Major Epidemics in the

History of Medicine

Center for History Of Medicine and

Archives and Rare Books

Winter 2016

January 6 – February 3

M04 579H

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 1 of 23

Major Epidemics in the History of Medicine – M04 579H

Syllabus

Description/Objectives:

Points to be emphasized include the world-wide effects of such epidemics (bubonic plague), the discovery of vaccination and the ability to completely eradicate a major disease (small pox), the importance of insect-vector diseases, such as malaria and yellow fever, as well as the emergence into the developed world of new insect-carried disease such as dengue fever, Zika virus disease, and chikungunya, venereal disease and epidemics of modern times such as influenza and AIDS. Most of the diseases to be discussed are still prevalent, and patients suffering from these diseases will be seen and treated by the medical students during their medical career. At the end of this course, students will be able to:

• Identify some of the most important and devastating epidemics in the history of medicine, beginning in antiquity and continuing into the 21st century;

• Describe the clinical and pathological findings of each disease, and how medical science responded to the threat of each epidemic;

• Understand how immunization and treatments to reduce the spread of epidemics were developed by medical science; and

• Understand that the threat of epidemic disease still occurs in spite of past advances in medicine and public health.

Locations: Center for History Of Medicine, Bernard Becker Medical Library, 6th floor; Archives and Rare Books, Bernard Becker Medical Library, 7th floor

Time: Wednesday, 3:30 – 5:30 p.m. (unless otherwise noted) Format: 3:30 – 5:00 p.m. Students discuss and summarize assigned articles – Center for History Of Medicine; 5:00 – 5:30 p.m. Examination of Archival Materials --- Archives and Rare Books

Subjects to be discussed:

Week I – The Black Death: Bubonic Plague

Week II – Smallpox and Vaccination

Week III – Insect-Carried Diseases: Malaria and Yellow Fever

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 2 of 23

Week IV – Tuberculosis and Syphilis

Week V – Modern Epidemics: Influenza and AIDS

Participants:

WUSM I Students

Becker Library Archives and Rare Books Staff Ms. Elisabeth Brander, Rare Book Librarian

Mr. Stephen Logsdon, Archivist Ms. Martha Riley, Rare Books Cataloger & Archivist Mr. Philip Skroska, Visual and Graphic Archivist

Faculty

Robert M. Feibel, MD, Professor of Clinical Ophthalmology and Acting Director of the Center for History Of Medicine Ernie-Paul Barrette, Associate Professor of Medicine, Division of Infectious Diseases

Contact: Ms. Debra Knox Deiermann, 314/362-2725; CfHOM@wusm.wustl.edu

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 3 of 23

Major Epidemics in the History of Medicine – M04 579H Readings

Week I – The Black Death: Bubonic Plague

Required reading Sherman IW: Power of Plagues, Chapter 4: “An Ancient Plague, the Black Death”

Recommended reading Cohen J, Powderly, WG: Infectious Diseases, 2nd Edition Gage KL: Chapter 120: “Plague”

https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323045797001209 Individual assignments 1. Berche P: Louis Pasteur, From Crystals of Life to Vaccination http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2012.03945.x/epdf 2. Blevins SM: Robert Koch and the ‘Golden Age’ of Bacteriology http://www.sciencedirect.com/science/article/pii/S1201971210023143 3. Zietz BP: The History of the Plague and the Research on the Causative Agent Yersinia pestis http://www.sciencedirect.com/science/article/pii/S1438463904702771 4. Butler T: Plague History: Yersin’s Discovery of the Causative Bacterium in 1894 Enabled, in the Subsequent Century, Scientific Progress in Understanding the Disease and the Development of Treatments and Vaccines http://onlinelibrary.wiley.com/doi/10.1111/1469-0691.12540/epdf 5a. CDC Morbidity and Mortality Weekly Report: Human Plague – United States, 2015 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6433a6.htm 5b. Kugeler KJ: Epidemiology of Human Plague in the United States, 1900-2012 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4285253/pdf/14-0564.pdf 6. Barras V, Greub G: History of Biological Warfare and Bioterrorism http://onlinelibrary.wiley.com/doi/10.1111/1469-0691.12706/epdf

Week II – Smallpox and Vaccination

Required reading Sherman IW: Power of Plagues, Chapter 9: “Smallpox, the Spotted Plague”

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 4 of 23

Recommended reading Cohen J, Powderly, WG: Infectious Diseases, 2nd Edition: Practice Point: d) Initial Management of a Suspected Outbreak of Smallpox

Individual assignments 1. Eyler JM: Smallpox in History: The Birth, Death and Impact of a Dread Disease

http://www.sciencedirect.com/science/article/pii/S0022214303001021

2. Rutkow IM: Zabdiel Boylston and Smallpox Inoculation http://archsurg.jamanetwork.com/article.aspx?articleid=392281

3a. Smith GF: Edward Jenner and the Small Pox Vaccine http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342363/pdf/fimmu-02-00021.pdf

3b. Brunham RC: In Celebration of the 200th Anniversary of Edward Jenner’s Inquiry into the Causes and Effects of the variolae vaccinae

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342363/pdf/fimmu-02-00021.pdf

