wife of the British ambassador to Turkey, observed the scratch method of inoculation in Constantinople at seasonal inoculation ‘parties’. On returning to Britain, she had her children inoculated during a smallpox outbreak in 1721. She introduced the practice to London Society and even King George II had his children inoculated.  

Inoculation was an uncertain procedure and people sometimes developed the full-blown disease or inadvertently spread it to others while they were still infectious.

Edward Jenner and the smallpox vaccine

Smallpox was a highly infectious disease that was endemic around the world. The disease began with a fever and a red rash that spread all over the body. After a few days the rash turned into opaque pustules that formed scabs. The scabs fell off, often leaving deeply pock-marked skin.

In about 5–10% of cases (72% among children) a malignant form of smallpox was fatal. This is why people were so willing to inoculate their children. 

The English physician Edward Jenner (1749–1823) inoculated patients at his Gloucestershire practice.

In the surrounding countryside, he noticed a similar practice among local farming communities.

Milkmaids, who were renowned for their clear complexions, were often immune to smallpox and its scarring pock marks.

Their work brought them into contact with cowpox, a mild disease of cattle that only left a single pustule on the hands of people who milked the cows.  

Locals who were aware of this phenomenon began to inoculate themselves with the cowpox pustule as a way to ward off the more deadly smallpox. 

Jenner decided to test the effectiveness of this practice. In 1796 he took some matter from a cowpox pustule on the hand of milkmaid Sarah Nelmes and injected it into the arm of a young boy called James Phipps.

James developed a scab and experienced some soreness and mild fever for a day. Six weeks later, Jenner inoculated young James with smallpox matter and the boy showed no signs of the disease.

Jenner published his findings in a short treatise. He called the procedure vaccination after the Latin word for cow (vacca). Despite some opposition, vaccination soon replaced the riskier variolation and in 1853, 30 years after Jenner’s death, smallpox vaccination was a standard practice for preventing smallpox.

Today people can get vaccines against a whole host of infectious diseases, but smallpox is not one of them. Thanks to a global eradication programme of mass vaccination, the entire world population was officially free of this life-threatening disease by 1979.

Six lancets, steel and tortoiseshell in a shagreen and silver case, as used by Edward Jenner.

The science behind vaccination

Clinical practice proved Jenner’s vaccine successful, but neither he nor anyone else knew why it worked. An explanation had to wait for the science of bacteriology to develop at the end of the 1800s.

The French scientist  Louis Pasteur (1822–1895) believed that germs (microorganisms) were responsible for infectious diseases such as smallpox. He tested his 'germ theory of disease' on anthrax, an infectious disease of people and animals.

Through his microscope, he identified a microorganism in infected blood, which he believed was responsible for the disease. Pasteur developed a solution containing a weakened form of the bacteria, which he could use as an inoculating agent. He was able to measure the success of his experiment by the absence of bacteria in the inoculated host.

Pasteur called the process vaccination in honour of Jenner’s work on smallpox, and vaccination became the generic term for the technique.

The difference between antitoxins and vaccines

Both vaccines and antitoxins are derived from toxoids, modified bacterial toxins that stimulate protective antibodies in the blood. Antitoxins are used as a treatment or cure when the infection is already present in the person. Vaccines, on the other hand, are examples of prophylactics - they prevent a disease from developing by stimulating the body's immune system to produce antibodies in the blood.

If a person has a disease, their immune system is already overwhelmed by the infection so a vaccine wouldn't help. Antitoxins work by harnessing the immunity of another person or animal to boost the immune system of the infected person.

Antitoxins were developed by two researchers, Shibasaburo Kitasato (1852-1931) and Emil von Behring (1854-1917), who inoculated guinea pigs against diphtheria so they were immune to the disease. They then isolated a serum from the blood of the immunised animals and used it to treat guinea pigs that already had diphtheria. They found that the serum cured the sick animals of the disease. 

Antitoxins are made by collecting and purifying serum from animals (usually horses) inoculated with a non-lethal dose of disease toxin. Like vaccines, there are specific antitoxins for specific diseases, and the same technique is used for manufacturing treatments for other toxins such as snake venom.

Because antitoxins are not manufactured in the patient’s own blood, their effect only lasts a few weeks. This is enough to treat the disease if you already have it, but it doesn’t prevent you from getting it again. 

Vaccines don’t treat a disease, but prevent it from happening by stimulating the host to produce their own immunity, which can last for years.

Opposition to vaccination

In the 1800s, some people objected to compulsory vaccination because they felt it violated their personal liberty. The Vaccination Act of 1853 introduced mandatory smallpox vaccination in England and Wales for infants up to three months old. The Act was met with opposition from people who demanded the right to control their bodies and those of their children.

The Anti Vaccination League and the Anti-Compulsory Vaccination League formed in response to the mandatory laws, and numerous anti-vaccination journals sprang up. After a visit to New York, in 1879, by prominent British anti-vaccinationist William Tebb, The Anti-Vaccination Society of America was founded.

Despite the opposition to vaccination by some, smallpox was completely eradicated from the world 100 years after the Anti-Vaccination League was set up.

The significance of herd immunity

When a high percentage of the population is protected through vaccination, it becomes difficult for a disease to spread because there are so few susceptible people left to infect. This is called herd immunity. Herd immunity is crucial for protecting people who cannot be vaccinated, such as babies and people with compromised or ineffective immune systems.

In several countries, reductions in the use of some vaccines have been followed by increases in the number of cases of potentially lethal diseases, as herd immunity begins to break down. People can lose confidence in a vaccine for a number of reasons.

In the mid-1970s, a report from the Great Ormond Street Hospital for Sick Children in London alleged that 36 children suffered neurological conditions after having the DTP (Diphtheria, Tetanus and Pertusis) vaccine. Television documentaries and newspaper reports drew public attention to the controversy.

As a result, uptake of the DTP vaccine in the UK fell from 81% to 31%, and whooping cough (pertusis) epidemics followed, leading to the deaths of several children.

Public confidence was only restored after a national study identified every child between 2 and 36 months hospitalized in the UK for neurological illness, and determined that the risk was very low. DTP vaccine uptake eventually increased to levels above 90%, and disease incidence declined dramatically.

The MMR vaccine used to protect against measles, mumps and rubella.

Vaccination gives public health authorities something of a conundrum. When they succeed in vaccinating almost all of their communities, herd immunity kicks in and the incidence of a disease decreases. But if the next generation then has no memory of the trauma and danger of that disease, then public attention can shift from the significant risks in having the disease to the much lower risks from being vaccinated.

Suggestions for further research

• Edward Jenner, An inquiry into the causes and effect of the Variole Vaccinae , 1798
• Herve Bazin, The Eradication of Smallpox , 2000
• Gareth Williams, Paralysed with Fear: The Story of Polio , 2013
• Robert Gaynes, Germ Theory: Medical Pioneers in Infectious Diseases , 2011

Find out more about epidemics

Read more stories about how epidemics have affected people and places around the world.

Polio: a 20th century epidemic

While many infectious diseases began to decline by the end of the 19th century, incidents of polio increased to epidemic proportions. What was going on?

Jenner's medicine chest

Take a look at Edward Jenner's medicine chest in this learning resource for teachers.

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History of smallpox: Outbreaks and vaccine timeline

Learn about the development, use and impact of the smallpox vaccine.

Dr. Edward Jenner

Dr. Edward Jenner vaccinates his child against smallpox.

Dr. Edward Jenner finds that vaccination with the cowpox virus can protect a person from smallpox infection and creates a smallpox vaccine. He publishes his findings in 1798.

Dr. Benjamin Waterhouse

Dr. Benjamin Waterhouse gives the first smallpox vaccinations in the U.S.

Dr. Benjamin Waterhouse gives the smallpox vaccine to his son and other family members. These smallpox vaccinations are the first in the U.S.

Massachusetts is the first state to require that children have a smallpox vaccine before going to school to prevent the spread of smallpox in schools.

The World Health Organization (WHO) declares smallpox eliminated worldwide due to vaccinations. Smallpox vaccination ends. Before the smallpox vaccine, smallpox had been considered one of the deadliest infectious diseases. About 300 million people died of smallpox in the 20th century.

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Article Contents

Early vaccines, vaccination after 1900, eradication strategy evolution, eradication and vaccine quality, vaccine potency, stability, and bacterial content in 1967, administration of vaccine, vaccine complications, smallpox: the disease, the eradication program, surveillance containment and ring vaccination, certification, continuing issues, supplementary data.

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Joel G Breman, Smallpox, The Journal of Infectious Diseases , Volume 224, Issue Supplement_4, 1 October 2021, Pages S379–S386, https://doi.org/10.1093/infdis/jiaa588

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You have erased from the calendar of human afflictions one of its greatest. Yours is the comfortable reflection that mankind can never forget that you have lived. Future nations will know by history only that the loathsome smallpox has existed and by you has been extirpated. Thomas Jefferson, writing to Edward Jenner in 1806 [1].

Before knowledge and use of vaccines, protection against smallpox was practiced more than a thousand years ago by traditional approaches. Invoking the good graces of smallpox gods, goddesses, and saints by individuals and communities was common [ 2 ]. Isolation of patients was the only means known to appease and contain the bad spirits that brought and spread the disease.

