Smallpox: The Birth of Biological Warfare and the First Vaccine

Smallpox is one of the most prolific viruses ever known to mankind. Thanks to eradication in 1977, it is not something most of us have had to deal with in our lifetime. However, there was a time when contracting smallpox was an unavoidable part of life for everyone. Smallpox is caused by the variola virus and leads to lesions and pustules on the skin and internal organs. These lesions erode and destroy tissue, which results in a 30% mortality rate for those effected. Those who survive are inevitably scared for life. Before there were effective vaccines for smallpox, the scars were something that everyone had to live with (National Geographic). Imagine that many classical paintings of beautiful and handsome people from a few hundred years ago and earlier glossed over the fact that every subject was severely scarred. This was simply part of human life.

Scientists believe that the disease probably dates back to 10,000 BC and came to us as a zoonosis (from animal populations). Since it would require a population of at least a couple hundred thousand people to catch hold, we believe that it effected the human population shortly after the agricultural boom and proliferated in the denser populations that it provided. The first known case of the disease is Ramses V of Egypt who died in 1157 BC. When his mummy was excavated lesions comparable to modern smallpox were spread all over its skin.

After almost a thousand years of variolation and vaccination attempts across the globe, the WHO was able to officially eradicate smallpox in 1980. There was a call to send in remaining specimens of the virus from labs all over the world and only two samples currently exist in maximum security labs in the US and Russia. There is a debate as to whether or not these vials should be destroyed, and whether or not smallpox still poses a threat to society: a world in which the entire population has absolutely no immunity to an allegedly "extinct" virus.

This paper discusses the biological mechanisms behind and the historical consequences of the smallpox virus. It will explore the controversial process of variolation and the scientific discovery of the world's first vaccination. While both processes were unsettling at the time, they were the keys to enabling humanity to conquer one of the worst scourges it has ever faced. While vaccination plays such an important role in our lives today, the history of where it all began is an interesting story which illustrates all of the challenges that science faces on the road to progress.

Smallpox, or Variola Major, is a spiky, brick shaped virus that is extremely easy to spread between humans. It is not spread to or from animals or insects. Most animals have their own form of the pox. This fact eventually played an important role in the cure of smallpox. Not everyone exposed to the virus will contract it, but most will. The highly contagious nature of the virus comes down to the fact that it is airborne, this also makes it a uniquely dangerous potential biological weapon. The virus generally enters the body through the nose, and gets into cells in the lining of the throat (WHO). There is a ten day incubation period in which one shows no sign of illness, yet is infectious. This makes the disease increasingly easy to spread because its contagious victims are able to walk around amongst other people completely fine for a week and a half before even realizing they are sick. The aforementioned infected cells explode and quickly infect other cells in the body. The high mortality rate is due to the fact that the virus eats away at internal structures. Many victims drown in their own liquids. After about a month, the blisters fall off in deep scabs which leave the victim scarred for life with pits. The scabs still carry live virus and the victim's blood holds onto it as well. All bedding - everything the person contacted - needs to be burned. The scientific paper, “Does Smallpox Still Pose a Threat” details the mechanism of the smallpox virus.

“On exposure, the virus lodges on the oropharyngeal mucosa and subsequently migrates to regional lymph nodes. Two to 3 days after infection an asymptomatic viremia develops, followed by viral multiplication in the spleen, bone marrow and lymph nodes. The virus, packaged in leukocytes, then localizes in small blood vessels of the dermis and beneath the oral and pharyngeal mucosa. Infected macrophages migrate to the epidermis, causing edema, necrosis and splitting of the dermis. A maculopapular rash erupts and progresses to vesicles and then pustules. Pock marks result from the destruction of sebaceous glands, followed by the shrinking of granulation tissue; blindness can result from scarring in the conjunctiva. The lesions rarely become secondarily infected. Death, which typically occurs in the second week of illness, likely results from the toxemia produced by circulating immune complexes and soluble viral antigen" (Wier, 2013).

This harrowing biological account gives an idea of the extremely painful death and illness that humanity was once regularly exposed to. One also has an understanding of why we went to great lengths throughout history to fight it.

Smallpox eradicated the Incas and Aztecs after the onset of the Spanish and Portuguese conquistadors. The native populations in the Americas were particularly susceptible to the virus and saw 70-90% mortality rates. These great warrior societies proved impossible to beat in battle. However, some conquistadors carried smallpox, and so within a few short years entire societies were destroyed. In the French and Indian war smallpox was used as the first purposeful biological weapon. Sir Jeffrey Amherst of the British army suggested deliberately spreading it to Native American tribes. After distributing two infected blankets to a hospital as an alleged "donation" a massive epidemic began to wipe out the native American population in a matter of months. Smallpox, is responsible for wiping out entire populations across the entire “New World" (History of Vaccines, College of Physicians).

