The End of Plagues

• John Rhodes Cambridge UK

Multco Central . 362.19691 R476e . 2013

• Forward by Sir Richard Sykes

• p001 Introduction

• p005 Ch01 . The Power of the Invisible

• p006 Bubonic plague killed 1/3 of European population between 1348 and 1350

• p006 Great Plague of London 1665-1666

• p008 Ramses V died of smallpox in "1157 BC" (wp 1144 BC)

• p011 Ch02 . Circassian Beauties and Pioneering Women

• p012 Variola major mutated from Variola minor between 400 and 1600 years ago

  • p013 Lady Mary Wortley Montagu née Pierrepont smallpox at 26, championed variolation

• p014 Circassian beauty

• p014 variolation

• p017 Scottish surgeon Charles Maitland innoculated Newgate prisoners in 1722, all survived and were pardoned

• p018 Cotton Mather learned of variolation from slave Onesimus

• p019 Boston doctor Zabdiel Boylston innoculed 242 people during 1721 smallpox outbreak
• p019 smallpox mortality 10% to 30%
• p019 variolation morality 17 out of 897, 2%

• p020 French medical establishment opposed, Voltaire in favor

• p020 Dr. Robert Sutton improved procedure, son Daniel Sutton inoculated 40,000 with 5 deaths

• p021 Thomas Dimsdale

• p021 Catherine the Great innoculated by Thomas Dimsdale, rewarded with "Baron of the Russian Empire"

• p023 Ch03 . The Making of Jenner

• p023 Edward Jenner

• p024 Jenner lodged with surgeon John Hunter

• p026 Jenner found foreign seed in birds, evidence for bird migration
• p026 Jenner observed newly hatched cuckoos push other chicks and eggs out of nest

• p027 observed narrowing and calcification in coronary arteries of angina patients

• p028 1775 siege of Quebec failed when half of the colonial force was infected

• p029 Ch04 Why Not Try the Experiment?

• p030 Cowpox protective against smallpox, dismissed by most doctors, tested by Jenner

• p031 pseudocowpox common, pustules different than cowpox

• p031 True cowpox-infected milkmaid Sarah Nelmes source of pustule, Gloster cow Blossom

• p032 Jenner used "virus" meaning poison or contagion

• p033 Gardener's son James Phipps first innoculated 1796 May 14

  • mild symptoms for 9 days. Very small reaction to variolation, similar to those already exposed and immune

• p034 farmer Benjamin Jesty did the same experiment in 1774, scorned, vindicated in 1805

• p037 Ch05 The Fourth Achievement

• p038 Jenner publishes An Inquiry into the Causes and Effect of the Variolae Vaccinae ... 1798

• p039 James Pearson, hysician at St. George's Hospital
• p043 unlike variolation, cowpox vaccination was not infectious to others
• p044 Parliament awards Jenner ₤10,000 as sole discoverer of vaccination

• p047 Ch06 The Foundling Voyages

• p047 1808 National Vaccine Institute, ₤20,000 awarded to Jenner
• p049 Napoleon ordered 100K francs spent to promote vaccination
• p049 1815 (year of Waterloo battle), French Academy's poetry competition was "Edward Jenner and Vaccination"
• p049 1805 Napoleon releases two imprisoned British scientists at Jenner's request
• p050 vaccination spreads to Latin America, then the Phillipines
• p053 1800 letter to Thomas Jefferson, Monticello vaccinated by August 1801, Virginia, DC, and Philadelphia by year's end

• p055 Ch07 The Teeming Humanity of Nations

• p057 Vaccination did not reach Tibet until the 1940s
• p058 Japanese emperor/Mikado and wife vaccinated in 1875, mandatory nationwide in 1885
• p059 immunity wanes; today boosters at 3 to 10 year intervals

• p059 Vaccination Act 1840

• p065 Ch08 A Great and Loud Commotion

• p065 glycerol and phenol added to vaccines eliminated risk of bacterial infection from vaccines
• p066 Smallpox 1/5 chance of death; 1896 vaccines 1/14,000 chance of death lead to antivaccination resentment

  • Alfred Russell Wallace George Bernard Shaw

• p069 Routine vaccination ended 1971 in Britain

• p071 Ch09 Completing the Picture

• Jenner promotes vaccination for the rest of his life, but uncomfortable in London
• p074 mild stroke age 70, another age 73. died 1823 January 26

• p077 Ch10 Germ Theory and the Birth of Immunology

• p078 Girolamo Fracastoro 1546 theorized fomites

• p079 Antoni van Leeuwenhoek 1632-1723 and Jan Vermeer 1632-1675 lived nearby in Delft