Traditional medical practitioners in some areas of China, India, Egypt, Ethiopia, and elsewhere collected materials from the pustules or crusts of the afflicted and inserted these into the noses or skin of healthy persons seeking protection [ 2 ]. This procedure, called inoculation or variolation, probably had little effect on curtailing epidemics because of its limited use and variability of potency of the inoculum.

It is remarkable that some early inoculators inserted scabs into the nose, without understanding that smallpox is acquired via the respiratory route, and, that scratching pustular material into the skin could have the same salutary effect. Nasal inoculation or dermal variolation, using material containing live virus, resulted sometimes in mild illness and protection. However, some cases of smallpox in recipients had the potential to spread within persons and communities.

Edward Jenner, the country doctor from Berkeley, Gloucester, England, is recognized as the father of smallpox vaccination. Jenner’s 1796 observations, that cowpox protected against smallpox when scratched into the skin of recipients, were written up in detail and presented to the Royal Society of England in 1798 and promoted widely in letters [3]. Yet Jenner was not the first to make these observations.

Some historians note that John Fewster and others, as early as 1768, living near Jenner in Thornbury, and Benjamin Jesty in 1774 in Westminster, United Kingdom, observed the benefits of cowpox inoculation for protecting humans against smallpox [4]; these observations were not documented and disseminated, however, so they remain in obscurity.

Jenner promoted vaccines in England and elsewhere by letters and speeches and by giving vaccinations gratis to local residents at the “vaccine hut” outside his home (The Chantry). There was immediate fierce opposition by persons who believed that biological products from cows would result in growths resembling cows on the bodies of recipients.

People of influence had an early role in supporting both inoculation and vaccination. Lady Mary Wortley Montagu, wife of the UK Ambassador to Turkey, who had had smallpox in England, observed variolators in Turkey performing inoculations. She was so impressed that she promoted the procedure via a series of letters starting in 1717 [1, 2 ]. Thomas Jefferson, Benjamin Franklin, and Benjamin Waterhouse, the latter of Harvard University, were early advocates of vaccination in the United States.

For the next 100 years, technical problems tied to vaccine quality impeded the successful use of vaccine globally. Well into the 20th century, the major challenges were growing adequate quantities of vaccine of measurable potency, sterility, and durability despite differences in temperature, climate, and humidity [5].

Mode of administration was another challenge. Different scratch and inoculation techniques were used, particularly in India [ 6 ]. Throughout much of the 1800s vaccine was passed from arm to arm or dried and put on small “points” (sharp objects of ivory, steel). These methods were not reliable. Toward the end of the 19th century, animals, especially the skin of living cows, were used to grow the virus used for vaccination [5].

During the 19th century, arm-to-arm vaccination was the standard method of maintaining the product’s efficacy, even during long voyages. Some practitioners put threads through the pustular material. The threads were dried and sent to the areas for populations to be vaccinated; potency certainly waned during such travel. On long sea voyages, groups of orphan children were often sent specifically to assure arm-to-arm transfer of the pustular material. In the early 1900s, an attempt to dry and preserve vaccine for shipment from France to their colonies in West Africa was described by Fasquelle and Fasquelle [7].

Pustular material from cows or patients with pustular disease of indeterminate origin was used for more than a century as the source of smallpox vaccine. By the beginning of the 1900s, vaccination against smallpox was being practiced in most industrialized countries. The virus now used, called vaccinia, has an obscure origin. The product may have originally been a hybrid between cowpox virus and variola virus or some other orthopoxvirus by serial passage in artificial conditions, or, as Baxby posits, vaccinia may be a laboratory survivor of a virus now extinct [ 8 ], p 214]. The various vaccinia strains globally are similar to each other genetically but differentiated from other poxviruses, including cowpox and variola viruses, by DNA mapping. By the 1950s there was improvement in vaccine quality, distribution, and public health infrastructure. Smallpox was virtually eliminated from Europe and North America by that time.

Since Jenner’s time opponents of vaccination have based their concerns on perceived physical harm from the procedure and breaching of individual rights. Over time, vaccination has been considered a public health good and inserted into law in the United States and elsewhere and upheld by the Supreme Court [9].

High vaccination coverage had been the strategy of national and international smallpox control and elimination strategies since Jenner’s findings slowly spread worldwide and became accepted in the 1800s. However, the continued existence of the disease on virtually all continents was due to fragmented and inadequate health systems. Access to remote populations was impossible in many areas and acceptance of evolving vaccine production and delivery technology was slow. Most importantly, the colonial legacy starting in the late 1800s left many areas of the world dependent on European control and resources for their health and other programs, particularly in Africa. Conservation of liquid vaccine produced mainly on cows was very difficult, because refrigeration was virtually nonexistent in the tropics until the mid- to late-1900s.

In West and Central Africa and India more vaccinations were given than the censused population, yet smallpox raged because of poor vaccine quality. Massive epidemics of smallpox appeared periodically in virtually all tropical countries and several areas of temperate countries well into the 1900s, fueled by high levels of susceptibility as a result of new births, those who received poor quality vaccine, and nonimmune older persons [10].

The World Health Organization (WHO) was formed in 1948 with a mandate to develop public health policies and to coordinate surveillance, and some control and eradication initiatives. By the 1950s, many countries had passed public health laws and implemented smallpox vaccination programs, many of which were successful, particularly in the northern hemisphere. In 1959, the representative of the Soviet Union proposed a resolution for a global smallpox eradication program to the World Health Assembly [ 2 ]; this was based, in part, on the outbreaks of smallpox in several of the southern republics, which underscored the priority for development of a potent vaccine to control the outbreaks. In addition, the Soviets wished to provide vaccines to the WHO as a gift to the global program. Yet, little progress was made over the next 6 years toward global eradication [ 11 ], p 334].

Between 1959 and 1966, few funds were received or invested by WHO for smallpox eradication, and few staff were assigned to the program. The strategy was entirely reliant on attempting to achieve 80% vaccination coverage. Each country had to rely on its own manufacturers or products acquired via the WHO, mainly from Soviet donations. The Soviet product caused severe adverse reactions, which probably was responsible for poor acceptance and coverage, especially in India, where tens of millions of doses were sent [ 2 ].

Despite the 1959 resolution, WHO internal and external support for the program languished until the middle 1960s. In 1966, the United States, backed by President Lyndon Johnson, supported another resolution in support of an intensified smallpox eradication program [ 11 ], p 334].

By the late 1960s, when the intensified global smallpox eradication program began, it was found by WHO, that vaccine was being produced by many different countries using varying procedures. A major step was taken initially by the Smallpox Eradication Unit at WHO to advise standardized production methods and international quality control of vaccines used in the global program [ 2 ].

One of the first steps of the intensified program was to do a detailed survey of vaccine production procedures, quality, and production capacity in endemic and nonendemic countries. Questions about the relatively newly perfected freeze-dried vaccine methods, strains used, methods of growing virus, and bottling (doses per vial) were assessed [ 2 , 12 ].

Of 72 laboratories assessed, 59 replied to the WHO survey. Fifty-one laboratories (86.4%) harvested vaccinia virus from the skin of calves or sheep, and 6 (10.1%) from water buffaloes; 3 also reported using chick embryos, and 3 used tissue culture. Of the 59 laboratories, 23 (39.0%) used Lister strain (origin UK), 6 (10.2%) New York City Board of Health strain, 7 (11.9%) Paris strain, and 22 (37.3%) a variety of strains; one reported using a mixture of vaccinia and cowpox.

When the WHO requested laboratories producing smallpox vaccines to submit information on potency, heat stability and bacterial content, the following was received from 59 laboratories from 4 WHO regions. Of the 59, 31 (52.5%) reported that all 3 recent product lots were satisfactory (titers of ≥10 8.0 pock-forming units on chicken chorioallantoic membranes), and 16 (27.1%) reported vaccine stability after 4 weeks at 37°C; 12 of 53 laboratories (22.6%) sending data reported bacterial counts >500/mL, which were unacceptable by WHO standards.

After the establishment of the independent WHO reference centers for smallpox vaccine testing at Connaught Laboratories in Toronto and the National Institute of Public Health in Bilthoven, the Netherlands, it was concluded that, of 39 batches submitted by producers intending to develop freeze-dried vaccine for use in their own countries and in the global programs, 25 (64.1%) failed to meet standards. The conclusion was that, in 1967, not more than 10% of the vaccine in use in endemic countries met WHO requirements. Freeze-dried vaccine, a procedure credited to Leslie Collier, rendered the vaccine stable for long periods and could be reconstituted with diluent in the field [ 12 ].

The WHO smallpox unit established (1) a manual on the production of freeze-dried vaccine, (2) a traveling set of experts who gave seminars on vaccine production in laboratories, (3) training that including hands-on demonstration of the production of reference smallpox vaccines, (4) provision of seed lots of Lister strain vaccinia, (5) development of a heat stability test, and (6) guidance for regular testing of vaccine potency and heat stability to be used by the reference centers.