4. Semba RD: The Ocular Complications of Smallpox and Smallpox Immunization

http://archopht.jamanetwork.com/article.aspx?articleid=415346

5a. Albert, MR: The Last Smallpox Epidemic in Boston and the Vaccination Controversy, 1901-1903 http://www.nejm.org/doi/pdf/10.1056/NEJM200102013440511 5b. Parmet WE: Individual Rights versus the Public’s Health – 100 Years after Jacobson v. Massachussetts http://www.nejm.org/doi/pdf/10.1056/NEJMp048209 6. Stern AM: The History of Vaccines and Immunization: Familiar Patterns, New Challenges http://content.healthaffairs.org/content/24/3/611.full.pdf 7. Clemmons NS: Measles – United States, January 4 - April 2, 2015

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6414a1.htm 8. Jacobson RM: Vaccine Hesitancy http://www.sciencedirect.com/science/article/pii/S0025619615007193

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 5 of 23

Week III – Insect-Carried Diseases: Malaria and Yellow Fever

Required reading Sherman IW: Power of Plagues, Chapter 7: “Malaria, Another Fever Plague” Sherman IW: Twelve Diseases that Changed Our World, Chapter 9: “Yellow Fever: the Saffron Scourge”

Recommended reading Cohen J, Powderly, WG: Infectious Diseases, 2nd Edition, Chapter 111: “Malaria” https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323045797001118 Cohen J, Powderly, WG: Infectious Diseases, 2nd Edition, Chapter 164: Zoonotic Viruses

https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323045797001118 Individual assignments

MALARIA 1) Cox FEG: History of the Discovery of the Malaria Parasites and their Vectors

http://download.springer.com/static/pdf/984/art%253A10.1186%252F1756-3305-3-5.pdf?originUrl=http%3A%2F%2Fparasitesandvectors.biomedcentral.com%2Farticle%2F10.1186%2F1756-3305-3-5&token2=exp=1467135022~acl=%2Fstatic%2Fpdf%2F984%2Fart%25253A10.1186%25252F1756-3305-3-5.pdf*~hmac=027892b11357da085e334fb8f2107ab76ac006dc7e9a4baed7557094479033e4

2) Benedek T: History of Malaria Chemotherapy http://www.antimicrobe.org/h04c.files/history/malaria.pdf

3) Capanna E: Grassi versus Ross: Who Solved the Riddle of Malaria? http://scielo.isciii.es/scielo.php?pid=S1139-67092006000100010&script=sci_arttext

4) Miller LH: Artemisinin: Discovery from the Chinese Herbal Garden http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414217/

YELLOW FEVER 1) Patterson KD: Yellow Fever Epidemics and Mortality in the United States,

1693-1905 http://www.sciencedirect.com/science/article/pii/027795369290255O

2) Bean WB: Walter Reed and Yellow Fever [Awaiting link]

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 6 of 23

3) Frierson JG: The Yellow Fever Vaccine: A History

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892770/pdf/yjbm_83_2_77.pdf

4) Dick OB: Review: The History of Dengue Outbreaks in the Americas http://www.ajtmh.org/content/87/4/584.full.pdf+html

5) Peper SM: That Which Bends Up: A Case Report and Literature Review of Chikungunya Virus http://link.springer.com/article/10.1007/s11606-015-3459-3/fulltext.html

Week IV – Tuberculosis and Syphilis

Required reading Sherman IW: Power of Plagues, Chapter 12: “The Great Pox, Syphilis” Sherman IW: Twelve Diseases that Changed Our World, Chapter 7: “Tuberculosis: the People’s Plague”

Recommended reading Cohen J, Powderly, WG: Infectious Diseases, 2nd Edition, Chapter 30: “Tuberculosis and Other Mycobaterial Infections” https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323045797000307 Cohen J, Powderly, WG: Infectious Diseases, 2nd Edition, Chapter 57: “Syphilis”

https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323045797000575

Individual assignments SYPHILIS 1) Frith J: Syphilis – Its Early History and Treatment Until Penicillin, and the

Debate on its Origins http://jmvh.org/wp-content/uploads/2013/03/Frith.pdf

2) O’Shea JG: ‘Two Minutes with Venus, Two Years with Mercury’ – Mercury as an Antisyphilitic Chemotherapeutic Agent http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292694/pdf/jrsocmed00135-0062.pdf

3) Thorburn AL : Paul Ehrlich: Pioneer of Chemotherapy and Cure by Arsenic (1854-1915) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1046247/pdf/brjvendis00012-0056.pdf

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 7 of 23

4) Bialynicki-Birula R: The 100th Anniversary of Wasserman-Neisser-Bruck Reaction http://www.sciencedirect.com/science/article/pii/S0738081X07002040

TUBERCULOSIS 1) Daniel TM: The History of Tuberculosis

http://www.sciencedirect.com/science/article/pii/S095461110600401X

2) Sakula A: Robert Koch: Centenary of the Discovery of the Tubercle Bacillus, 1882 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC459292/pdf/thorax00196-0006.pdf

3) Daniel: Captain of Death, Chapter 21: “Sanatoria” (on reserve in library)

4) Daniel: Captain of Death, Chapter 13: “Tuberculin” (on reserve in library)

5) Daniel: Captain of Death, Chapter 15: “BCG vaccine” (on reserve in library)

6) Kingston W: Streptomycin, Schalz v. Waksman, and the Balance of Credit for Discovery http://jhmas.oxfordjournals.org/content/59/3/441.full.pdf+html