• p080 Herman Boerhaave Louis Pasteur

• p081 Dimitri Ivanovsky Martinus Beijerinck Adelchi Negri Wendell Stanley

• p082 Emil von Behring Kitasato Shibasaburō

• p083 Paul Ehrlich Emile Roux Alexandre Yersin Rudolf Virchow

• p084 Élie Metchnikoff

• p085 Richard Pfeiffer Robert Koch Casimer Davaine

• p086 Ferdinand Cohn

• p087 Felix Haurowitz Friedrich Breinl (1888-1936 Linus Pauling Frank Macfarlane Burnet Niels Jerne Peter Medewar

• p089 Ch11 Victorious Weapons against Illness and Death

• p090 Jenner statue removed from Britannia's Victory Square
  • 1861 Punch Magazine:

    • England's ingratitude still blots

    • The escutcheon of the brave and free;

    • I saved you many million spots

    • And now you grudge one spot for me.

• p090 Moved to Kensington. Author Rhodes says "this is a better place for a man raised in the tranquil Vale of Severn and who was never at home in London.
• p091 Arm-to-arm vaccination no longer used in Europe by 1900, vaccine production in calves instead
• p091 Vaccines against cholera, typhoid, and plague before 1900
• p091 biochemistry term in 1903

• p091 James Sumner isolates, purifies, and crystallizes urease enzyme

• p092 John Keats trained as a surgeon and apothecary

• p092 Keats lost his mother and brother Tom to tuberculosis, led to 1819 Ode to a Nightingale

• p093 Keats died of tuberculosis February 1821

• p094 Robert Koch identified the M. tuberculosis bacteria in 1882

• p095 bacteriologist Albert Calmette 1863-1933 and veterinarian Camille Guerine 1872-1961

• p095 passaging (pronounced pasarging) tuberculosis bacteria 1908 until 1919

• p095 Bacillus Calmette–Guérin (BCG) vaccine tested in humans 1921, 500K infants safely vaccinated

• p095 240 babies vaccinated in Lübeck, all developed acute tuberculosis, 72 died
• p096 Lübeck BCG contaminated with virulent bacillus grown in the same incubator

• p098 six-needle Heaf gun

• p098 ~1/3 of world population has TB, latent for many
• p098 a better vaccine than BG sorely needed

• p101 Ch12 First Light on the Mystery of Infantile Paralysis

• p102 Karl Landsteiner identified cause of polio

• p102 severe polio rare in poor hygiene communities, babies exposed while protected by antibodies in mother's milk

• p103 Simon Flexner and Albert Sabin at Rockefeller Institute in NYC

• p104 Franklin Roosevelt contracted polio at a 1921 Boy Scout jamboree, kept secret for life

• p104 Many new "polios" at Warm Springs Resort in Georgia, Roosevelt arranges separation for convalescents

• p106 radios (battery or wallplug) everywhere in 1938 US, March of Dimes

• p106 Brodie Park 1935 vaccine against polio, inactivation incomplete, some vaccine-related infections

• p107 gastrointestinal virus in humans, only 1% of infections enter the nervous system
• plate 8 Painting of first meeting of the Medical Society of London 1800, with Jenner's image added later

• p109 Ch13 Yearning to Breath Free

• p112 virologist Thomas Rivers led Rockefeller Institute

• p114 Dorothy Horstmann at Yale orally infected monkeys with polio

• p114 Jonas Salk discovered three serotypes of polio using 17000 monkeys

• p115 Isabel Morgan developed a formalin-inactivated-virus vaccine

• p116 Hilary Koprowski tested attenuated live virus vaccines on institutionalized children

• p117 bulbar polio invades cranial nerves that control breathing

• p118 Jonas Salk matriculated to NYU College of medicine, which did not enforce quotas on Jewish studentts
• p119 Salk's 1940's activism against facism and inequality led to future attacks

• p120 Out of This Furnace novel about steelworker unionization

• p120 Salk's lab majority funding for Pittsburg Medical School, test monkey expense

• p123 Ch14 A Great Step Forward

• p123 fearsome Mahoney strain of Salk polio vaccine

• p124 Polk School for the Retarded and Feeble Minded

• p124 Salk worried, prior vaccines were "not happy", but his was safe and produced good antibody levels.
• p126 next, large-scale vaccine trial
• p127 Sabin claimed Salk vaccine not ready for large trial, current infection rates low, a double-blind trial required 500K children for statistically significant results
• p128 socialist medicine dreaded, so no federal or public money involved
• p128 April 4, 1954 news of pathenogenic vaccine batches, testing increased to triple safety checks and 11 consecutive clean lots before any lots passed
• p129 Vaccine Evaluation Center in Ann Arbor ca. 1955

• p130 newly created Department of Health, Education, and Welfare

• p131 Salk said "There is no patent. Could you patent the sun?"