Another reason earlier smallpox campaigns failed was the inadequacy of the instruments used to immunize. Baxby has reviewed the variety of instruments, many of which resembled “tools of torture” [ 13 ]. Some of these required large amounts of liquid vaccine and caused maceration of the skin. This often resulted in infections in the tissues of recipients, poor success rates, and refusal of the procedure.

The 2 most effective tools for injecting vaccinia virus intradermally during the eradication program were the bifurcated needle and the jet injector gun ( Figures 1 and 2 ). The bifurcated needle is a 2-pronged adaptation of a sewing needle, invented by Benjamin Rubin of Wyeth Laboratories. The sterile needle was dipped into a reconstituted vial of vaccine; a drop of vaccine was caught between the prongs. The needle is jabbed rapidly 15 times into the upper deltoid region of the arm until a small drop of blood or serum appears. The jabs should all be within a 1-cm-diameter area. Acetone is preferable to alcohol for cleansing the arm because it dries quickly; alcohol could inactivate the vaccinia virus if not dry when the multiple punctures are made. The needles are kept in a durable tubular container with a hole to shake out a sterile metal needle when needed. The needles are cleaned after use, placed in a tub of boiling water for 20 minutes, cooled, and replaced in the plastic containers, ready for reuse.

Bifurcated needle for intradermal injection of vaccinia virus, invented by Benjamin Rubin (left) of Wyeth Laboratories. (Source: Fenner et al [ 2 ], WHO.)

Jet injector for intradermal injection of vaccinia virus. Top left, Intradermal nozzle squirts at an angle for smallpox vaccination. Top right, Jet Injector in its case. The instruction book for West Africa was in English and French. Bottom right, Aaron Ismach, who is credited with the design of this injector. (Source: WHO, CDC)

The jet injector is a pneumatic foot-activated apparatus (gun) that injects smallpox vaccine intradermally via a special nozzle. It was most effective in places where large groups of people could be assembled, such as Brazil and West and Central Africa. Aaron Ismach of the US Army is credited with the design. The apparatus has been criticized for requiring frequent maintenance and spare parts; however, in Guinea, for example, 6 vaccination teams averaged close to 2000 vaccinations per working day over a 2-year period in a rural environment where people could be assembled; meticulous attention was given to daily maintenance [14]. Not only was coverage high with both of these devices during the smallpox eradication campaign, but the success (“take”) rates after vaccination were >98% in primary vaccines and 95% in those receiving revaccination (see Figure 3 ).

Skin reaction after primary vaccination and late revaccination (several years later), performed using a multiple puncture method or a jet injector. (Source: CDC.)

Smallpox vaccine multiplies in the skin’s epithelium, producing a slight fever and characteristic skin reaction with redness and induration leading to a pustule by about day 7 in those receiving primary vaccines; this “Jennerian pustule” usually starts to crust and desquamate by day 14, leaving a scar. Induration may occur after revaccination; if many years have passed since vaccination, a typical Jennerian vesicle will occur ( Figure 3 ).

During the intensified eradication program, a major effort was made to assess take rates. Only in the United States was a comprehensive nationwide survey done to look at adverse events following smallpox vaccination with the NY Board of Health seed strain. In 1970 and 1971, Lane et al published articles on complications, dividing United States recipients into those receiving smallpox vaccine for the first time (primary vaccinees) and those receiving the vaccine as “revaccinees” [ 15 , 16, 17]. Data from the 10-state survey were collected by more active ascertainment of adverse events, resulting in 5 times the number of complications reported by the passively reported events [ 15 ]. The most severe conditions were postvaccinal encephalitis and generalized vaccinia ( Figure 4 ). The death rate was about 1 in 1 million vaccinations in those receiving primary vaccines, mainly young children. Children with immunoglobulin deficiencies or severe eczema were prone to adverse events. Screening before vaccination could have decreased the number of complications.

Accidental autoinoculation of cheek with vaccinia virus, approximately 5 days old. Primary take with “Jennerian vesicle” on arm, 10–12 days old. (Photograph courtesy of John M. Leedom, MD, CDC collection.)

In 1971, the US Advisory Committee on Immunization Practices recommended that routine smallpox vaccination be stopped in the United States. This was based on the assessment of the risks of those being vaccinated and the extremely low chance of importation, even though smallpox remained endemic in East Africa and the Indian subcontinent [18, 19].

Following the certification of smallpox eradication by the World Health Assembly in 1980, the WHO advised all countries to stop routine smallpox vaccination [ 2 ]. This was accepted by virtually all countries in the early 1980s. In 2002–2003, after the terrorist airplane attacks on the Twin Towers buildings in New York City and the anthrax mailings and deaths due to a domestic bioterror event, a limited number of smallpox vaccinations were given in the United States, mainly to first responders. The US military was vaccinated, and acute myopericarditis and cardiac arrhythmias developed in 37 of >400 000 recruits [17, 18].

There were 2 major manifestations of smallpox: Variola major and Variola minor. V. major was seen mainly in the Indian subcontinent, and parts of Africa and Asia during the eradication program and was the most severe form, with a 30% fatality rate. V. minor, observed in east of Africa and Latin America, was milder, with fewer lesions and a case fatality rate of <5%. The clinical and epidemiological features of smallpox have been well covered in recent and past literature and are summarized in Tables 1 and 2 [ 2 , 20 ]. The eruption evolves with all skin lesions at the same stages at a given point of time, starting from macules and papules, followed by pustules, vesicles, and finally crusts, over a 10–20-day period.

Clinical and Epidemiological Features of Smallpox and Considerations for Certification

Characteristics of Surveys to Certify Eradication of Smallpox

The lesions of smallpox are focused on the peripheral (centrifugal) parts of the body ( Figure 5 ), in contrast to the rashes of diseases like chickenpox which have centripetal distribution. The most common diagnostic dilemma is in the differential diagnosis is chickenpox which can be severe in older persons and immunocompromised patients [ 20 ]. Today, in Africa the eruption of human monkeypox cannot be easily distinguished from smallpox except by laboratory testing; patients with monkeypox often have cervical and inguinal lymphadenopathy [21].

Smallpox on day 8 of eruption (World Health Organization photograph).

The initial strategy of the intensified smallpox eradication program beginning in 1967 was based on at least 80% vaccination coverage of the population in each country. This strategy, while successful in northern countries where vaccine quality was monitored and people were told to be revaccinated every 3 years, was not effective in the heavily endemic areas. These countries were mainly in Africa, Latin America, and Asia. In Africa, the health infrastructure was poor, because many countries became newly independent in the late 1950s and 1960s and had limited resources. Some countries had a tradition of mobile health teams trained to detect perils, such as sleeping sickness, leprosy, and onchocerciasis, and to give smallpox vaccines. The countries did not often have managerial expertise or refrigerated repositories to conserve vaccines and other heat-sensitive biologicals [22, 23].

In the mid-1960s President Lyndon Johnson committed the United States to supporting an 18-country West and Central Africa smallpox eradication-measles control program. This followed a visit to the United States by the minister of health of Burkina Faso (then Upper Volta), who learned about the newly developed measles vaccine and wanted Africa to benefit. The funding came via the US Agency for International Development. The US Centers for Disease Control and Prevention (CDC; then the Communicable Disease Center) was the implementing organization.

Of the 11 countries with the highest incidence of smallpox, 7 were in West and Central Africa. Two major innovations in this program have changed the face of public health. The first was the use of operational specialists from the CDC—managers responsible for organization, finances, equipment, supplies, logistics, transportation—who were assigned to countries with medical epidemiologists, both of whom worked closely with national counterparts [24], p 141].

Second, the concept of surveillance containment was rediscovered and refined in Nigeria [ 25 ]. Intensified surveillance and ring vaccination became the major strategies used throughout the program, especially in the Indian subcontinent [ 2 , 26, 27].

Using epidemiological information, rumor notices, and village-by-village searches, persons with suspected smallpox were identified and confirmed virologically when outbreaks were few. Patients were isolated in or near their home residence; food was supplied, and a 24-hour guard hired by the program to assure the patient did not circulate until the crusts had fallen. All primary contacts of the patient since the illness began were identified and vaccinated, as were residents of neighboring houses and villages within 5 km.

Detailed maps and censuses of houses and residents in the villages within 5 km of the patient were made and used to assure all occupants had been vaccinated. Cross-notification was done, by telegram or phone, to health authorities both from places where case patients had probably acquired their disease and from places they had visited since their infections first manifested. Secondary areas of priority (nearby villages, markets, schools, assembly areas) were identified on hand-drawn maps and were visited, and residents were interrogated and vaccinated. This strategy is also called “ring vaccination,” as concentric circles or areas of priority were often mapped by program authorities.

In the Indian subcontinent, the active case search approach was highly refined. At one time 150 000 field workers were going from village to village [26, 27]. Major increases in numbers of infected villages and cases were found, compared with routine reporting. The largest exportation of cases in the program occurred in India. The Tatanagar railway station was the source of dozens of cases in surrounding states and districts until the case tracking and containment strategy was intensified, with major assistance from Tata industries that joined the program with staff and funds [27]. In Bangladesh, it was found by facial pockmark surveys that <5% of the actual cases were being reported before the program began [ 28 ].

