Monday, May 27, 2013

Scientific Exploits of Ben Franklin Part 2: Franklin Fights Smallpox

"Dr." Benjamin Franklin (1706-1790)
In our first blog post about Benjamin Franklin, I mentioned that Ben was, in many ways, ahead of his time.  Another good example of this was his recognition that scientific observation has an important place in medicine and his work to use science and statistics to improve medicine.  While he was called "Dr. Franklin," this title came from honorary doctorates given to him in 1759 by the University of St. Andrews in Scotland and 1762 by Oxford University in England.  These were in recognition of his contributions to physics and electricity.  Ben didn't have the university education that most of his contemporary scientists had.  He also had no formal training in medicine at all.  Nonetheless, beyond his contributions to theoretical science, he also designed medical equipment and devices, treated patients and made clinical observations, and helped to found The Pennsylvania Hospital in Philadelphia in 1752.  Ben also played an important role in the field of public health, most notably by acting as one of the major proponents for smallpox vaccination in the New World.      More after the jump....

Smallpox virus; CDC Public Heath Image Library #2292.

Smallpox was a disease caused by one of two viruses of the Poxviridae family, Variola major and Variola minor.  Infection with Variola minor usually causes only mild disease, while infection with Variola major is usually very severe.  An image of the virus particles is shown to the right, taken with a transmission electron microscope.  The viruses tiny, less than half of a micron across (1 micron is one millionth of a meter).  Even though they are too small to see with the naked eye, these viruses were among the most deadly killers humans have ever faced.  Smallpox was an exclusively human disease, as it is thought that there was no other natural host for the virus.  Smallpox is thought to have been around possibly as long as 12,000 years ago, and in the 20th century alone it is estimated that up to half of a billion people died of smallpox.  The overall mortality rate of the disease (the percentage of people who died from it) was about 30%.  Those who weren't killed by smallpox were often horribly disfigured by the terrible skin rash and blisters the disease causes (shown below).  Beyond the high fatality of ordinary smallpox in general, up to 5-10% of patients inexplicably developed horribly severe forms of the disease, known as malignant and hemorrhagic smallpox, that were almost always fatal.  

Smallpox blisters; CDC Public Health Image Library #2003
I keep writing that smallpox "was" a disease, because the last reported case of smallpox was in 1977.  Today, vaccination and other health policies have basically removed the smallpox  from the face of the earth.  The only known samples of smallpox virus exist in government labs that are (hopefully) tightly secured.  The elimination of this disease remains one of the great triumphs of modern medicine.  However, back in Ben Franklin's time, smallpox was a major public health problem.  At the time, smallpox was absolutely devastating.  Franklin undoubtedly watched countless people die from smallpox during his lifetime.

The disease first spread to the Americas from Europe in the 17th century.  In the American colonies of the late 1700s, smallpox was a common occurrence with a high mortality rate (15-30%).  It thus had an enormous impact on the American Revolutionary War.  The disease almost crippled the American army at points during the early war.  Rumors were rampant in the American colonies that the British were using smallpox as a means of biological warfare.  Coupled with the controversy among the colonists over smallpox inoculation (described below), the fear, illness, and death brought by smallpox had a major role in shaping the formation of the USA.       
Benjamin Franklin at his desk.
Hundreds of years before Ben Franklin and the American colonists lived, people in Europe and Asia recognized that if you survived a round of smallpox, you never got the disease a second time.  One infection seemed to confer life-long immunity.  This eventually lead to a practice called variolation, a form of inoculation.  You can think of variolation as an early form of vaccination with a live virus but without a standard vaccine formulation.  They would take a small amount of puss or dried scabs from the sores of a smallpox victim and put it into the nose or under the skin of someone who was uninfected.  This usually resulted in the uninfected person developing a milder case of smallpox than usually would occur if they had contracted it naturally, but it provided strong immunity against another infection.  This didn't always work, as occasionally the patient receiving the variolation inoculation would die from the resulting disease.  However, the scourge of smallpox was so devastating that there was a feeling among certain physicians in Franklin's time that inoculation was well worth the risk.  There was a lot of opposition, though.  Some people thought it was immoral to "infect" someone with a disease, even if it might save their life, while others thought the doctors were "playing god."  Most people, however, just did not understand the technique or have any idea of whether or not it was really beneficial.  As it would turn out, it would be Ben Franklin who was instrumental in convincing people that inoculation was indeed worth the risk.       

