http://www.raredr.com/contributor/jennifer-payne/10/2017/yellow-jacks
The Ghosts of Yellow Jack

Jennifer Payne

One of the most haunting unkowns that eluded early scientists for decades was the discovery of a viral agent for yellow fever, attributed with a 50% lethality rate that has remained much unchanged even today.1  

This month marks the 224th anniversary of America’s first major epidemic that took place in Philadelphia, PA. Widespread disease claimed the lives of 5000 out of a population of 45000, and forced another 17000 to flee the city.2 Victims who succumbed to the mysterious contagion were buried 10 to 15 bodies to a grave.3 Although an understanding of yellow fever has come a long way since the 18th century, the disease complexities continue to evolve and more work remains to be done. As of date, there is no approved drug therapy to treat persons afflicted with severe yellow fever disease, characterized by hemorrhagic fever, jaundice and multi-organ failure.4 And, despite advances in today’s modern technology, supportive care is often rendered ineffective.5 

While it has been known the primary mode of transmission is via an infected mosquito endemic to certain regions of Africa and South America, in more recent years exportation of the yellow fever virus by unimmunized travelers returning to their countries of non-endemic origin have been a contributing factor to increasing global burden of the disease. Outbreaks across 2015-2017 have occurred in Angola, the Democratic Republic of the Congo and Brazil.6 And, according to the CDC Morbidity and Mortality Weekly Reports, in 2015 alone “approximately 8 million US residents traveled to 42 countries with endemic yellow fever virus transmission7 thereby underscoring the need for prevention as critical to lowering disease risk and mortality.1

 Although one yellow fever (live) vaccine has been commercially licensed for use in the United States (YF-VAX, Sanofi Pasteur), the nation continues to be challenged by severe shortage  of the vaccine stock and the recent announcement confirming the imminent depletion due to issues in manufacturing. 

Currently, there are limited distribution centers for experimental vaccine (Stamaril, Sanofi Pasteur France) via an FDA approved expanded access pathway to help bridge the gap in demand until operations commence with a new YF-VAX vaccine manufacturing facility that is slated to open in 2018.6

Problems and Perceptions: Road to Immunogenicity

In general, the industry challenges surrounding distribution, manufacturing, large scale production, and resources (both financial and scientific knowledge) are not new; and they are not unique. However, when it comes to both drugs and biologics, what is uniquely American is the public attitude towards the preventative role therapies have in mitigating and combatting disease. This is a strikingly stark observation when it comes to vaccine and biotech development in particular, and manufacturers literally being forced to avert their biggest liability - failure - because of public perceptions. 

History has shown that correlates of protection through vaccination were often viewed as the new public enemy and even negated  the most noble scientific efforts of some of the earliest immunology advocates and 18th century variolation techniques – including Benjamin Franklin himself, who’s 4 year old son died of smallpox in 1736.8 Despite birth of the nation’s first public health agency in 1798 (and with proven results to follow in the fight against smallpox, cholera, and yellow fever),9 vaccination was still coined the “crime of the century” even 100 years later by medical establishment over efficacy and untoward side effects which are now better understood.10  

Twentieth century controversy evoked counter arguments and written avocations by a Dr. Richard Slee, one of the earliest founding fathers of Sanofi Pasteur (formerly known as Pocono Biological Laboratories) located in Swiftwater, Pennsylvania.  In a letter to Bergen County, New Jersey, Medical Society circa 1910, Slee eloquently foretold of prevention as the new public policy and driving force in delivery of today’s integrative health care in stating: “….We are now passing through the transition state, so to speak, and in a short time physicians will begin to realize that the regulations of the government are wise and that the failures from time to time are more than offset by the undeniable elimination of many severe and unpleasant sequelae.”10

Rising Fevers and Government Regulations
The transition state that Slee spoke peaked at the turn of the 20th century followed by a period of stagnant progress.11 For example, with the onset of the Spanish American War, it was reported for every 1 soldier who died in battle, 13 died of yellow fever,12 or “yellow jack” disease, often hallmarked by the yellow quarantine flag on ships.11 And, investigators commissioned under President Grover Cleveland to Cuba found early candidates for prevention ineffective because the isolation of the causative virus in rhesus monkeys was still another quarter of a century away.11 

Later advances in virus attenuation, tissue culture techniques and freeze drying finally gave way to mass production by the 1930s. But with the start of World War II and the distribution of 7 million doses of yellow fever vaccine across the years 1941-42 alone,11 more complications arose with serum stabilization induced hepatitis and an inordinate number of soldiers falling victim to the vaccine as opposed to the war.11 Fears of inadvertent inoculation of such spontaneous mutations and elimination of contaminants in yellow fever vaccine were laid to rest in the 1980s with genomic  research advances in the virus.11 Nevertheless, this new scientific era continues to underscore the need for quality control protection.  And, this has stood the test of time. 