The last case caused by naturally occurring transmission of Variola major occurred in Bangladesh in October 1975, and the last of disease Variola minor in Somalia on 26 October 1977 ( Figures 6 and 7 ). In 1978, an outbreak of smallpox occurred in Birmingham, United Kingdom, associated with a laboratory working with poxvirus variola virus: the ducting system connecting the laboratory to a photographer’s office above was the conduit of contamination [ 2 ].

Last case patient with Variola major smallpox (Bangladesh, 1975). (Source: World Health Organization.)

Last case patient with naturally transmitted smallpox (October 1977). (Source: World Health Organization.)

After a series of independent evaluations, including field visits to formerly endemic counties by separate international commissions, the Global Commission for the Certification of Smallpox Eradication concluded that eradication had been achieved in December 1979 ( Tables 3 and 4 ). The number of laboratories with variola virus was reduced from 76 to 6 by May 1980, when the World Health Assembly accepted the recommendations of the Global Commission that eradication had indeed been achieved [ 29 ]; there are now only 2 laboratories known to retain variola virus stocks—Vektor in Novosibirsk, Russia, and at the CDC in Atlanta. Both laboratories are visited every 2 years by biosafety experts convened by WHO, to assure that maximum biocontainment of the variola isolates is assured.

Smallpox Certification Activities in 200 Countries, 1977–1980 a

a A total of 17 000 specimens were collected.

Smallpox Certification Activities in India: Facial Pockmark Surveys, 1977

a Pockmarks due to smallpox contracted before 1975.

There remains concern that a bioterrorist event using smallpox virus could occur; this would wreak havoc globally [30]. The CDC has a smallpox response plan that focuses on national leadership, community-based planning, public health response actions, and health care facility response activities. The US national vaccine stockpile maintains 3 vaccines [ 31 , 32, 33]. ACAM2000 is a Food and Drug Administration–licensed vaccine grown on tissue culture, derived from the New York Board of Health strain of vaccine used to make Dryvax; this latter product was used widely in the eradication program. Aventis Pasteur smallpox vaccine is a vaccine supply created in the 20th century but still retaining potency. The Imvamune vaccine (Bavarian Nordic) uses modified vaccinia Ankara, a nonreplicating vaccine that requires 2 injections and is thought to elicit fewer adverse events, especially in immunologically deficient persons; it is not yet licensed.

The Food and Drug Administration has recently approved Tecovirimat for the treatment of smallpox; this drug is also destined for the US national stockpile [34]. The WHO, likewise, has a smallpox preparedness plan. Their operational framework addresses education, laboratory diagnosis, biosafety and security, provision of expertise and supplies, and the strengthening of national level responses. WHO also maintains an emergency vaccine stockpile.

The de novo synthesis of horsepox virus has raised concern that a terrorist could recreate variola virus [ 35 ]. Because routine smallpox vaccination stopped in the United States in 1971 and globally in the early 1980s, there is justifiable concern over population vulnerability. Constant vigilance for dealing with a return of smallpox is warranted. The 2 high security repositories of variola virus stocks, at CDC in Atlanta, and at Vektor in Novosibirsk, Russia, are inspected periodically by WHO. Periodic debates at the World Health Assembly over whether to destroy the remaining known stocks of smallpox virus have not concluded it was time to do so.

Another important continuing issue is the increasing number of outbreaks and cases of human monkeypox in central and western Africa [36, 37 ]. These outbreaks will increase as population immunity falls. The smallpox vaccine protects against monkeypox. At some point, consideration must be given whether vaccinia should be used for vulnerable populations in monkeypox-endemic areas.

Supplementary materials are available at The Journal of Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

The complete references are available as online Supplemental Material.

Acknowledgments. Thanks to Leigh Henderson, PhD, for help with graphics and Mantra Singh for secretarial assistance.

Supplement sponsorship. This supplement is sponsored by the Bill and Melinda Gates Foundation.

Potential conflicts of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Fenner F , Henderson DA , Arita I , Ježek Z , Ladnyi ID. Smallpox and its eradication . Geneva, Switzerland : World Health Organization , 1988 .

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The Spread and Eradication of Smallpox

Smallpox began causing illness and death more than a thousand years ago. follow its spread and eventual eradication in the timeline below., smallpox is present in the egyptian empire.

Traces of smallpox pustules found on the head of a 3,000-year-old mummy of the Pharaoh Ramses V. By G. Elliot Smith, Public Domain.

A written description of a disease that clearly resembles smallpox appears in China

In China, people appealed to the god Yo Hoa Long for protection from smallpox. Image taken from Recherche sur les Superstitions en Chine (Research on Chinese Superstitions) by Henri Dore, Shanghai, 1911-1920. Bibliotheque nationale de France.

Increased trade with China and Korea introduces smallpox into Japan.

Drawing of a woman defeating the “smallpox demon” by wearing red. A myth commonly believed around the world advocated that red light would cure smallpox. In Japan, families who fell sick with smallpox set up shrines to the “smallpox demon” in their homes with the hope they would appease the demon and be cured. By Sensai Eitaku (鮮斎永濯, Japanese, *1843, †1890) – scanned from ISBN 978-4-309-76096-4., Public Domain]

Smallpox is widespread in India. Arab expansion spreads smallpox into northern Africa, Spain, and Portugal.

Figurine of Indian smallpox goddess Shitala Mata worshipped in northern India. She was considered both the cause and cure of smallpox disease. Symbolically, she represents the importance of good hygiene in people’s health and motivates worshipers to keep their surroundings clean. Photo courtesy of the National Library of Medicine.

Smallpox spreads to Asia Minor, the area of present-day Turkey.

The map shows the Ottoman Empire in 1801, which then extended from Turkey (Anatolia) to Greece, Hungary, Bulgaria, Romania, as well as northern Africa and parts of Middle East. Smallpox is thought to arrive to the area from Asia through major trade routes, like the Silk Road.

Entrance into Europe

Crusades further contribute to the spread of smallpox in Europe with the European Christians moving to and from the Middle East during the next two centuries.

Smallpox moves north

Population expansion and more frequent travel renders smallpox endemic in previously unaffected Central and North Europe, with severe epidemics occurring as far as Iceland.

Smallpox is widespread in many European countries, and Portuguese expeditions to African west coast and new trade routes with eastern parts of Africa introduce the disease into West Africa.

Statue of Shapona, the West African god of smallpox. Smallpox was thought to be a disease forced upon humans due to Shapona’s “divine displeasure,” and formal worship of the god of smallpox was highly controlled by specific priests in charge of shrines to the god. People believed that the priests themselves were capable of causing smallpox outbreaks. Even though the British colonial rulers banned the worship of Shapona in 1907, worship of the deity continued. Source: CDC, photo credit James Gathany.

European colonization and the African slave trade import smallpox into the Caribbean and Central and South America.

Illustration by the Franciscan missionary Bernardino de Sahagun who wrote detailed accounts of the Aztec history during his life there from 1545 until his death in 1590 into 12 books entitled “General History of the Things of New Spain.” Introduction of smallpox into Mexico by the Spanish around 1520 was one of the factors that led to the demise of Aztec Empire. Scanned from (2009) Viruses, Plagues, and History: Past, Present and Future, Oxford University Press, USA, p. 60. Public Domain.

Variolation—a process of grinding up dried smallpox scabs from a smallpox patient and inhaling them or scratching them into an arm of an uninfected person—is being used in China (inhalation technique) and India (cutaneous technique) to control smallpox.

A container from Ethiopia used to store the powdery variolation material, which was produced by grinding up dried smallpox scabs taken from a smallpox patient. Source: CDC, photo credit Brian Holloway.

Increased use of variolation

Variolation (cutaneous technique) is a widespread method for preventing smallpox in the Ottoman Empire (former Asia Minor, present-day Turkey) and North Africa.

Smallpox spreads into North America

European colonization imports smallpox into North America.

Variolation is introduced into England by Lady Mary Wortley Montagu, the wife of the British ambassador to Turkey.

Lady Mary Wortley Montagu, the wife of the British ambassador, learned about variolation during their appointment in Turkey. A survivor of smallpox herself, she had both of her children variolated and was the foremost person responsible for the introduction of the technique to England.

In 1796, Edward Jenner, an English doctor, shows the effectiveness of previous cowpox infection in protecting people from smallpox, forming the basis for vaccination.

Edward Jenner (1749–1823). Photo courtesy of the National Library of Medicine.

Smallpox is widespread in Africa, Asia, and South America in the early 1900s, while Europe and North America have smallpox largely under control through the use of mass vaccination.

The map shows the worldwide distribution of smallpox and the countries in which it was endemic in 1945. Source: CDC, photo credit Dr. Michael Schwartz.

After a global eradication campaign that lasted more than 20 years, the 33rd World Health Assembly declares the world free of smallpox in 1980.

WHO poster commemorating the eradication of smallpox in October 1979, which was later officially endorsed by the 33rd World Health Assembly on May 8, 1980. Courtesy of WHO.

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• v.18(1); 2005 Jan

Edward Jenner and the history of smallpox and vaccination

Stefan riedel.