Week V – Modern Epidemics: Influenza and AIDS

Required reading Sherman IW: Twelve Diseases that Changed Our World, Chapter 10: “The Great Influenza” Sherman IW: Power of Plagues, Chapter 5: “A Modern Plague, AIDS”

Recommended reading Cohen J, Powderly, WG: Infectious Diseases, 2nd Edition, Chapter 161: “Influenza viruses” https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323045797001611 Individual assignments 1) Ghendon Y: Introduction to Pandemic Influenza Through History

https://flutrackers.com/forum/forum/welcome-to-the-scientific-library/pandemics-in-literature/22979-introduction-to-pandemic-influenza-through-history

2) Kilbourne ED: Influenza Pandemics of the 20th Century http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291411/pdf/05-1254.pdf

3) Taubenberger JK, Morens DM: Influenza: The Once and Future Pandemic

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 8 of 23

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862331/pdf/phr125s30016.pdf

4) Bristow NK: It’s as Bad as Anything Can Be: Patients, Identity, and the Influenza Pandemic http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862342/pdf/phr125s30134.pdf

5) Sencer DJ, Millar JD: Reflections on the 1976 Swine Flu Vaccination Program http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291400/pdf/05-1007.pdf

Cohen J, Powderly, WG: Infectious Diseases, 2nd Edition, Chapter 84: Epidemiology of HIV infection https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323045797000848 Individual assignments 1) A Timeline of AIDS

https://www.aids.gov/hiv-aids-basics/hiv-aids-101/aids-timeline/

2) Gallo RC, Montagnier L: The Discovery of HIV as the Cause of AIDS http://www.nejm.org/doi/full/10.1056/NEJMp038194

3) Gallo RC, Montagnier L: Propects for the Future http://science.sciencemag.org/content/sci/298/5599/1730.full.pdf

4) Cohen J, Enserink M: HIV, HPV Researchers Honored, But One is Left Out http://science.sciencemag.org/content/sci/322/5899/174.full.pdf

5) Markel H: When Germs Travel (pp. 149-153; 159-176)

6) Mustich E: A history of AIDS hysteria http://www.salon.com/2011/06/05/aids_hysteria/

7) Altman LK: 30 Years In, We Are Still Learning From AIDS http://www.nytimes.com/2011/05/31/health/31aids.html?_r=3&ref=lawrencekaltman

8) Maxmen A: Ebola Panic Looks Familiar to AIDS Activists http://www.newsweek.com/2014/11/14/ebola-panic-looks-familiar-aids-activists-281545.html

9) Smith RA: Drugs into Bodies! A History of AIDS Treatment Activism http://www.thebody.com/content/art31153.html

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 9 of 23

10) Epstein S: The Construction of Lay Expertise: AIDS Activism and the Forging of Credibility in the Reform of Clinical Trials (pp. 413-417; 427-430) http://www.jstor.org/stable/689868?seq=1#page_scan_tab_contents

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 10 of 23

Major Epidemics in the History of Medicine – M04 579H

Student Summaries

This class has given me a general overview of the effects of infectious diseases on human history. Human civilization has had to contend with microbial pathogens since its foundation. Many human institutions were shaped, or at least influenced, by infections, such as urban planning and sanitation. Even before it was known what caused infectious diseases, it was known that they were contagious. As a result, people tried to isolate the sick or place them under quarantine to prevent the spread of infection, representing the oldest medical practice that is still in use today. The discovery of its cause and development of effective treatments revolutionized the field of medicine with germ theory and sterile technique, allowing it to take its modern form. Medicine became evidence-based, practiced by scientists instead of clergyman or traditional healers.

No other form of disease has changed the course of history as much as infectious disease. Epidemics caused by new pathogens infecting naïve hosts have caused, or at least contributed to, the collapse of civilizations, especially those of the Americas. There is little doubt that Europeans would have had the same success in colonizing the Americas if they had not introduced many new pathogens for which the native population had little existing immunity. The effects of infectious diseases can be less dramatic, not causing the collapse of civilization but instead changing the outcome of a war, such as the Athenian Plague did with the Peloponnesian War, or changing the fundamental structure of society, as the Black Death did in the late Middle Ages to promote the beginning of the Renaissance. Infectious diseases have continued to exert their influence in the modern era, as with the Spanish Flu that contributed to the Central Powers’ defeat in World War I.

Having effective means of treating and preventing infections has fundamentally changed the human experience. Vaccines and antibiotics have drastically decreased infant and child mortality in the developed world and extended life expectancy to its present extent. They have also led to an epidemiological shift, in which most of the morbidity of the population is associated with non-infectious chronic diseases. As a result, infectious disease receives less money and attention from academia, industry, and the government. The prevailing viewpoint is that pathogens are under control and no longer pose a threat to humanity, but this is far from the truth. Pathogens still ravage parts of the third world, including some for which there are effective treatments or vaccines. New pathogens continue to emerge and spread faster than ever before due to modern transportation. Finally, long-established pathogens that have been largely controlled in the developed

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 11 of 23

world are threatening to return due to drug resistance and anti-vaccination movements. This course has re-affirmed my commitment to microbiology and infectious disease, and I hope to address these issues in my career.