Franklin's Pennsylvania Hospital.  Engraving by Samuel Seymour, 1811.
While Ben's image is most closely tied to Philadelphia, Franklin was born in Boston in 1706 and lived there until he moved to Philly in 1723.  There was a major outbreak of smallpox in Boston in 1721, while Franklin still lived there.  Zabdiel Boylston, a Boston doctor who had heard about the use of inoculation in West Africa from a slave of the famous clergyman Cotton Mather, tried this strategy on his patients as well as himself and his own son.  When the epidemic subsided, Boylston and his son survived.  As Boylston began to count the deaths among Boston residents, he found that the mortality rate among those who received inoculations was only about 2.5% (6 deaths out of 244 people), much lower than the 15% rate of death among those who had not been inoculated and caught smallpox naturally (844 deaths out of 5980 people).  Franklin witnessed another outbreak of smallpox Boston in 1730, and he observed that out of a group of 72 people who had received prior inoculations, only two died, while the rest recovered to normal.  Ben noted that this was much lower than the 1 in 4 mortality rate in a group of individuals who contracted the disease naturally during that outbreak.  When yet another outbreak occurred in 1731, Ben saw only one death among a group of 50 inoculated people.  This phenomenon absolutely fascinated him, and he went to work compiling data and statistics on the benefits and risks of inoculation, aided in subsequent decades by physicians who worked at The Pennsylvania Hospital in Philadelphia.  

The cover of Heberden and Franklin's pamphlet.
Franklin knew from his data that inoculation worked, but he realized that he needed a famous medical authority to help him spread the idea of acceptance of inoculation to the Americas.  Franklin thus collaborated with a famous British physician, William Heberden (1710-1801), to write and publish a pamphlet describing the procedures, effects, and results of inoculation, titled Some Account of the Success of Inoculation for the Small-Pox in England and AmericaFranklin printed and distributed over a thousand of these pamphlets for free, many of which were used to encourage poor people of Philadelphia to inoculate their children.  Franklin realized that it was critical to have as many people as possible get inoculated, because even though inoculated people did not develop smallpox, they were still effective carriers that could spread smallpox.  However, Ben also recognized that many people could not afford the costs of inoculation, so in 1774, he helped to solicit money to establish a foundation called the "Society for Inoculating the Poor Gratis" which provided these services.  

Beyond the scientific, medical, and philanthropic bases of Ben's interest in inoculation lied a much more personal tragedy that sheds more light on why he fought for this cause with such fervor.  Franklin's youngest son, Francis Folger Franklin, also to his family as "Frankie," was born in 1732.  He was the light of Ben's life, and Ben wanted to get him inoculated against smallpox as soon as he was old and strong enough.  However, when Frankie was 4 years old, Ben wanted to inoculate him but held off because Frankie was recuperating from prolonged diarrhea, which was a much more serious problem in the 1700s than it is today in the US.  To Franklin's horror, while recovering from diarrhea, his son naturally contracted a case of smallpox that eventually killed him.  To add insult to injury, rumors spread rampant that a botched inoculation was responsible for little Frankie's death.  As a printer and publisher of Poor Richard's Almanac and The Pennsylvania Gazette, Franklin used his public outlets to write about and explain what actually happened to further push for the use of inoculations.  Even while writing his autobiography in 1788, Franklin included a reminder to his readers about how important it is that they immunize their children.  It was clear that the memory of his son still haunted him, as he wrote: 

In 1736, I lost one of my sons, a fine boy of four years old, by the smallpox, taken in the common way....I long regretted bitterly, and still regret that I had not given it to him by inoculation.  This I mention for the sake of parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it, my example showing that the regret may be the same either way and that, therefore, the safer should be chosen.  

The arguments against inoculation that irked Ben the most were the fervent religious objections.  Many religious leaders called the concept immoral because it interfered with "God's plan."  Others argued that deliberately infecting people with smallpox was in and of itself immoral as a violation of the sixth commandment of "thou shalt not kill," regardless of the potential to save lives.  While Ben's own religious beliefs are somewhat debated and unknown, he counteracted these arguments by presenting the idea that the real immorality lied in not using inoculation to save lives.  In 1750, he wrote that it is "impious to reject a method discovered by Mankind by God's good Providence, whereby 99 in 100 are saved."  Ben counteracted the religious objections by saying that the real moral imperative is to use the knowledge we have discovered for the greater good instead of ignoring it.  Based on this, one could argue that Ben Franklin was also America's first bio-ethicist.                      

George Washington (1732-1799)
The scourge of smallpox was so terrible that George Washington recognized its potential impact on the revolutionary war.  In 1777, then-general George Washington ordered compulsory inoculations for all new recruits who entered the Continental Army.  Washington himself contracted smallpox when he was 19; while he survived, he carried the scars for the rest of his life.  Faced with an army that was severely ravaged by smallpox, Washington knew he had to inoculate all of his troops, not just the new ones.  He believed it was absolutely necessary to win the war, as he could not fight without healthy troops.  Unknowingly, Washington was following the important concept of "herd immunity." Herd immunity is the concept that, within a group or a "herd," a larger percentage of individuals who are vaccinated against a contagious disease will result in a smaller likelihood that someone who is not vaccinated and susceptible will come into contact with someone who is infectious.  Washington's mass inoculation plan was carried out in secret, and then only with small groups of troops at a time.  Washington knew that the British would recognize that mass inoculation of the entire army would leave many soldiers somewhat ill, and even mildly ill soldiers are more vulnerable to attack than healthy ones.  Washington's plan likely saved the lives of many soldiers and was  a major reason why America was able to win its war for independence. 