1 From the Department of Pathology, Baylor University Medical Center, Dallas, Texas.

In science credit goes to the man who convinces the world, not the man to whom the idea first occurs. — Francis Galton

For many centuries, smallpox devastated mankind. In modern times we do not have to worry about it thanks to the remarkable work of Edward Jenner and later developments from his endeavors. With the rapid pace of vaccine development in recent decades, the historic origins of immunization are often forgotten. Unfortunately, since the attack on the World Trade Center on September 11, 2001, the threat of biological warfare and bioterrorism has reemerged. Smallpox has been identified as a possible agent of bioterrorism ( 1 ). It seems prudent to review the history of a disease known to few people in the 21st century.

Edward Jenner (Figure ​ (Figure1 1 ) is well known around the world for his innovative contribution to immunization and the ultimate eradication of smallpox ( 2 ). Jenner's work is widely regarded as the foundation of immunology—despite the fact that he was neither the first to suggest that infection with cowpox conferred specific immunity to smallpox nor the first to attempt cowpox inoculation for this purpose.

Edward Jenner (1749–1823). Photo courtesy of the National Library of Medicine.

SMALLPOX: THE ORIGIN OF A DISEASE

The origin of smallpox as a natural disease is lost in prehistory. It is believed to have appeared around 10,000 BC , at the time of the first agricultural settlements in northeastern Africa ( 3 , 4 ). It seems plausible that it spread from there to India by means of ancient Egyptian merchants. The earliest evidence of skin lesions resembling those of smallpox is found on faces of mummies from the time of the 18th and 20th Egyptian Dynasties (1570–1085 BC ). The mummified head of the Egyptian pharaoh Ramses V (died 1156 BC ) bears evidence of the disease ( 5 ). At the same time, smallpox has been reported in ancient Asian cultures: smallpox was described as early as 1122 BC in China and is mentioned in ancient Sanskrit texts of India.

Smallpox was introduced to Europe sometime between the fifth and seventh centuries and was frequently epidemic during the Middle Ages. The disease greatly affected the development of Western civilization. The first stages of the decline of the Roman Empire ( AD 108) coincided with a large-scale epidemic: the plague of Antonine, which accounted for the deaths of almost 7 million people ( 6 ). The Arab expansion, the Crusades, and the discovery of the West Indies all contributed to the spread of the disease.

Unknown in the New World, smallpox was introduced by the Spanish and Portuguese conquistadors. The disease decimated the local population and was instrumental in the fall of the empires of the Aztecs and the Incas. Similarly, on the eastern coast of North America, the disease was introduced by the early settlers and led to a decline in the native population. The devastating effects of smallpox also gave rise to one of the first examples of biological warfare ( 1 , 7 ). During the French-Indian War (1754–1767), Sir Jeffrey Amherst, the commander of the British forces in North America, suggested the deliberate use of smallpox to diminish the American Indian population hostile to the British. Another factor contributing to smallpox in the Americas was the slave trade because many slaves came from regions in Africa where smallpox was endemic.

Smallpox affected all levels of society. In the 18th century in Europe, 400,000 people died annually of smallpox, and one third of the survivors went blind ( 4 ). The symptoms of smallpox, or the “speckled monster” as it was known in 18th-century England, appeared suddenly and the sequelae were devastating. The case-fatality rate varied from 20% to 60% and left most survivors with disfiguring scars. The case-fatality rate in infants was even higher, approaching 80% in London and 98% in Berlin during the late 1800s.

The word variola was commonly used for smallpox and had been introduced by Bishop Marius of Avenches (near Lausanne, Switzerland) in AD 570. It is derived from the Latin word varius , meaning “stained,” or from varus , meaning “mark on the skin.” The term small pockes ( pocke meaning sac) was first used in England at the end of the 15th century to distinguish the disease from syphilis, which was then known as the great pockes ( 8 ).

VARIOLATION AND EARLY ATTEMPTS OF TREATMENT

It was common knowledge that survivors of smallpox became immune to the disease. As early as 430 BC , survivors of smallpox were called upon to nurse the afflicted ( 9 ). Man had long been trying to find a cure for the “speckled monster.” During medieval times, many herbal remedies, as well as cold treatment and special cloths, were used to either prevent or treat smallpox. Dr. Sydenham (1624–1689) treated his patients by allowing no fire in the room, leaving the windows permanently open, drawing the bedclothes no higher than the patient's waist, and administering “twelve bottles of small beer every twenty-four hours” ( 10 ).

However, the most successful way of combating smallpox before the discovery of vaccination was inoculation. The word is derived from the Latin inoculare , meaning “to graft.” Inoculation referred to the subcutaneous instillation of smallpox virus into nonimmune individuals. The inoculator usually used a lancet wet with fresh matter taken from a ripe pustule of some person who suffered from smallpox. The material was then subcutaneously introduced on the arms or legs of the nonimmune person. The terms inoculation and variolation were often used interchangeably. The practice of inoculation seems to have arisen independently when people in several countries were faced with the threat of an epidemic. However, inoculation was not without its attendant risks. There were concerns that recipients might develop disseminated smallpox and spread it to others. Transmission of other diseases, such as syphilis, via the bloodborne route was also of concern.

Inoculation, hereafter referred to as variolation, was likely practiced in Africa, India, and China long before the 18th century, when it was introduced to Europe ( 9 ). In 1670, Circassian traders introduced variolation to the Turkish “Ottoman” Empire. Women from the Caucasus, who were in great demand in the Turkish sultan's harem in Istanbul because of their legendary beauty, were inoculated as children in parts of their bodies where scars would not be seen. These women must also have brought the practice of variolation to the court of the Sublime Porte ( 4 , 10 ).

Variolation came to Europe at the beginning of the 18th century with the arrival of travelers from Istanbul. In 1714, the Royal Society of London received a letter from Emanuel Timoni describing the technique of variolation, which he had witnessed in Istanbul. A similar letter was sent by Giacomo Pilarino in 1716. These reports described the practice of subcutaneous inoculation; however, they did not change the ways of the conservative English physicians.

It was the continued advocacy of the English aristocrat Lady Mary Wortley Montague (Figure ​ (Figure2 2 ) that was responsible for the introduction of variolation in England ( 10 ). In 1715, Lady Montague suffered from an episode of smallpox, which severely disfigured her beautiful face. Her 20-year-old brother died of the illness 18 months later. In 1717, Lady Montague's husband, Edward Wortley Montague, was appointed ambassador to the Sublime Porte. A few weeks after their arrival in Istanbul, Lady Montague wrote to her friend about the method of variolation used at the Ottoman court. Lady Montague was so determined to prevent the ravages of smallpox that she ordered the embassy surgeon, Charles Maitland, to inoculate her 5-year-old son. The inoculation procedure was performed in March 1718. Upon their return to London in April 1721, Lady Montague had Charles Maitland inoculate her 4-year-old daughter in the presence of physicians of the royal court.

Lady Mary Wortley Montague (1689–1762). Photo courtesy of the National Library of Medicine.

After these first professional variolation procedures, word of the practice spread to several members of the royal family ( 11 ). Charles Maitland was then granted the royal license to perform a trial of variolation on six prisoners in Newgate on August 9, 1721. The prisoners were granted the king's favor if they submitted to this experiment. Several court physicians, members of the Royal Society, and members of the College of Physicians observed the trial. All prisoners survived the experiment, and those exposed to smallpox later proved to be immune. In the months following this very first trial, Maitland repeated the experiment on orphaned children, again with success. Finally, on April 17, 1722, Maitland successfully treated the two daughters of the Princess of Wales. Not surprisingly, the procedure gained general acceptance after this last success.

THE SPREAD OF VARIOLATION

In Europe, where the medical profession was relatively organized, the new methods of variolation became known quickly among physicians. Since there was also a demand for protection against smallpox, physicians soon began the variolation procedure on a massive scale. Although 2% to 3% of variolated persons died from the disease, became the source of another epidemic, or suffered from diseases (e.g., tuberculosis and syphilis) transmitted by the procedure itself, variolation rapidly gained popularity among both aristocratic and common people in Europe. The case-fatality rate associated with variolation was 10 times lower than that associated with naturally occurring smallpox. In the 1750s more European princes died of smallpox, giving further impetus for the use of variolation ( 3 ). Among those variolated were Empress Marie-Therese of Austria and her children and grandchildren, Frederick II of Prussia, King Louis XVI of France and his children, and Catherine II of Russia and her son. King Frederick II of Prussia also inoculated all his soldiers. In fact, variolation was widely practiced in Europe until Jenner's discovery.

The regular practice of variolation reached the New World in 1721 ( 9 ). Under the guidance of the Rev. Cotton Mather (1663–1728) and Dr. Zabdiel Boylston (1679–1766), variolation became quite popular in the colonies. Mather, a graduate of Harvard College, was always very interested in science and medicine. When a ship from the West Indies carried persons sick with smallpox into Boston in 1721, an epidemic broke out in Boston and other parts of Massachusetts. Mather wrote a cautious letter recommending immediate variolation. However, he persuaded only Dr. Boylston. With Mather's support, Boylston immediately started a variolation program and continued to inoculate many volunteers, despite many adversaries in both the public and the medical community in Boston. As the disease spread, so did the controversy around Mather and Boylston ( 12 ). At the height of the epidemic, a bomb was thrown into Mather's house.