Thoughts on Major Epidemics

We learned a lot in our course on Major Epidemics: not just the medical and epidemiological aspects of diseases that have caused epidemics, but also the social and economic impact that the diseases had at the time. However, the biggest takeaway I had from the course is the potential for a future disease to cause a similar epidemic. It seems to me that the world is a ripe for another major epidemic.

Throughout this course we learned that epidemics often occurred when there was a high population density combined with a lack of cleanly conditions. Human population continues to grow at an exponential pace, and it seems almost self-evident that our world’s cities will be unable to provide enough resources to take care of the ever-increasing population. The lack of resources will lead to unclean conditions and people living in close proximity, both of which will lead to a fertile breeding ground for an infectious organism.

The organism that will be the culprit of the next major epidemic is less clear. I think a strong case could be made for both a virus and a bacterium. A virus is especially dangerous because there does not exist an effective treatment for many viruses. For example, there still does not exist an effective treatment for yellow fever, so an outbreak of the disease could be very deadly yet again. However, I think a scarier scenario would be if one of the current viruses mutated to become significantly more deadly. What if the Ebola virus acquired an ability to transmit by airborne transmission? What if the influenza virus mutated in such a way to become much more deadly? Both scenarios could do far more than decimate humanity.

Another very scary scenario would be if a deadly, contagious bacterium acquired resistance to all known and effective antibiotics. For example, what if one of the common culprit organisms of bacterial meningitis suddenly becomes resistant to all known antibiotics. What if Mycobacterium Tuberculosis acquires such resistance? There are already case reports of total-drug resistance M. Tuberculosis bacterium. What if the causative agent of the black plague, Y. Pestis, were to acquire full resistance? Another plague outbreak could be inevitable if sufficient resources were not dedicated to cleaning our cities.

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 12 of 23

Perhaps the scariest scenario is not the natural evolution of a lethal organism, but instead of a deadly organism designed to kill humanity. It seems very easy to imagine designing an organism in a lab with a variety of lethal virulence factors. If a terrorist were to attempt this, I think it would be very easy to kill most of the world’s population.

The Bubonic Plague

Looking back into the depths of the history of medicine, a few illnesses/epidemics stand out as having truly changed the course of human history. One of these major epidemics was the bubonic plague, which killed more than 200 million people in the course of 3 pandemics and threatened the very existence of human beings. Despite leaving a devastating number of deaths in its wake, however, the plague also brought about some major socioeconomic changes that positively changed the path of humanity. At the same time, and quite unfortunately, it also brought out some vile human characteristics and was used as a medium to propagate hatred towards certain population groups.

When studying the major epidemics in human history, one recurring theme that’s seen is the concept of a blame culture. It is in our very human nature to want to have something/someone to blame for unfortunate incidences. Prior to the advent of the germ theory, without much knowledge of the causes of illnesses, the blame mostly targeted certain population groups. Often these population groups were stigmatized against even before the onset of the epidemics. The epidemics merely provided a reason for populations to blame their enemies. In the case of the Black Death, the unlucky targets of this inevitable blame were the Jews. The anti-Semitism practices that had begun a couple centuries prior continued to spread with full force. The people of Jewish origin were blamed to have caused the plague and were persecuted, denied land ownership, and even burned to death.

On a more positive note, however, the bubonic plague did bring about some great strides in the fields of medicine and education. During the time, academic physicians relied on the teachings of Galen that stated that diseases were a result of an imbalance in the 4 humors of the body. The plague, however, did not have much to do humoral changes and therefore confidence in Galenian system slowly declined. Eventually, studies of human anatomy in the context of health/disease began to be emphasized and the practice of medicine was altered forever. In terms of education, the various quarantines and restrictions on travel prevented people from enrolling at the few available distant universities. Fortunately, this turned out to be a positive thing because it led to the establishment of new universities all over Europe and even brought about curricular reform.

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 13 of 23

The mark that the bubonic plague left in human history is unlike any other. In addition to the significant number of lives it claimed, it has altered various aspects of the socioeconomic fabric of the societies it, quite literally, plagued. One can only imagine how different the world we currently live in would be, had its history not been significantly altered by the bubonic plague.

Reference

Sherman, Irwin W. The Power of Plagues. Washington, D.C.: ASM, 2006.

Beyond Death: The Plague and the Entry of Europe into the Early Modern Era

Until the time the Black Death struck Europe in the early part of the second millennium AD, Europe was entrapped in what was known as the Dark Ages – an era of stilted social mobility, strict rules from the governing bodies such as the Catholic Church and the various monarchies across the lands, and a rather stifled approach to art, science, literature, and philosophy. Few works, if any, from the Dark Ages have gained much repute in the current era. Yet, with the entrance of Yersinia pestis from the East, Europe was thrown into chaos. With the large percentage of population dying, and the lack of viable treatments and means by which to deal with this crisis, Western civilization was on the brink of collapse. But rather than collapsing, the Black Death allowed a transition into a new era, an era of revival, of Enlightenment, a Renaissance of sorts.

It is historical fact that the Renaissance could not have happened without the conditions introduced by the plague. In response to the rampant death and dreariness caused by the disease, the hold of the Church on the population began to slip, as there was no religious explanation or salvation from the Black Death. Astrology emerged as a viable scientific option. The persecution of the Jews, as has happened periodically in history during times of strife, reemerged. Monarchs introducing strict laws became overwhelmed by pirates, resulting in the cessation of the 100 Years War, if just for a few decades. Along with the death came the alleviation of the European overpopulation issue, resulting in increased social mobility for peasants and a shattering of the feudal system. The death of nobility weakened the ruling class, allowing for a new middle class to emerge. Land was easily purchased, wages increased, and serfdom disappeared, especially in Western Europe. More economic experts allowed for the enrichening of the middle class.