• p132 four polio cases in Idaho, Salk vaccine from Cutter Laboratories

• p133 Cutter problem: clumps of virus in test tube sediment, not inactivated, low quality filters with larger pores
  • modern techniques prevent sedimentation and use better filters

• p133 Sabin tests at Chillicothe Federal Prison

  • incentive $25 and slight sentence reduction, "bored prisoners probably would participate for free"
  • KL but how would prisoner attitude skew the results, with or without incentives?
• p134 Sabin's attenuated viruses grew naturally, stimulated more immune defense than Salk's killed vaccine
• p134 1959, Russia also produced and used Sabin vaccine without mock vaccination or observer controls
• p136 Salk three injection course unpopular, September 1961 HEW chose Sabin vaccine, large scale vaccination in 1962.
• p136 Last US indigenous case of polio in 1979
• p136 Salk said he wouldn't have membership in Salk Institute the if he hadn't founded it himself
• p137 Sabin live-polio vaccine reverts to virulence and causes paralytic polio in 1 of 2.4M vaccine recipients
• p138 First March of Dimes poster child Donald Anderson from Oregon (died 2014 at age of 73)

• p138 Andrew Wyeth 1948 painting Christina's World is of neighbor Anna Christina Olsen (May 3, 1893 – January 27, 1968)

• p139 Ch15 Great Themes and Dirty Little Secrets

• p140 major histocompatibility complex (MHC) found on all cell surfaces in body

• p141 Adjuvants plus microbe protein fragments

• p142 triggers both the innate and adaptive immune system

• p143 Ch16 The War on Influenza

• p143 Herpes virus hides in nerves, emerges as cold sores on skin

• p143 Immune complement system add to adaptive immune system

• p145 Thomas Francis Jr. Salk's mentor

• p145 1918 influenza first case Albert Gitchell(WP) Mitchell(book) at Camp Funston KS

• p146 perhaps 1915-1916 in France?
• p146 perhaps after 1916-1917 Battle of the Somme, soldiers at Étaples camp turned blue and died
• p146 similar outbreak two months later at Aldershot camp in England
• p148 October 1918, 195,000 died of influenza in the United States
• p148 Estimated 50 million killed worldwide

• p149 1997 samples from Brevig Alaska permafrost grave yielded virus and complete genome Taubenberger 2008 Taubenberger 2019

• p150 New live vaccines only grow in nose and throat, at temperatures lower than 25C, destroyed by warmer lung temperatures

  • KL unless they mutate and adapt

• p150 Universal vaccine for all flu types that attack hidden region of H spike shared by all subtypes

  • KL unless that region mutates and adapts

• p152 March 1947 Eugene Le Bar dies of atypical smallpox

• p151 Ch17 Forged in the Crucible of War

• p152 March 1947 Eugene Le Bar dies of atypical smallpox
• p153 12 other cases emerge - HUGE response, 6 million vaccination
• p153 vaccination blamed for other illnesses
• p154 no more cases beyond the first 12

• p154 Dr. Fred Soper, hemisphere wide campaign to eradicate smallpox

• p154 May 1958 Soviet deputy minister of health Viktor Zhdanov concurred

• p155 WHO global Eradication campaign began February 1966

• p155 African and Asian surveys revealed that less than 5% of smallpox cases officially reported
• p155 not 130K but 2.5M cases, more than 200M doses needed

• p157 William Foege

• p139 Ch18 Smallpox in a Land of Ancient Wisdom

• p160 Smallpox campaigns missed inaccessible rural populations, instead revaccinated closer people
• p160 In 1967, 83,000 cases reported, only 10% of real total

• p160 1968 forked needle repurposed by Donald Henderson

• p161 surveillance-containment instead of passive waiting for patient reporting
• p162 manpower costly; 5000 new cases in Bihar required 50,000 to deal with them
• p162 un-vaccinated children attending funeral at friend's home all develop smallpox ten days later
• p163 Smiling Buddha nuclear test complicates US response
• p164 villager says: when house catches fire, use all water on that, don't waste time on other houses
• p166 villager resistance to vaccination replaced by cordial hospitality