The first accounts of inoculation date back to 1,000 BC when the son of a Chinese statesman was inoculated. This was probably done by blowing dried smallpox scabs into his nose, or by cutting his skin and exposing it to some liquid from a live smallpox pustule. This form of inoculation (interchangeably referred to as variolation) is not exactly a vaccine or cure. However, if someone is inoculated like this, then they have a good chance of surviving the milder form of smallpox which will inevitably ensue from the inoculation. As opposed to a 30% mortality rate, inoculated patients suffered a 2-4% mortality rate. Inoculation was popular in Asia and was not known about in Europe until the 1700s. In the 18th century, 400,000 people died annually of the virus, and a third of those who contracted it were blinded by what was then referred to as "the speckled monster" (History of Vaccines, College of Physicians).

In 1718, before variolation was popular in Europe, Lady Mary Montegue of England visited Turkey, where her husband had been severely disfigured by the virus. There she witnessed inoculation - which was completely foreign to Europeans - and had the procedure performed on her six year old son Edward. She advocated the procedure in England where people were understandably skeptical. In 1721 she had her one year old daughter inoculated, and this was the first instance of European inoculation. As mentioned 2-3% of those inoculated did die, and inoculated individuals were able to spread the disease onto others. Lady Mary came under a lot of fire for advocacy of the procedure. It is understandable that people would be suspicious of purposefully infecting themselves with the world's most horrendous known pathogen. But keep in mind that everyone was bound to be exposed to it eventually, and those mortality rates soared compared to variolation mortality rates (Smallpox Full Documentary, 2014).

Despite a suspicious population, further outbreaks in the American colonies consistently resulted in lower mortality rates with variolation as opposed to natural exposure. Benjamin Franklin eventually became an advocate for the procedure after his son died of the disease, and eventually even European populations accepted variolation as the only reasonable alternative.

A great breakthrough came in 1770 when Edward Jenner, and English physician, learned from a milkmaid that she believed herself immune to smallpox due to her exposure to cowpox. As earlier mentioned, animals have their own distinct varieties of the pox, and cowpox is a much milder form of the virus. Milkmaids would acquire the cowpox disease from cows, which was then expressed as small pustules on their hands which would go away shortly without serious or lasting symptoms. Interestingly enough, milkmaids never got smallpox (Riedel, 2005)

Jenner, who was a passionate biologist deeply interested in the sciences, took a wild (although educated) guess that exposing someone to cowpox could render them immune to smallpox. He put his hypothesis into action by experimenting on an eight year old boy. The experiment that followed is extremely controversial by today's ethical standards, however, it resulted in the birth of the first vaccine. Jenner's first step was to select a child. The boy had his skin scratched, and some liquid from a cowpox pustule was inserted. The boy shortly fell ill for about 10 days, although the illness was not extreme. Once the boy had recovered, the child had his arm scratched once again, only this time living smallpox was inserted. Fortunately for the child, he did not acquire the virus, as he was indeed immune to smallpox due to his vaccination. The word vacca is cow in latin, while vaccinia is cowpox. Thus the first vaccine was born. Jenner was not the first person to attempt this particular type of vaccination, however, he was the first person to present it to the medical community and to go through scientific venues and methodology in order to actually show the world its capabilities (Riedel, 2005).

Jenner spent the rest of his life advocating for the vaccine. He was often ridiculed and his first scientific paper on the matter was actually rejected. He was unsuccessful in popularizing the vaccine himself, but it caught on with other doctors and scientist of the day who ultimately proliferated it to wider society. While the vaccine did not prove to change the world and smallpox remained virulent in many parts of it, the development of this first vaccine was a huge first step in defeating the spotted monster. It wasn't until 200 years later that small pox would ultimately be eradicated by an extremely efficient world wide vaccination scheme executed by the WHO. This fascinating story is discussed in detail in part two of this article. However, it is interesting to see where the early, and sometimes forgotten, roots of vaccination began. The journey was not always sound or ethical, and humanity literally faced over a thousand years of trial and error in understanding how to cope with this disease, but these first steps allowed us to eventually be successful in beating the plague that followed humanity throughout history and once had the power to destroy entire civilizations.

Sources:

Weir, Erica. "Does Smallpox Still Pose a Threat?" (n.d.): n. pag. CMAJ: Canadian Medical Association Journal. U.S. National Library of Medicine, 2013. Web.

"Smallpox, Smallpox Information, Infection Facts, News, Photos -- National Geographic." Editorial. n.d.: n. pag. National Geographic.

"History of Smallpox." History of Vaccines RSS. College of Physicians Philadelphia, n.d.

Riedel Stefan. "Edward Jenner and the History of Smallpox and Vaccination."US National Library of Medicine. N.p., Jan. 2005.

"Frequently Asked Questions and Answers on Smallpox."WHO. N.p., n.d.