An impact equally as important and revolutionary was seen in literature, science, and art. As stated above, the Dark Ages that preceded the Black Death had a dearth of advances in literature and art. However, due to the plague, there was an explosion of

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 14 of 23

classic literature, including such seminal works such as The Canterbury Tales by Geoffrey Chaucer, The Decameron by Boccaccio, the collected works of Petrarch, and even influencing Dante’s Divine Comedy. The ramifications for the scientific world were equally as massive, as legend states that Newton came up with the ideas of calculus and gravity whilst Cambridge was closed during a later iteration of the Black Death. The greatest impact could be seen on the art world, however. The plague essentially removed the linearity and religious focus of art in the Dark Ages period. This new focus allowed for the artistic revolution, culminating in the works of Da Vinci, Raphael, Donatello, and Michelangelo. In short, those considered to be the pinnacle of the modern world, and even the social structure of Western Civilization would not have been possible without the tragedy of the Black Death.

Major Epidemics in the History of Medicine Response Paper

When people speak of the advances of modern medicine, it often evokes images of radical new cancer therapies, transplant surgeries or incredible new imaging technologies. However, for all the advances in other fields of medicine, the most dramatic improvement in overall quality of life and life expectancy in the developed world during the past 150 years came from an improved understanding of our microbial invaders and cohabitants. The eradication of smallpox stands as a crowning achievement, but the drastic decrease in mortality from epidemics such as tuberculosis, malaria, syphilis, and even recently AIDS displays the breadth of improvement over the past century. However, despite these many improvements, the microbial world has displayed a remarkable ability to adapt and will continue to challenge all parts of the modern world.

The most striking part of the course for me was the incredible impact that these epidemics have had on the course of history. In many ways, the annals of history are filled with the stories of major leaders, battles, and events that changed the course of the world. However, these tiny microbes, from the Plague that ravaged Europe and laid the groundwork for the Renaissance to the insect-borne Yellow Fever that may have halted Napoleon’s interest in the Americas. Furthermore, the most intriguing fact for me was the influence of the Spanish Influenza on Woodrow Wilson during the Treaty of Versailles negotiations following the end of World War I. Had Wilson not been very ill during the negotiations, it is possible that the punishments for Germany may have been much lighter, possibly not enough to set the stage for World War II that followed and radically changed our world. In the distant future, when the history of our current time is written, it is very likely that microbial pathogens will continue to play a pivotal, albeit underappreciated,

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 15 of 23

role.

Major Epidemics in the History of Medicine Final Summary

Few things have shaped the world that we now know today more than infectious disease, and its resulting effects on population, policy, and more. The epidemics that we discussed in class—the bubonic plague, smallpox, malaria, yellow fever, tuberculosis, syphilis, influenza and HIV/AIDS—were incredibly significant occurrences in history, but only represent some of the diseases that have ravaged populations all over the world, and, in some cases, continue to do so.

I think what struck me most about what we discussed over the last five sessions is how much these diseases continue to affect the world today. Unvaccinated children are contracting measles, which is easily preventable and thought by many Americans to be basically impossible to catch, at Disneyland. Diseases such as yellow fever and malaria are barely on anyone’s radar in the U.S., but in Africa or South America, these are illnesses that affect people’s day to day lives, leading to 30,000 and 438,000 deaths, respectively. As someone who has traveled to several countries where these illnesses are rampant, I was fortunate enough to be able to procure a yellow fever vaccine and malaria pills to protect myself prophylactically. In contrast, residents of these countries, who may not have the resources to access these same medications, suffer from diseases that could be easily evaded with simple medications.

Furthermore, the issue of drug resistance has become steadily worse, forcing scientists all over the world to scramble for new solutions. This has been evidenced very clearly in malaria, which saw the transition from the quinine in cinchona bark, to synthetic medications, from quinolone to quinacrine to the newer, Nobel-Prize worthy discovery of Artemisinin. Similarly, HIV, a disease that does not carry the same stigma as it used to but still affects 50,000 new people a year, can be controlled, but not treated, by anti-retroviral drugs. When patients adhere to their medications, their illness can be controlled, and their CD-4 T-cell numbers can be kept at acceptable levels. However, when patients begin to become non-adherent to their HAART, this is when drug resistance can develop. Suddenly, their disease becomes very difficult to control, and can progress to full-blown AIDS, leading to severe opportunistic infections, and death.

However, there is some promise. One disease, smallpox, was declared in 1980 to have been successfully eradicated by vaccination, invented by Edward Jenner. Though other diseases still exist sporadically throughout the world, many solutions have been

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 16 of 23

invented already to control and contain them. Hopefully, through the further advances of scientific innovation and research, and smart practices such as vaccination and disease reservoir control (such as mosquito breeding), we will be able to experience the eradication of more infectious illnesses in our lifetime.

In conclusion of the course, I find myself both in awe and fear of the scale and calamity of past epidemics, and the potential for a future epidemic to devastate the human population. The capacity for a pathogen to wipe out 5% of humanity sounds absurd, and yet it has happened in the past, and may happen again in the future. Perhaps what is most frightening is that some of these pathogens still do not have a cure.