• p166 May 24 1975 last reported case in town of Karimganj (book spells this Karaminganj)

• p167 Ch19 The Final Defeat of Smallpox

  • campaign in Bangladesh, stymied by Bengali authorities
• p168 Dhaka slums bulldozed, 400K people spread across country, many infected with smallpox

• p168 side comment: Bangladesh Bhola Island partly inundated by sea level rise, 500,000 now homeless. world's first climate change refugees

• p169 More than half of Ethiopians live more than a day's journey from any road. Variola minor was endemic

• p172 1976 smallpox outbreak in Somalia

• p173 Ch20 Invisible Weapons of War

• p176 Biopreparat still worked on weaponized smallpox in 1992
• p176 former director Kanatjan Alibekov defected to the west and revealed that former researchers sold samples to rogue states

• p177 Some herpes? antivirals effective against smallpox: tecovirimat / Tpoxx (for orthoviruses), brincidofovir / Texemba (for smallpox), and cidofovir / Vistide (for cytomegalovirus)

• p177 smallpox vaccine propagated in cows. ???The vaccine used in the eradication campaign is not smallpox???
  • what does that mean?
• p178 vaccinia may have originated from horsepox

• p178 housecats most often infects human owners with this historic virus (presumably cowpox)

• p179 Ch21 Benefits, Risks, and Fears

• p179 Arthur Allen, Vaccine: The Controversial History of Medicine's Greatest Lifesaver, 2007 (WCCLS, Forest Grove)

• p183 Maurice Hillman "rational empiricism", informally guts and guesses

• p185 GlaxoSmithKline vaccine for infant diarrhea established(?) in Brazil and Mexico where need was high

• p186 "Pertussis" name for whooping cough vaccine, bacterium "Bordella pertussis"

• p186 pertussis component of DTP vaccine causes problems

• p187 poorly understood adjuvants may have been responsible past for vaccine damage

• p187 Yuji Sato 1981 DTaP, though cheaper DTP is still used

• p188 no population-level association between MMR and autism, not enough precision to detect rare events
• p188 treatment of unrecognized intestinal problems may help developmentally disabled children
• p189 Antivaccine groups continued blaming thimerosal long after it was removed from children's vaccines
• p189 six ways vaccines can cause harm:
  • Killed vaccines may be contaminated with live vaccinal virus
  • vaccines may carry hidden passenger viruses
  • components of vaccines may provoke adverse reactions
  • live attenuated viruses may (in a tiny minority) cause the disease they are intended to prevent
  • vaccines may simply be ineffective, or unwanted by those compelled to receive them
  • otherwise safe vaccines my overwhelm weakened immune systems of the immunocompromised

• p191 Ch22 Inspiration in the Global Village

• p193 providing vaccines to the neediest one of the greatest challenges
• p194 Immune responses triggered by HIV help the infection, because the virus resides in immune cells
• p195 pathogens (like HIV and malaria) that change their antigens are difficult vaccine targets

• p195 adenovirus carrier for HIV vaccine proteins

• p196 heterologous prime-boost regimen

• p196 A sporozoite is the cell form that infects new hosts.
• p196 Newborns are protected by maternal antibodies in breast milk
• p198 malaria sporozoites synthesized in yeast may be used in vaccines against African malaria

• p198 Global Polio Eradication Initiative GEPI, type 2 already eliminated.

• p199 Ch23 A Team of Many Colors

• p200 prebendary customs: in some cultures, elected officials believe they own a personal share of government revenues

• p201 Olusegun Obasanjo targeted polio

  • muslims in other areas assumed conspiracy because malaria, cholera, diarrheal vaccines were expensive
• p203 stories of turnaround and trust in Africa

• p204 Supplemental Immunization Activities

  • vaccines to every household, even if past vaccinations,
• p206 High energy xray imaging of viruses helps design synthetic shells empty of genetic material
• p206 polio 99% eradicated, 2.5 billion children vaccinated
• p209 Central Africa at high risk because 10 million nomads migrate through northern Nigeria and its neighbors
• p213 China polio-free after 1994?1999, new case appeared in 2011 in southern Xinjiang Uyghur Autonomous region.
  • public health emergency declared, 5 million vaccine doses airlifted, 500,000 volunteers went house to house vaccinating everyone.

• p215 Ch24 The Milkmaid and the Cuckoo

• p215 1933 Cambridge University Library

• p216 Jakov Heine first described polio in 1840

• p216 Bacillus Calmette–Guérin (BCG) vaccine for tuberculosis, second vaccine from cows