Regulation of vaccine and antitoxin producers were first implemented with passage of the Biologics Control Act (BCA) of 1902. This bill was signed into law by President Theodore Roosevelt to assure the public of purity and potency standards and required both licensing and inspections of manufacturers following the St. Louis disaster (where an inordinate number of deaths in children resulted from tetanus-contaminated antitoxin).8, 9  The high standards set for purity and potency in early vaccine development history are as paramount today to playing a revolutionary role in transforming the biotech industry and have paved the way for Sanofi Pasteur as leading, world industrial giant in eradicating global disease. 

With US headquarters still based in Swiftwater, PA, Sanofi’s Pocono pride and heritage in cooperation, innovation, and education continues to help shape “a world in which no one suffers or dies from a vaccine preventable disease.”13 With the potential to vaccinate over 500 million people worldwide and much evidenced by a product portfolio of more than 1 billion doses of vaccine produced per year,14 it should be understandably noted  “approximately 70% of production time is dedicated to quality control.”15 The protective immune response  first conferred by identification of the 17D strain in yellow fever vaccine became further developed in the 1940s by the Rockefeller Institute and remains in use today.10 

Yellow fever technology was transferred to National Drug (purchaser of Slee laboratories in 1930) and has become one of Sanofi’s most remarkable achievements as the first ever freeze-dried vaccine in 1952.10 And, the legacy remains. As the sole manufacturer of YF-VAX in the US, Sanofi continues to make impact in the history of biologics with having saved countless lives through the contributions of its earliest founders and has left a spirit among Swiftwater that has lasted through the decades.

A Potpourri of the Paranormal

Dr. Richard Slee originally established the Pocono Biological Laboratories in 1896 for the proprietary production of glycerinated smallpox vaccine in Swiftwater and later formed a partnership with Dr. William Redwood Fisher to operate the laboratories across the years 1901-1908.10 Fisher made for an invaluable contact for Slee with providing the necessary capital for finding a competitive niche in both marketing and production, and to stay afloat the regulatory burden now posed to the growing industry of vaccine virus manufacturers with passage of BCA.10


 Dr. Fisher had settled in Swiftwater after leaving Hoboken for some respite care10 and built a house in 1901 literally across the street from Slee at the junction of Routes 611 and 314,10 which is now the subject of infamous haunts and monkey tales. Legend has it Fisher’s property was built upon a cemetery, and what was once buried has now been unearthed by new occupancy, (owner, Linda Schlier) and newly renamed, the Candle Shoppe of the Poconos.  Major activity at the Candle Shoppe is alleged to be attributable to primates subjected to experimentation by Fisher in his own brownstone basement biological laboratory while in the pursuit of cures on small pox and the disease that took his father’s life, yellow fever.10 Rising concerns among new tenants and Candle Shoppe workers has sparked a flurry of curiosity and intrigue, including Pennsylvania Paranormal Association investigators who have visited the property and given personal testimonials on unexplained touches, cold spots, moving shadows, shaking windows and EMF activity warranting follow up.  
In addition, owners’ reports of animal smells, monkey sounds, voices, falling candles and more  have set the stage for a special features presentation on Animal Planet’s, The Haunted; thereby making Candle Shoppe one of the Pocono’s most major visited paranormal attractions.  Guided history tours of the premises showcase a variety historical artifacts and medical paraphernalia. Treasured pieces among the collection include documents with Fisher’s name alongside partner Slee circa 1902, vaccines orders for US Army soldiers, photographs, and postcards. 

Also, monkey cages, holding cells, medical equipment and biological cabinets can be found; as well the opening of an underground tunnel to Sanofi which served as a primary means of distribution and transport of potentially biohazardous material from the laboratory in the 1900s.16

How much paranormal activity that can be substantiated or authenticated as proof for angry monkey spirits or even Fisher’s ghost may only be something left for the human experience and/or imagination. However, one thing is for certain. Fisher, holder of the purse and first treasurer of the Pocono Laboratories, also brought the expertise in medicine and management that Slee needed to expand in the wake of war, increasing demand of US military clients, and rising competition.10  

It was stated the partnership was founded originally for “promoting the art, trade, and business of manufacturing and selling vaccines, anti-toxins, chemicals and drugs, etc. in the village of Swiftwater.”10 But, following a period of dissolution of the partnering agreement in 1908, Slee reinvented himself without his partner in profit under the new name Slee Laboratories.10 In the midst of a vaccine revolution, Slee invoked the expertise of predecessors to modern day Lederle and Abbott Laboratories and relaunched in new partnership with his son in 1912.10 Although vaccines that were subsequently developed after Fisher’s death in 1926 are at the cornerstone of the Sanofi heritage, no apparent credit has been given to Fisher’s contributions or that can be found in documented literature. 