Yet in the context of this course, I have also learned how humanity has combatted these epidemics to prevent endangerment and extinction. From the early thoughts of Louis Pasteur hypothesizing the etiology of infections as pathogenic organisms to the advances sequencing we can do now to identify the origin of viral outbreaks, the methodology of combatting epidemics have been a testament to scientific progress and thinking. As a 1st year MSTP interested in doing research for the rest of my career, I appreciate some of the techniques used to understand different pathogens. For example, by filtering serum and re-inoculating animals, scientists could determine whether a pathogen was of viral or bacterial origin. Another example that I thought as a triumph in modern diagnostics was the Wasserman-Neisser-Bruck serological test. Its development relied on collaboration from numerous scientists, some from different fields, to make a cohesive picture of complementation and pathogenesis. The result was a paradigm that could be broadly applied to other pathogens.

The HIV epidemic was a phenomenal case study of how scientific progress, when pooled in a collaborative fashion, could drastically combat an epidemic at a population level. The parallel use of education, research, and deployment allowed HIV infections to drop dramatically over the span of two decades. Given that the average development time for a new pharmacological therapy is ~ 10 years, the dozens of medicines now available to consumers is astonishing.

On the flip side, our inability to cure influenza is a testament to how much we have still yet to learn about pathogenesis. While we are constantly advancing our understanding of pathogens, pathogens are constantly evolving, in part because of our increased selection pressures to combat them. In somewhat of a cyclic process, pathogens are developing ways to avoid our treatments, which will always make epidemics a threat. Because of this, we have and must continue to rely on education, prevention (in the form of vaccinations), and

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 17 of 23

social practices to block off transmission pathways and prevent an uncontainable spread should an infection occur. There is much to learn from our forefathers in dealing with epidemics, and also much to discover.

Reflections on Vaccination

There is no doubt that the advent of vaccination has had tremendous impact on the burden of infectious disease, allowing humankind to spare future generations the fear, suffering, and body count of plagues of the past, some now relegated to vestigial pockets of the Earth or even eradicated completely. In Major Epidemics, our coverage of vaccines from their roots in variolation through modern-day challenges provided not only historical perspective, but also an awareness of the challenges that persist today and context for their existence in society. In particular, I feel that our approach to this issue is of value to all medical students, not only those who take the selective. Throughout the first year of medical school thus far, a major focus in our Principles of Medicine course has been the development of communication skills appropriate for providing competent, ethical patient care, and of course an understanding of health literacy. What I have not yet seen is a consideration of patients’ attitudes toward specific issues of interest in medicine.

The reading on vaccine hesitancy from Jacobson, St. Sauver, and Finney Rutten is illustrative of the many attitudes patients and parents may bring to the care “table.” The issues discussed include factors that professionals educated in the sciences might be unlikely to include in their own thinking or recognize in others. In particular, familiarity with interpretation of scientific data and “the nature of scientific evidence,” as the authors put it, represents a significant advantage in the ability of a physician, as compared to a lay person, to form and justify opinions using research data. This sort of fundamental difference in the way the numbers and figures are interpreted or integrated into one’s existing set of knowledge and opinions is something I had not explicitly recognized before. Somewhat ironically, the authors forget this very factor in their C.A.S.E. approach example, offering scientific data to the hypothetical patient without explicit interpretation, inviting him to draw his own conclusions (whatever those may be) and demonstrating quite powerfully the creeping bias that accompanies scientific literacy.

When antivaccination sentiment was first born, the nature of communication was different. The internet provides a means for propagation of opinion, not only spreading antivaccination sentiment disguised as whistleblowing, but also allowing the lay public to develop scientific “literacy” independent of formal education. This is a double edged sword, as the internet is brimming with lay evaluations of scientific data, often poor and

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 18 of 23

sometimes malicious replacements for legitimate critical inquiry. While physicians continue to be formally educated and scientifically literate as a result, the public is in many ways undergoing a dramatic shift in information access. I think exposure to ideas like these early on has been a significant benefit of attending the Major Epidemics course, and I think this is the sort of thing we should be adopting for all medical students. The better we understand the nature of the differences between our perspectives and those of our patients, the better we can address the constantly changing external factors that are at play in providing care.

I am very interested in infectious diseases and have read several papers on various bacteria, parasites and viruses for classes and for my research. These have all been technical papers. This class was quite unique. I had never considered the history of major infectious epidemics as an important component of our current understanding of infectious diseases, both in basic science research and preventions/treatments. I learned a lot in this class. For example, vaccines are now currently produced by big pharma for profit while they were funded by governments during the very early stages of vaccinations. Today, very few pharmaceutical companies produce vaccines because of the regulatory and economic burden. The regulatory process is necessary though to provide safe vaccines for the population. We do not want a repeat of the Lubeck tragedy where scientists mislabeled live TB as the attenuated version!

It is quite fascinating to read about some simple, yet elegant experiments that doctors and scientists performed to determine critical information on various pathogens. The discovery that the plague bacteria were passed from rat to rat by fleas was through a great experiment with extremely good controls and set the precedent for several techniques used today.

