International scientific collaboration makes use of the collective experiences, knowledge, and intellect of diverse nations. Through shared knowledge and combined efforts, it pioneers breakthroughs unattainable within the confines of solitary endeavors, propelling innovation to unprecedented heights. One clear instance exemplifying the power of international collaboration is demonstrated in the concerted effort of smallpox eradication.

Smallpox is an infectious disease that had plagued humanity for nearly 3000 years1. It was caused by the variola virus, and clinically manifested as a progressive skin rash to result in overwhelming viremia and a prolonged immune response that eventually contributed to the death of 30% of infected individuals1. The severity of this disease can be demonstrated by examination of the 20th century alone, in which a minimum estimate of 300 million people died 1. The global transmission of smallpox is largely attributed to the rapid expansion of international trade throughout the 13th – 18th centuries during which period smallpox became a pandemic and required massive eradication efforts1.

Prior to the 19th century, variolation was the primary method used to control smallpox1. This involved inhalation of smallpox scab material by a healthy, uninfected individual in hopes of inducing a mild but protective infection1. Although the origins of variolation remain poorly characterized, evidence suggests that it has roots in China and/or India, and later was adopted by the European subcontinent2. Despite its rudimentary nature, variolation decreased the overall mortality of the contracted disease from 30% to 2%1.  The standard of care did not change from variolation until 1796, during which an English doctor, Edward Jenner, noticed that milkmaids who had been infected with cowpox were protected from smallpox1. He postulated that cowpox may be of a similar nature to smallpox, and that exposure to cowpox can protect individuals from smallpox-associated death1. To test his hypothesis, Jenner took material from a cowpox pustule derived from an infected milkmaid’s arm and inoculated it into the arm of James Phipps, a 9-year-old boy1. Months later, Jenner exposed the boy multiple times to the variola virus, during which the boy never developed smallpox1. Jenner later published his results in what would become one of the first modern scientific publications in immunology. Jenner’s work on vaccination became widely accepted in Europe and was published in all of the major European languages3.

Two years following Jenner’s publication, Dr. John Clinch subsequently introduced Jenner’s vaccine to North America in Trinity, Newfoundland, Canada4. Similar efforts for vaccine administration were seen in the United States of America, in which the first vaccine was administered in 18005. Within the first decade of the 19th century, smallpox vaccination was routine in Europe and the United States6. Similarly in 1804, Francisco Javier de Balmis and his deputy José Salvany introduced the vaccine throughout the Spanish Empire in South America and Southeast Asia7

Despite such early collaborative efforts to spread vaccination throughout Europe, the Americas and Asia, and vaccination becoming mandatory in various regions, total eradication of smallpox was difficult to achieve. This was primarily due to concerns of infections occurring from vaccine contaminants and arm-to-arm vaccination strategies8. Thus, the WHO launched the global smallpox eradication program1. However, this initiative struggled with lack of funding and acceptance by some countries resulting in regular outbreaks occurring in South America, Asia, and Africa 1. The main identifiable issue was the lack of vaccine storage, as there had not yet been a streamlined method of storing vaccine doses for prolonged periods resulting in loss of vaccine efficacy following shipment1.

In the 1950s, an English microbiologist named Leslie Collier discovered that the addition of phenol and peptone to the liquid vaccine prevented bacterial contaminants and protected the virus particles from the freeze-dry process9. The process developed by Collier increased the efficacy of the dried vaccine following prolonged storage, which allowed it to be transported to and administered in tropical areas and remote communities9. In 1967, the WHO intensified the smallpox eradication program by using Collier’s vaccine storage method, employed more aggressive mass vaccination campaigns, and established case surveillance systems throughout the world9.

The efforts exerted by this intensified smallpox eradication program were further enforced by an agreement between the Soviet Union and the United States of America, whereby the Soviet Union purchased freeze-dried smallpox vaccines on behalf of Eastern Europe, China, and India10. Furthermore, in a concerted effort, America, Britain, Canada, Cuba, France, and the Soviet Union freely gave stored vaccines  to the WHO to distribute to countries with regular smallpox outbreaks10. In addition, the adoption of knowledge and technical resources by countries in Africa, Asia, and South America resulted in local manufacturing of vaccine supplies10. Through this concerted worldwide effort, the last case of naturally acquired smallpox infection was Ali Maalin from Somalia, in 19771. He was isolated by the local Somalian smallpox eradication team led by Jason Weisfeld from the American Centre for Disease Control, and Karl Markvart from Czechoslovakia11. Ali Maalin made a full recovery following treatment1. The world was declared free of smallpox on May 8th, 19801.

To this day, smallpox remains the only disease which humanity has completely eradicated. This is perhaps unsurprising given the framework of solidarity that was present in the world during that time. It is indeed remarkable what humanity can achieve when it works together.


References

1.         History of Smallpox | Smallpox | CDC. https://www.cdc.gov/smallpox/history/history.html (2021).

2.         Boylston, A. The origins of inoculation. J. R. Soc. Med. 105, 309–313 (2012).

3.         Hopkins, D. R. The Greatest Killer: Smallpox in History. (University of Chicago Press, 2002).

4.         McIntyre, J. W. & Houston, C. S. Smallpox and its control in Canada. CMAJ Can. Med. Assoc. J. J. Assoc. Medicale Can. 161, 1543–1547 (1999).

5.         History of Smallpox: Outbreaks and Vaccine Timeline. Mayo Clinic https://www.mayoclinic.org/coronavirus-covid-19/history-disease-outbreaks-vaccine-timeline/smallpox.

6.         Smallpox vaccine. Wikipedia (2023).

7.         Mark, C. & Rigau-Pérez, J. G. The world’s first immunization campaign: the Spanish Smallpox Vaccine Expedition, 1803-1813. Bull. Hist. Med. 83, 63–94 (2009).

8.         Parrino, J. & Graham, B. S. Smallpox vaccines: Past, present, and future. J. Allergy Clin. Immunol. 118, 1320–1326 (2006).

9.         Lyall, J. Leslie Collier. BMJ 342, d3084 (2011).

10.       History of smallpox vaccination. https://www.who.int/news-room/spotlight/history-of-vaccination/history-of-smallpox-vaccination.

11.        CDC Connects: Smallpox Eradication: Memories and Milestones, 10/26/2007.

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Boyan Tsankov

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