Because Slee’s name alone appears among Sanofi’s modern day tribute to early vaccine trailblazers,17 this begs the question on whether the vault of paranormal activity on Route 611 was really manifest from endeavors of an entrepreneurial spirit or a scorned spirit.

Regardless, the spirit of Sanofi does live on. And, the Monroe County myths and legends of Fisher’s vaccine vault will forever be told for generations to come. 

More on yellow fever vaccine and implementation of the eIND protocol for use of Stamaril in the United States can be found at the websites for CDC and Sanofi. 

http://www.sanofipasteur.us/vaccines/yellowfevervaccine
https://wwwnc.cdc.gov/travel/yellow-fever-vaccination-clinics/search

Happy haunts and safe travels!

References
  1. Staples JE, Gershman M, Fischer M. Department of Health and Human Services Centers for Disease Control and Prevention, Morbidity and Mortality weekly Reports, Yellow Fever Vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP), July 30, 2010/vol. 59/No. RR-7 www.cdc.gov/mmwr
  2. Harvard University Library Open Collections Program, Contagion, The Yellow Fever Epidemic in Philadelphia, 1793. http://ocp.hul.harvard.edu/contagion/yellowfever.html
  3. North RL. Benjamin Rush, MD: assassin or beloved healer? BUMC Proceedings 2000; 13:45-49
  4. 4 Department of Health and Human Services Centers for Disease Control and Prevention, Yellow Fever Vaccine Information Statement 3/30/2011
  5. Staples JE, Monath TP. (Commentary) Yellow Fever: 100 Years of Discovery, JAMA, August 2, 2008, Vol 300, No.8 (Reprinted) original JAMA article, JAMA 1901; 36(8):431-440
  6. Gershman MD, Angelo KM, JRitchey J et al. Department of Health and Human Services Centers for Disease Control and Prevention, Addressing a Yellow Fever Vaccine Shortage – United States, 2016-2017, MMWR/May 5, 2017/Vol. 66/No. 17 p457-459
  7. Gershman MD, Angelo KM, JRitchey J et al.. Department of Health and Human Services Centers for Disease Control and Prevention, Addressing a Yellow Fever Vaccine Shortage – United States, 2016-2017, MMWR/May 5, 2017/Vol. 66/No. 17 quoted in Data In, Intelligence Out [https://www.diio.net] unpublished data 2016
  8. McDonald S. Department of Health and Human Services US Food and Drug Administration, Science and the Regulation of Biological Products, September 2002
  9. Immunization Action Coalition (supported in part by National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC) in Atlanta, GA). Vaccine Timeline, http://www.immunize.org/timeline/
  10. Widmer J. The Spirit of Swiftwater 100 Years at the Pocono Labs, 1998 University of Scranton Press, US
  11. Frierson JG. The Yellow Fever Vaccine: A History, Yale Journal of Biology and Medicine 83 (2010), pp.77-78
  12. Staples JE, Monath TP. (Commentary) Yellow Fever: 100 Years of Discovery, JAMA, August 2, 2008, Vol 300, No.8 quoted in Bryan CS, Moss SW, Kahn RJ. Yellow fever in the Americas. Infect Dis Clin North Am. 2004; 18(2):275-292
  13.  http://www.sanofipasteur.us/about Copyright © 2017 Sanofi Pasteur SA. last updated on 24-Oct-2017
  14.  http://www.sanofipasteur.us/about/facts Copyright © 2017 Sanofi Pasteur SA. last updated on 24-Oct-2017
  15.  http://www.sanofipasteur.us/essentials/development Copyright © 2017 Sanofi Pasteur SA. last updated on 24-Oct-2017
  16.  Author, Guided Tour, The Candle Shoppe of the Poconos, 1900 Rt. 611 Swiftwater, PA  18370 February 2017, last visited October 2017
  17. http://www.sanofipasteur.us/about/heritage Copyright © 2017 Sanofi Pasteur SA. last updated on 24-Oct-2017

Photo by the author, Yellow Vaccine Allotment Bins of Dr. William Redwood Fisher, Biological Research Laboratory circa 1900s, basement of The Candle Shoppe of the Poconos, October 2017
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