Edward Jenner (1749-1823)
The inoculation technique of variolation remained the state-of-the-art way to control smallpox until the famous English physician and scientist Edward Jenner, often called the "Father of Immunology," discovered the the first form of modern vaccination in 1796, only a few years after Franklin died in 1790.  At the time, milkmaids would often contract an infection called cowpox, which results from a much milder virus that typically causes a rash only on the hands.  Jenner realized that the milkmaids who got cowpox never caught smallpox, even during smallpox outbreaks.  Jenner developed a smallpox vaccination using the cowpox virus, which was much safer.  The success and safety of Jenner's vaccine technique prompted then-president Thomas Jefferson to declare vaccination as the major public health priority of the still-young USA.  When Jefferson sent Lewis and Clark west to explore frontiers of the country in 1803, he made sure they had smallpox vaccinations both for themselves and included some to give to native American people they met.    

Thomas Jefferson (1743-1826)
Vaccines were the cornerstone of the policies that resulted in the World Health Organization declaring smallpox to be "eradicated" in 1979.  Some samples of smallpox virus still exist, most notably in the highly-secured storage facilities of the US Centers for Disease Control (CDC) in Atlanta and the Research Center of Virology and Biotechnology in Koltsovo, Russia.  However, the virus is mainly gone from nature.  The most recent small pox vaccinations use a different, even less virulent, vaccinia virus from the same family as variola (smallpox) and cowpox virus.  We now know that immunization with any virus from this family, which are all structurally similar to smallpox, causes the body to make antibodies that are effective against the entire family of viruses.  While adverse reactions can occur in up to 500 people out of every 1 million who receive the vaccine, only 1 or 2 people die for every million who receive the vaccines, making them extremely safe when compared with the disease itself.  However, the threat from smallpox is considered to be so low that most countries now only vaccinate people with a risk for occupational exposure, like laboratory workers or military personnel being sent to other countries.  However, public health organizations like the CDC are still vigilant.  Old smallpox samples still pop up from time-to-time, but it is unclear if the virus could survive for a hundred or more years on its own without being frozen.  In 2004, an envelope of smallpox scabs was found in an old book on Civil War medicine in New Mexico, and in 2011, the CDC confiscated small pox scabs that were on exhibit at a Virginia Historical Society display.  Neither of these had detectible levels of live virus, but it still remains a possibility that some small sample of the virus may be out there.   

Benjamin Franklin National Memorial, Philadelphia

Without the development of vaccines, smallpox would still be running rampant and killing people today.  As Howard Markel, a professor of History of Medicine at the University of Michigan, suggested in a 2011 New York Times essay, we should remember Ben Franklin and the history of smallpox the next time someone from an anti-vaccine lobby preaches that government-sponsored vaccines are outside of the US Founding Father's views for the country and its constitution.  One doesn't have to dig very deeply to see that three of the greatest Founding Fathers, Benjamin Franklin, George Washington, and Thomas Jefferson, understood how crucial vaccination is to protect the public health.  It is not coincidental that these men were also three of the most brilliant men of their time.  Their work pioneered the policies that allowed public health organizations to eradicate small pox and save  hundreds of millions of lives.   

Text © 2013 TheMadScienceBlog.  Images are public domain.

Sources and further reading:
  • J.V. Hirschmann.  "Benjamin Franklin and Medicine."  Annals of Internal Medicine.  2005. 143:830-834.   (subscription or pay-per-view only)
  • E.J. Huth.  "Benjamin Franklin's Place in the History of Medicine."  Journal of the Royal College of Physicians of Edinburgh.  2007.  37:373-378.
  • L. Gensel.  "The Medical World of Benjamin Franklin."  Journal of the Royal Society of Medicine.  2005.  98:534-538.  Available here.
  • A.M. Becker, "Smallpox in Washington's Army: Strategic Implications of the Disease during the American Revolutionary War."  The Journal of Military History.  2004.  68:381-430.  Available here.
  • H. Markel.  "Life, Liberty and the Pursuit of Vaccines."  The New York Times.  28 February 2011.  Available here.  
  • F. Fenner, D.A. Henderson, I. Arita, Z. Jezek, I.D. Ladnyi.  "Smallpox and its Eradication." World Health Organization.  Geneva.  1988.  Available here (link opens PDF). 
  • C. Flight.  "Smallpox: Eradicating the Scourge."  17 February 2011.  BBC History.  Available here
  • M. Best, A. Katamba, and D. Neuhauser.  "Making the right decision: Benjamin Franklin's Son Dies of Smallpox in 1736."  Quality & Safety in Healthcare.  2007.  16:478-480.
  • CDC Public Health Image Library 

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