The history of infectious diseases have also influenced the physician-patient relationship of our time. There are several minority groups whose trust in doctors is disturbingly fragile. After all, Haitian women detained in Guantanamo in the early 90’s were injected with contraceptives without consent. The trust between such groups and American doctors will take several decades to rebuild. As a future doctor it is imperative to understand the history of medical discrimination and experimentation on minorities and factor this into discussions with future patients.

While several antidotes for epidemics seem comical now, we should not forget people had faith in them. The general population always has “blind faith” in doctors and scientists to discover and deliver quality cures for their diseases, even today. To me, this

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 19 of 23

implies meticulous analysis of experimental setups and data, processes that Robert Koch and Louis Pasteur followed religiously. Through this class I have been enlightened on some of the history of the field of infectious diseases and the challenges it has overcome. I hope to contribute to this history as a physician and a scientist in the future.

Major Epidemics Final Paper

In tracing through history’s greatest epidemics, we have come to appreciate the commonalities between them and the possibility of using this knowledge for inevitable future adversaries. For instance, history has shown that major changes in the living conditions of humans and the structure of society has previously provided fertile ground for disease. This can be seen in the instances of bubonic plague and tuberculosis, where urbanization and tight living quarters among the poorer classes respectively contributed to those diseases reaching epidemic status. It can also be seen in the instance of smallpox, where the collision between two previously separate worlds left many of the indigenous population dead. In these instances, social and societal changes resulted in greater ability for the disease to be transmitted between people, and in some instances, to populations who had never been previously exposed allowing the disease to spread like wildfire. Some of these patterns can be seen in the modern-day fight against HIV/AIDS and yearly bouts with influenza viruses. Globalization, along with improved technology, has resulted in increased travel around the world at rapid speed, allowing for HIV/AIDS and new strains of influenza to reach the four corners of the globe.

Of the diseases covered in class, the one I found most interesting was HIV/AIDs, Partly this was due to it being a disease that we will see as medical students and as physicians, partly that it allowed for the promise of applying what we learned about prior epidemics to the modern era. In particular, the instance of how mutations that were protective for past diseases have shown protection against the contraction of HIV/AIDS, demonstrating the interrelatedness in humankind’s eternal struggle against microbial pathogens. Mutations in the delta-32 result in protection against HIV/AIDS, but this trait has served small numbers of people in the past against smallpox and bubonic plague. In tying this finding to the story of Elizabeth Hancock and other plague survivors during 1665, Stephen O’Brien demonstrated that biology and history are two sides of the same coin.

The instance of HIV also demonstrates a convergence of what we know about medicine and science. As Shirwin eloquently states, “In short, scientists in general, and biologists in particular, expect that discoveries from different exploratory paths will

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 20 of 23

converge so that a more complete understanding of the “thing” emerges”. As the de facto most influential infectious disease of the modern era, the research and treatment of HIV represents a convergence of science, contributions from immunology, oncology, microbiology, and public health all contributing to how we understand and treat the disease. Yet, the fight is not finished and the research continues.

The past provides guidelines for the future, and the history of major epidemics is no exception. What we have learned from past epidemics bears weight on how we will respond to future epidemics, whether it be an old foe with new resistance genes or an enemy that is yet unnamed. Along with considering all that we have learned from molecular biology and epidemiology when attempting to prevent an epidemic, it is best practice to consider history as well. While it hard to predict when an epidemic could next occur, we might be well advised to think about what microbial hitchhikers we take with us as we someday create long-term settlements on other planets, once again changing our living conditions and the structure of society.

Major Epidemics in History of Medicine Writeup

Major Epidemics in History of Medicine was a really interesting selective. Because I was taking medical microbiology and immunology during the time of the selective, I immensely enjoyed the historical aspect added to all the diseases I learned to supplement the regular coursework. What I found the most interesting was how epidemics can shape society as a whole. For example, I was fascinated by the fact that the Bubonic plague helped contributed to changing the social structure of Europe from slavery to serfdom, or smallpox was a major cause of the fall of the American empires to the Europeans, or how the Louisiana Purchase was possible due to a yellow fever outbreak. As a medical student, I am often more focused on the pathogenesis, pathophysiology, and treatment of the disease, and I really appreciate the broader perspectives from the readings in class.

As a MD/PhD student, I was more fascinated by the rapid advancement in biomedical science through learning about the epidemics. I enjoyed how as we read, the medical field shifted from Galen medicine to modern medicine. Reading about the accomplishment of Jenner, Pasteur, Yersin, and Koch impressed me on their ability to perform meticulous science. I was most inspired by the HIV reading, where we were able to determine the virus responsible for HIV in three years. Although HIV is still a problem today, our ability to rapidly identify the virus and subsequently prevent death from HIV with early detection made me hopeful. Finally, the selective’s most valuable lesson to me is that we should never underestimate pathogen. Although we live in a golden age of

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 21 of 23

medicine, bacteria, viruses, and parasites can still pose major threats to our civilization. Even though some of the ancient diseases are no longer in our thoughts every day, we may be vastly unprepared for the next dangerous pathogen. Regardless, I take much comfort in the fact that mankind was able to come back from major epidemics time and time again, and each time emerging better than before.

The secondary, yet heinous, effects of epidemics

Epidemics wreak havoc on society, causing widespread mortality accompanied by fear and societal changes. While microbial effects are often more pronounced, directly resulting in sickness and/or death, these effects are predictable and often treatable or preventable. Nearly as harmful, in different manifestations, are the accusations of blame that follow an outbreak. Depending on the region of outbreak, it is often the minority population ends up in the cross hairs of societal blame for the widespread mortality. Across the landscape of major epidemics in history, stochastic events cause outbreaks of disease that are tragically blamed on the minority populations in the absence of a sufficient medical understanding.