To make their point, Mather and Boylston used a statistical approach to compare the mortality rate of natural smallpox infection with that contracted by variolation. During the great epidemic of 1721, approximately half of Boston's 12,000 citizens contracted smallpox. The fatality rate for the naturally contracted disease was 14%, whereas Boylston and Mather reported a mortality rate of only 2% among variolated individuals ( 12 ). This may have been the first time that comparative analysis was used to evaluate a medical procedure.

During the decades following the 1721 epidemic in Boston, variolation became more widespread in the colonies of New England. In 1766, American soldiers under George Washington were unable to take Quebec from the British troops, apparently because of a smallpox epidemic that significantly reduced the number of healthy troops ( 13 ). The British soldiers were all variolated. By 1777, Washington had learned his lesson: all his soldiers were variolated before beginning new military operations ( 14 , 15 ). The success of variolation in the New World was not without effect on Europe. In fact, the rapid adoption of variolation in Europe can be directly traced to the efforts of Cotton Mather during the Boston smallpox epidemic in 1721. Although many British physicians remained skeptical even after Mather's success, the data he had published were eventually influential. Variolation was subsequently adopted in England and spread from there throughout Western Europe.

In 1757, an 8-year-old boy was inoculated with smallpox in Gloucester ( 4 ); he was one of thousands of children inoculated that year in England. The procedure was effective, as the boy developed a mild case of smallpox and was subsequently immune to the disease. His name was Edward Jenner.

EDWARD JENNER

Edward Jenner was born on May 17, 1749, in Berkeley, Gloucestershire, the son of the Rev. Stephen Jenner, vicar of Berkeley. Edward was orphaned at age 5 and went to live with his older brother. During his early school years, Edward developed a strong interest in science and nature that continued throughout his life. At age 13 he was apprenticed to a country surgeon and apothecary in Sodbury, near Bristol ( 16 ). The record shows that it was there that Jenner heard a dairymaid say, “I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face.” It fact, it was a common belief that dairymaids were in some way protected from smallpox.

In 1764, Jenner began his apprenticeship with George Harwicke. During these years, he acquired a sound knowledge of surgical and medical practice ( 10 ). Upon completion of this apprenticeship at the age of 21, Jenner went to London and became a student of John Hunter, who was on the staff of St. George's Hospital in London. Hunter was not only one of the most famous surgeons in England, but he was also a well-respected biologist, anatomist, and experimental scientist. The firm friendship that grew between Hunter and Jenner lasted until Hunter's death in 1793. Although Jenner already had a great interest in natural science, the experience during the 2 years with Hunter only increased his activities and curiosity. Jenner was so interested in natural science that he helped classify many species that Captain Cook brought back from his first voyage. In 1772, however, Jenner declined Cook's invitation to take part in the second voyage ( 4 ).

Jenner occupied himself with many matters. He studied geology and carried out experiments on human blood ( 17 ). In 1784, after public demonstrations of hot air and hydrogen balloons by Joseph M. Montgolfier in France during the preceding year, Jenner built and twice launched his own hydrogen balloon. It flew 12 miles. Following Hunter's suggestions, Jenner conducted a particular study of the cuckoo. The final version of Jenner's paper was published in 1788 and included the original observation that it is the cuckoo hatchling that evicts the eggs and chicks of the foster parents from the nest ( 17 , 18 ). For this remarkable work, Jenner was elected a fellow of the Royal Society. However, many naturalists in England dismissed his work as pure nonsense. For more than a century, antivaccinationists used the supposed defects of the cuckoo study to cast doubt on Jenner's other work. Jenner was finally vindicated in 1921 when photography confirmed his observation ( 19 ). At any rate, it is apparent that Jenner had a lifelong interest in natural sciences. His last work, published posthumously, was on the migration of birds.

In addition to his training and experience in biology, Jenner made great progress in clinical surgery while studying with John Hunter in London. Jenner devised an improved method for preparing a medicine known as tartar emetic (potassium antimony tartrate). In 1773, at the end of 2 years with John Hunter, Jenner returned to Berkeley to practice medicine. There he enjoyed substantial success, for he was capable, skillful, and popular. In addition to the practice of medicine, he joined two local medical groups for the promotion of medical knowledge and continued to write occasional medical papers ( 4 , 18 ). He also played the violin in a musical club and wrote light verse and poetry. As a natural scientist, he continued to make many observations on birds and the hibernation of hedgehogs and collected many specimens for John Hunter in London.

While Jenner's interest in the protective effects of cowpox began during his apprenticeship with George Harwicke, it was 1796 before he made the first step in the long process whereby smallpox, the scourge of mankind, would be totally eradicated. For many years, he had heard the tales that dairymaids were protected from smallpox naturally after having suffered from cowpox. Pondering this, Jenner concluded that cowpox not only protected against smallpox but also could be transmitted from one person to another as a deliberate mechanism of protection. In May 1796, Edward Jenner found a young dairymaid, Sarah Nelms, who had fresh cowpox lesions on her hands and arms (Figure ​ (Figure3 3 ) . On May 14, 1796, using matter from Nelms' lesions, he inoculated an 8-year-old boy, James Phipps. Subsequently, the boy developed mild fever and discomfort in the axillae. Nine days after the procedure he felt cold and had lost his appetite, but on the next day he was much better. In July 1796, Jenner inoculated the boy again, this time with matter from a fresh smallpox lesion. No disease developed, and Jenner concluded that protection was complete ( 10 ).

The hand of Sarah Nelms. Photo courtesy of the National Library of Medicine.

In 1797, Jenner sent a short communication to the Royal Society describing his experiment and observations. However, the paper was rejected. Then in 1798, having added a few more cases to his initial experiment, Jenner privately published a small booklet entitled An Inquiry into the Causes and Effects of the Variolae Vaccinae, a disease discovered in some of the western counties of England, particularly Gloucestershire and Known by the Name of Cow Pox ( 18 , 10 ). The Latin word for cow is vacca , and cowpox is vaccinia ; Jenner decided to call this new procedure vaccination . The 1798 publication had three parts. In the first part Jenner presented his view regarding the origin of cowpox as a disease of horses transmitted to cows. The theory was discredited during Jenner's lifetime. He then presented the hypothesis that infection with cowpox protects against subsequent infection with smallpox. The second part contained the critical observations relevant to testing the hypothesis. The third part was a lengthy discussion, in part polemical, of the findings and a variety of issues related to smallpox. The publication of the Inquiry was met with a mixed reaction in the medical community.

Jenner went to London in search of volunteers for vaccination. However, after 3 months he had found none. In London, vaccination became popular through the activities of others, particularly the surgeon Henry Cline, to whom Jenner had given some of the inoculant ( 4 ). Later in 1799, Drs. George Pearson and William Woodville began to support vaccination among their patients. Jenner conducted a nationwide survey in search of proof of resistance to smallpox or to variolation among persons who had cowpox. The results of this survey confirmed his theory. Despite errors, many controversies, and chicanery, the use of vaccination spread rapidly in England, and by the year 1800, it had also reached most European countries ( 10 ).

Although sometimes embarrassed by a lack of supply, Jenner sent vaccine to his medical acquaintances and to anyone else who requested it. After introducing cowpox inoculation in their own districts, many recipients passed the vaccine on to others. Dr. John Haygarth (of Bath, Somerset) received the vaccine from Edward Jenner in 1800 and sent some of the material to Benjamin Waterhouse, professor of physics at Harvard University. Waterhouse introduced vaccination in New England and then persuaded Thomas Jefferson to try it in Virginia. Waterhouse received great support from Jefferson, who appointed him vaccine agent in the National Vaccine Institute, an organization set up to implement a national vaccination program in the United States ( 20 ).

Although he received worldwide recognition and many honors, Jenner made no attempt to enrich himself through his discovery. He actually devoted so much time to the cause of vaccination that his private practice and his personal affairs suffered severely. The extraordinary value of vaccination was publicly acknowledged in England, when in 1802 the British Parliament granted Edward Jenner the sum of £10,000. Five years later the Parliament awarded him £20,000 more. However, he not only received honors but also found himself subjected to attacks and ridicule. Despite all this, he continued his activities on behalf of the vaccination program. Gradually, vaccination replaced variolation, which became prohibited in England in 1840.

Jenner married in 1788 and fathered four children. The family lived in the Chantry House, which became the Jenner Museum in 1985. Jenner built a one-room hut in the garden, which he called the “Temple of Vaccinia” (Figure ​ (Figure4 4 ) , where he vaccinated the poor for free ( 10 , 17 ). After a decade of being honored and reviled in more or less equal measure, he gradually withdrew from public life and returned to the practice of country medicine in Berkeley. In 1810, his oldest son, Edward, died of tuberculosis. His sister Mary died the same year and his sister Anne 2 years later. In 1815, his wife, Catherine, died of tuberculosis ( 17 ). Sorrows crowded in on him, and he withdrew even further from public life. In 1820, Jenner had a stroke from which he recovered. On January 23, 1823, he visited his last patient, a dying friend. The next morning Jenner failed to appear for breakfast; later that day he was found in his study. He had had a massive stroke. Edward Jenner died during the early morning hours of Sunday, January 26, 1823. He was laid to rest with his parents, his wife, and his son near the altar of the Berkeley church.

The Temple of Vaccinia. Photo courtesy of the Jenner Museum, Berkeley, Gloucestershire, England.

Jenner's work represented the first scientific attempt to control an infectious disease by the deliberate use of vaccination. Strictly speaking, he did not discover vaccination but was the first person to confer scientific status on the procedure and to pursue its scientific investigation. During the past years, there has been a growing recognition of Benjamin Jesty (1737–1816) as the first to vaccinate against smallpox ( 21 ). When smallpox was present in Jesty's locality in 1774, he was determined to protect the life of his family. Jesty used material from udders of cattle that he knew had cowpox and transferred the material with a small lancet to the arms of his wife and two boys. The trio of vaccinees remained free of smallpox, although they were exposed on numerous occasions in later life. Benjamin Jesty was neither the first nor the last to experiment with vaccination. In fact, the use of smallpox and cowpox was widely known among the country physicians in the dairy counties of 18th-century England. However, the recognition of these facts should not diminish our view of Jenner's accomplishments. It was his relentless promotion and devoted research of vaccination that changed the way medicine was practiced.

Late in the 19th century, it was realized that vaccination did not confer lifelong immunity and that subsequent revaccination was necessary. The mortality from smallpox had declined, but the epidemics showed that the disease was still not under control. In the 1950s a number of control measures were implemented, and smallpox was eradicated in many areas in Europe and North America. The process of worldwide eradication of smallpox was set in motion when the World Health Assembly received a report in 1958 of the catastrophic consequences of smallpox in 63 countries (Figure ​ (Figure5 5 ) . In 1967, a global campaign was begun under the guardianship of the World Health Organization and finally succeeded in the eradication of smallpox in 1977. On May 8, 1980, the World Health Assembly announced that the world was free of smallpox and recommended that all countries cease vaccination: “The world and all its people have won freedom from smallpox, which was the most devastating disease sweeping in epidemic form through many countries since earliest times, leaving death, blindness and disfigurement in its wake” ( 22 ).

Smallpox in India, 1970s. Photo courtesy of the World Health Organization.

Scientific advances during the two centuries since Edward Jenner performed his first vaccination on James Phipps have proved him to be more right than wrong. The germ theory of disease, the discovery and study of viruses, and the understanding of modern immunology tended to support his main conclusions. The discovery and promotion of vaccination enabled the eradication of smallpox: this is Edward Jenner's ultimate vindication and memorial.

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• Solar Eclipse 2024

What the World Has Learned From Past Eclipses

C louds scudded over the small volcanic island of Principe, off the western coast of Africa, on the afternoon of May 29, 1919. Arthur Eddington, director of the Cambridge Observatory in the U.K., waited for the Sun to emerge. The remains of a morning thunderstorm could ruin everything.

The island was about to experience the rare and overwhelming sight of a total solar eclipse. For six minutes, the longest eclipse since 1416, the Moon would completely block the face of the Sun, pulling a curtain of darkness over a thin stripe of Earth. Eddington traveled into the eclipse path to try and prove one of the most consequential ideas of his age: Albert Einstein’s new theory of general relativity.

Eddington, a physicist, was one of the few people at the time who understood the theory, which Einstein proposed in 1915. But many other scientists were stymied by the bizarre idea that gravity is not a mutual attraction, but a warping of spacetime. Light itself would be subject to this warping, too. So an eclipse would be the best way to prove whether the theory was true, because with the Sun’s light blocked by the Moon, astronomers would be able to see whether the Sun’s gravity bent the light of distant stars behind it.

Two teams of astronomers boarded ships steaming from Liverpool, England, in March 1919 to watch the eclipse and take the measure of the stars. Eddington and his team went to Principe, and another team led by Frank Dyson of the Greenwich Observatory went to Sobral, Brazil.

Totality, the complete obscuration of the Sun, would be at 2:13 local time in Principe. Moments before the Moon slid in front of the Sun, the clouds finally began breaking up. For a moment, it was totally clear. Eddington and his group hastily captured images of a star cluster found near the Sun that day, called the Hyades, found in the constellation of Taurus. The astronomers were using the best astronomical technology of the time, photographic plates, which are large exposures taken on glass instead of film. Stars appeared on seven of the plates, and solar “prominences,” filaments of gas streaming from the Sun, appeared on others.

Eddington wanted to stay in Principe to measure the Hyades when there was no eclipse, but a ship workers’ strike made him leave early. Later, Eddington and Dyson both compared the glass plates taken during the eclipse to other glass plates captured of the Hyades in a different part of the sky, when there was no eclipse. On the images from Eddington’s and Dyson’s expeditions, the stars were not aligned. The 40-year-old Einstein was right.

“Lights All Askew In the Heavens,” the New York Times proclaimed when the scientific papers were published. The eclipse was the key to the discovery—as so many solar eclipses before and since have illuminated new findings about our universe.

To understand why Eddington and Dyson traveled such distances to watch the eclipse, we need to talk about gravity.

Since at least the days of Isaac Newton, who wrote in 1687, scientists thought gravity was a simple force of mutual attraction. Newton proposed that every object in the universe attracts every other object in the universe, and that the strength of this attraction is related to the size of the objects and the distances among them. This is mostly true, actually, but it’s a little more nuanced than that.

On much larger scales, like among black holes or galaxy clusters, Newtonian gravity falls short. It also can’t accurately account for the movement of large objects that are close together, such as how the orbit of Mercury is affected by its proximity the Sun.

Albert Einstein’s most consequential breakthrough solved these problems. General relativity holds that gravity is not really an invisible force of mutual attraction, but a distortion. Rather than some kind of mutual tug-of-war, large objects like the Sun and other stars respond relative to each other because the space they are in has been altered. Their mass is so great that they bend the fabric of space and time around themselves.

Read More: 10 Surprising Facts About the 2024 Solar Eclipse

This was a weird concept, and many scientists thought Einstein’s ideas and equations were ridiculous. But others thought it sounded reasonable. Einstein and others knew that if the theory was correct, and the fabric of reality is bending around large objects, then light itself would have to follow that bend. The light of a star in the great distance, for instance, would seem to curve around a large object in front of it, nearer to us—like our Sun. But normally, it’s impossible to study stars behind the Sun to measure this effect. Enter an eclipse.

Einstein’s theory gives an equation for how much the Sun’s gravity would displace the images of background stars. Newton’s theory predicts only half that amount of displacement.

Eddington and Dyson measured the Hyades cluster because it contains many stars; the more stars to distort, the better the comparison. Both teams of scientists encountered strange political and natural obstacles in making the discovery, which are chronicled beautifully in the book No Shadow of a Doubt: The 1919 Eclipse That Confirmed Einstein's Theory of Relativity , by the physicist Daniel Kennefick. But the confirmation of Einstein’s ideas was worth it. Eddington said as much in a letter to his mother: “The one good plate that I measured gave a result agreeing with Einstein,” he wrote , “and I think I have got a little confirmation from a second plate.”

The Eddington-Dyson experiments were hardly the first time scientists used eclipses to make profound new discoveries. The idea dates to the beginnings of human civilization.

Careful records of lunar and solar eclipses are one of the greatest legacies of ancient Babylon. Astronomers—or astrologers, really, but the goal was the same—were able to predict both lunar and solar eclipses with impressive accuracy. They worked out what we now call the Saros Cycle, a repeating period of 18 years, 11 days, and 8 hours in which eclipses appear to repeat. One Saros cycle is equal to 223 synodic months, which is the time it takes the Moon to return to the same phase as seen from Earth. They also figured out, though may not have understood it completely, the geometry that enables eclipses to happen.

The path we trace around the Sun is called the ecliptic. Our planet’s axis is tilted with respect to the ecliptic plane, which is why we have seasons, and why the other celestial bodies seem to cross the same general path in our sky.

As the Moon goes around Earth, it, too, crosses the plane of the ecliptic twice in a year. The ascending node is where the Moon moves into the northern ecliptic. The descending node is where the Moon enters the southern ecliptic. When the Moon crosses a node, a total solar eclipse can happen. Ancient astronomers were aware of these points in the sky, and by the apex of Babylonian civilization, they were very good at predicting when eclipses would occur.

Two and a half millennia later, in 2016, astronomers used these same ancient records to measure the change in the rate at which Earth’s rotation is slowing—which is to say, the amount by which are days are lengthening, over thousands of years.

By the middle of the 19 th century, scientific discoveries came at a frenetic pace, and eclipses powered many of them. In October 1868, two astronomers, Pierre Jules César Janssen and Joseph Norman Lockyer, separately measured the colors of sunlight during a total eclipse. Each found evidence of an unknown element, indicating a new discovery: Helium, named for the Greek god of the Sun. In another eclipse in 1869, astronomers found convincing evidence of another new element, which they nicknamed coronium—before learning a few decades later that it was not a new element, but highly ionized iron, indicating that the Sun’s atmosphere is exceptionally, bizarrely hot. This oddity led to the prediction, in the 1950s, of a continual outflow that we now call the solar wind.