Traditionally, it has been stochastic events that have caused an outbreak of disease; the Black Death is a good example. As agricultural technology developed, population levels spiked and people flocked to urban areas. People were living in high densities and there were abundant supplies of food. Life was good. Suddenly, cold weather struck and there was a severe decline in food sources. This led to famine and poverty and now the dense urban centers became a breeding ground for rats and associated microbes. Rats, the primary vector for the Black Death, were forced into close proximity with humans and thus the Black Death epidemic was born. Without a good understanding of the origin of this outbreak, blame was quickly thrown around. Is it interesting to consider whether any human cause is to blame when a time of prosperity followed by a severe stochastic weather event led to the outbreak.

When people looked to assign blame, it was often the minorities that were chosen. Again, we consider the case of the Black Death. Between 1348 and 1350, Jewish populations often resided in ghettos that were isolated from the denser populated regions. Because of this, the Jews were less affected than the larger populations. From this, animosity arose and Jews were accused of poisoning wells. To strike back, the non-Jewish populate massacred and sacked Jewish communities. Interestingly, in this case not only was the outbreak brought on by stochastic reasons, but the salvation of the Jews had stochastic origin. King Casimir of Poland had a Jewish mistress and was friendly towards

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 22 of 23

the group, allowing them refuge. Beyond widespread, microbe-caused death, Jewish populations were targeted as a scapegoat as medical understanding of the plague was missing.

Generally, for most of the time that the Black Death was active, there was uncertainty what or where the contagious agent was. In the 1300s, there was a vague understanding that the Black Death was infectious, but the agent escaped them. It was not until Yersin and Kitasato in the late 1800s and early 1900s that we understood the microbial agent and the rat vector. Without this information earlier, the unknowing led to fear and that led to people making irrational claims about where the disease came from.

While it is deplorable for populations to blame minorities for the outbreak of major epidemics, one might question whether it is useful to assign blame at all. At the time of the outbreaks, fear was rampant and people searched for some way to justify widespread death. A lesson learned might be that in the absence of scientific knowledge, it is best to suspend judgment or belief in something irrational, but still today we see opposition to this idea. No matter the lesson, it is important to consider more than just the pathology of epidemics that struck our world over the past 2000 years. We must also study the secondary, often heinous, effects of epidemics that manifest in unpredictable and unusual ways.

The History of Vaccines and the modern Vaccine Debate

Smallpox, one of the most lethal diseases in the history of humanity, impacted key events in history that led to widespread political and cultural changes, such as the Spanish conquest over the Aztecs. With a rapid disease progression and highly infective aerosol droplets, Smallpox rapidly and mercilessly destroyed susceptible populations. The use of ineffective treatments such as prayer and quack remedies were replaced with variolation in the early 1700s. Although variolation provided lifelong protection from smallpox, it also came with a 2% chance of death due to the infection. It wasn’t until 1796 that a truly revolutionary procedure, now known as vaccination, came to fruition when Edward Jenner administered a small amount of cowpox to a boy, rendering him immune to smallpox.

Despite the overwhelming success of the smallpox vaccine, it was not unanimously welcomed into society. Since the 1830s in America, there has been significant opposition to vaccines for a plethora of reasons. In the 1800s, anti-vaccination supporters frequently had a mistrust of the government and believed that mandatory vaccinations were a “forcible assault” by the ruling class. While some European nations, such as Germany, enacted

M04 579H Major Epidemics in the History of Medicine

Winter 2016

Page 23 of 23

mandatory vaccination laws the U.S. never enacted a federal law making vaccinations mandatory. However, the landmark Johnson vs Massachusetts case in 1905 ruled that a state can enforce vaccinations to protect the public from a communicable disease. In the 1980s, research was indicating a possible link between thimerosal, a preservative previously used in vaccines, and autism. While there have been numerous studies that have since proven no relationship between these vaccines and developmental problems, a widespread mistrust of vaccines still permeates American society.

In addition to the erroneous link with Autism, many individuals in modern society opposed to vaccinations have personal beliefs that lead to vaccine hesitancy. These include: heuristic thinking, the success of vaccination in reducing epidemics leading to the belief that vaccination is now unnecessary, a belief that vaccines are “unnatural”, and a lack of absolute scientific evidence that conclusively proves there is no risk. Due to herd immunity and other modern public health measures, children who are not vaccinated often do not get infected to diseases which they are susceptible, further substantiating the idea that “vaccines are not necessary”. However, vaccine hesitancy can also lead to tragic outbreaks of otherwise preventable diseases, such as the 2015 Disneyland measles outbreak.

As a future physician, it is important to eliminate any predispositions or assumptions about patients who are opposed to vaccination. Instead, as healthcare professionals we should engage in an open conversation with our patients and attempt to understand the source of their hesitancy, dispel any myths, and educate them about the enormous benefit and minimal risk associated with most vaccines. If a patient is still opposed to vaccines, for religious or personal reasons, I believe it is beneficial to still maintain a positive physician-patient relationship so that they feel comfortable reaching out to healthcare professionals when they need assistance.