And during solar eclipses between 1878 and 1908, astronomers searched in vain for a proposed extra planet within the orbit of Mercury. Provisionally named Vulcan, this planet was thought to exist because Newtonian gravity could not fully describe Mercury’s strange orbit. The matter of the innermost planet’s path was settled, finally, in 1915, when Einstein used general relativity equations to explain it.

Many eclipse expeditions were intended to learn something new, or to prove an idea right—or wrong. But many of these discoveries have major practical effects on us. Understanding the Sun, and why its atmosphere gets so hot, can help us predict solar outbursts that could disrupt the power grid and communications satellites. Understanding gravity, at all scales, allows us to know and to navigate the cosmos.

GPS satellites, for instance, provide accurate measurements down to inches on Earth. Relativity equations account for the effects of the Earth’s gravity and the distances between the satellites and their receivers on the ground. Special relativity holds that the clocks on satellites, which experience weaker gravity, seem to run slower than clocks under the stronger force of gravity on Earth. From the point of view of the satellite, Earth clocks seem to run faster. We can use different satellites in different positions, and different ground stations, to accurately triangulate our positions on Earth down to inches. Without those calculations, GPS satellites would be far less precise.

This year, scientists fanned out across North America and in the skies above it will continue the legacy of eclipse science. Scientists from NASA and several universities and other research institutions will study Earth’s atmosphere; the Sun’s atmosphere; the Sun’s magnetic fields; and the Sun’s atmospheric outbursts, called coronal mass ejections.

When you look up at the Sun and Moon on the eclipse , the Moon’s day — or just observe its shadow darkening the ground beneath the clouds, which seems more likely — think about all the discoveries still yet waiting to happen, just behind the shadow of the Moon.

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Why Taiwan Was So Prepared for a Powerful Earthquake

Decades of learning from disasters, tightening building codes and increasing public awareness may have helped its people better weather strong quakes.

Search-and-rescue teams recover a body from a leaning building in Hualien, Taiwan. Thanks to improvements in building codes after past earthquakes, many structures withstood Wednesday’s quake. Credit...

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By Chris Buckley ,  Meaghan Tobin and Siyi Zhao

Photographs by Lam Yik Fei

Chris Buckley reported from the city of Hualien, Meaghan Tobin from Taipei, in Taiwan.

• April 4, 2024

When the largest earthquake in Taiwan in half a century struck off its east coast, the buildings in the closest city, Hualien, swayed and rocked. As more than 300 aftershocks rocked the island over the next 24 hours to Thursday morning, the buildings shook again and again.

But for the most part, they stood.

Even the two buildings that suffered the most damage remained largely intact, allowing residents to climb to safety out the windows of upper stories. One of them, the rounded, red brick Uranus Building, which leaned precariously after its first floors collapsed, was mostly drawing curious onlookers.

The building is a reminder of how much Taiwan has prepared for disasters like the magnitude-7.4 earthquake that jolted the island on Wednesday. Perhaps because of improvements in building codes, greater public awareness and highly trained search-and-rescue operations — and, likely, a dose of good luck — the casualty figures were relatively low. By Thursday, 10 people had died and more than 1,000 others were injured. Several dozen were missing.

“Similar level earthquakes in other societies have killed far more people,” said Daniel Aldrich , a director of the Global Resilience Institute at Northeastern University. Of Taiwan, he added: “And most of these deaths, it seems, have come from rock slides and boulders, rather than building collapses.”

Across the island, rail traffic had resumed by Thursday, including trains to Hualien. Workers who had been stuck in a rock quarry were lifted out by helicopter. Roads were slowly being repaired. Hundreds of people were stranded at a hotel near a national park because of a blocked road, but they were visited by rescuers and medics.

On Thursday in Hualien city, the area around the Uranus Building was sealed off, while construction workers tried to prevent the leaning structure from toppling completely. First they placed three-legged concrete blocks that resembled giant Lego pieces in front of the building, and then they piled dirt and rocks on top of those blocks with excavators.

“We came to see for ourselves how serious it was, why it has tilted,” said Chang Mei-chu, 66, a retiree who rode a scooter with her husband Lai Yung-chi, 72, to the building on Thursday. Mr. Lai said he was a retired builder who used to install power and water pipes in buildings, and so he knew about building standards. The couple’s apartment, near Hualien’s train station, had not been badly damaged, he said.

“I wasn’t worried about our building, because I know they paid attention to earthquake resistance when building it. I watched them pour the cement to make sure,” Mr. Lai said. “There have been improvements. After each earthquake, they raise the standards some more.”

It was possible to walk for city blocks without seeing clear signs of the powerful earthquake. Many buildings remained intact, some of them old and weather-worn; others modern, multistory concrete-and-glass structures. Shops were open, selling coffee, ice cream and betel nuts. Next to the Uranus Building, a popular night market with food stalls offering fried seafood, dumplings and sweets was up and running by Thursday evening.

Earthquakes are unavoidable in Taiwan, which sits on multiple active faults. Decades of work learning from other disasters, implementing strict building codes and increasing public awareness have gone into helping its people weather frequent strong quakes.

Not far from the Uranus Building, for example, officials had inspected a building with cracked pillars and concluded that it was dangerous to stay in. Residents were given 15 minutes to dash inside and retrieve as many belongings as they could. Some ran out with computers, while others threw bags of clothes out of windows onto the street, which was also still littered with broken glass and cement fragments from the quake.

One of its residents, Chen Ching-ming, a preacher at a church next door, said he thought the building might be torn down. He was able to salvage a TV and some bedding, which now sat on the sidewalk, and was preparing to go back in for more. “I’ll lose a lot of valuable things — a fridge, a microwave, a washing machine,” he said. “All gone.”

Requirements for earthquake resistance have been built into Taiwan’s building codes since 1974. In the decades since, the writers of Taiwan’s building code also applied lessons learned from other major earthquakes around the world, including in Mexico and Los Angeles, to strengthen Taiwan’s code.

After more than 2,400 people were killed and at least 10,000 others injured during the Chi-Chi quake of 1999, thousands of buildings built before the quake were reviewed and reinforced. After another strong quake in 2018 in Hualien, the government ordered a new round of building inspections. Since then, multiple updates to the building code have been released.

“We have retrofitted more than 10,000 school buildings in the last 20 years,” said Chung-Che Chou, the director general of the National Center for Research on Earthquake Engineering in Taipei.

The government had also helped reinforce private apartment buildings over the past six years by adding new steel braces and increasing column and beam sizes, Dr. Chou said. Not far from the buildings that partially collapsed in Hualien, some of the older buildings that had been retrofitted in this way survived Wednesday’s quake, he said.

The result of all this is that even Taiwan’s tallest skyscrapers can withstand regular seismic jolts. The capital city’s most iconic building, Taipei 101, once the tallest building in the world, was engineered to stand through typhoon winds and frequent quakes. Still, some experts say that more needs to be done to either strengthen or demolish structures that don’t meet standards, and such calls have grown louder in the wake of the latest earthquake.

Taiwan has another major reason to protect its infrastructure: It is home to the majority of production for the Taiwan Semiconductor Manufacturing Company, the world’s largest maker of advanced computer chips. The supply chain for electronics from smartphones to cars to fighter jets rests on the output of TSMC’s factories, which make these chips in facilities that cost billions of dollars to build.

The 1999 quake also prompted TSMC to take extra steps to insulate its factories from earthquake damage. The company made major structural adjustments and adopted new technologies like early warning systems. When another large quake struck the southern city of Kaohsiung in February 2016, TSMC’s two nearby factories survived without structural damage.

Taiwan has made strides in its response to disasters, experts say. In the first 24 hours after the quake, rescuers freed hundreds of people who were trapped in cars in between rockfalls on the highway and stranded on mountain ledges in rock quarries.

“After years of hard work on capacity building, the overall performance of the island has improved significantly,” said Bruce Wong, an emergency management consultant in Hong Kong. Taiwan’s rescue teams have come to specialize in complex efforts, he said, and it has also been able to tap the skills of trained volunteers.

Taiwan’s resilience also stems from a strong civil society that is involved in public preparedness for disasters.

Ou Chi-hu, a member of a group of Taiwanese military veterans, was helping distribute water and other supplies at a school that was serving as a shelter for displaced residents in Hualien. He said that people had learned from the 1999 earthquake how to be more prepared.

“They know to shelter in a corner of the room or somewhere else safer,” he said. Many residents also keep a bag of essentials next to their beds, and own fire extinguishers, he added.

Around him, a dozen or so other charities and groups were offering residents food, money, counseling and childcare. The Tzu Chi Foundation, a large Taiwanese Buddhist charity, provided tents for families to use inside the school hall so they could have more privacy. Huang Yu-chi, a disaster relief manager with the foundation, said nonprofits had learned from earlier disasters.

“Now we’re more systematic and have a better idea of disaster prevention,” Mr. Huang said.

Mike Ives contributed reporting from Seoul.

Chris Buckley , the chief China correspondent for The Times, reports on China and Taiwan from Taipei, focused on politics, social change and security and military issues. More about Chris Buckley

Meaghan Tobin is a technology correspondent for The Times based in Taipei, covering business and tech stories in Asia with a focus on China. More about Meaghan Tobin

Siyi Zhao is a reporter and researcher who covers news in mainland China for The Times in Seoul. More about Siyi Zhao

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