Innovation & Re-Invention: Connaught Laboratories, Biotechnology & Canadian Public Health Tuesday, September 7, 2010 FitzG...
A Legacy of Re-Invention
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Heal...
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Heal...
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Heal...
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Heal...
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Heal...
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Heal...
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance 1956-1972  – DPT-Polio, Pande...
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance 1956-1972  –  DPT-Polio, Pand...
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance 1956-1972  –  DPT-Polio, Pand...
Overview:  Connaught’s Historical Contributions: Biological Products of Medical Significance 1956-1972  –  DPT-Polio, Pand...
Key Global & Canadian Public Health Foundations, 1882-1910 Prelude: 1796 - Edward Jenner demonstrated immunizing value of ...
Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in ...
Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in ...
Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in ...
Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in ...
Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in ...
Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) Ontar...
Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) 1886 ...
Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) 1886 ...
Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) 1886 ...
Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) 1886 ...
Origins
Dr. John G. FitzGerald (1882-1940):  Canada’s Public Health Visionary <ul><li>1903 –  Youngest to graduate from University...
Dr. John G. FitzGerald (1882-1940):  Canada’s Public Health Visionary <ul><li>Spring 1913  - Joins Ontario Provincial Labo...
Antitoxin Laboratories: Birthplace in a Backyard, December 1913 <ul><li>Barton Avenue Sable </li></ul><ul><li>Dr. FitzGera...
May 1, 1914 -  University of Toronto Signs On <ul><li>On May 1, 1914, the University of Toronto Board of Governors assumed...
Target Diphtheria:  Antitoxin Attack Tames ‘The Strangler’ <ul><li>The primary mission of the new Antitoxin Laboratories w...
World War I Expansion: Christening of “Connaught” Laboratories, 1917 <ul><li>WWI Tetanus Antitoxin crisis prompts expansio...
World War I Expansion
Smallpox Vaccine
<ul><li>Growing demand for high quality Canadian supply of smallpox vaccine prompts Antitoxin Laboratories to purchase cat...
Vaccines & Antitoxins Supplied to Canada & the World <ul><li>Vaccines are a global enterprise </li></ul><ul><li>This has b...
Influenza:  Facing a Pandemic  (Part I)
1918-19: Influenza Pandemic <ul><li>More than 50,000 deaths in Canada, with 10,000 in Ontario </li></ul><ul><li>50 million...
<ul><li>Scientists had first targeted a bacterium,  B. influenza , as the cause of influenza and then prepared a vaccine b...
<ul><li>Due to this unprecedented emergency, Connaught made no claims for the effectiveness of the vaccine, but kept caref...
Insulin:  The ‘Greatest’ Invention
<ul><li>Insulin was recently voted the Greatest Canadian Invention </li></ul>Originally aired on CBC-TV Jan 3, 2007 Insuli...
<ul><li>Insulin was recently voted the Greatest Canadian Invention </li></ul><ul><li>Dr. Frederick Banting, the primary di...
<ul><li>Insulin was recently voted the Greatest Canadian Invention </li></ul><ul><li>Dr. Frederick Banting, the primary di...
<ul><li>Banting and his student partner, Charles Best, discovered Insulin in a small laboratory on the roof of the Univers...
<ul><li>By January 1922, the main focus of the insulin story had shifted downstairs in the Medical Building to Connaught’s...
<ul><li>By May 1923, Connaught’s Insulin production had grown significantly after expanded facilities were installed into ...
Insulin:  The ‘Greatest’ Invention To learn more about the discovery, development & legacy of the Discovery of Insulin in ...
The School of Hygiene: Connaught HQ, 1927-1955 The discovery of Insulin drew considerable international attention to the U...
Diphtheria Toxoid:  Taming ‘The Strangler’
Diphtheria Toxoid:  Taming ‘The Strangler’ <ul><li>Eighty years ago, Canada led the world’s public health war against one ...
Diphtheria Toxoid:  Taming ‘The Strangler’ <ul><li>The key to victory was diphtheria toxoid, discovered by Dr. Gaston Ramo...
Diphtheria Toxoid:  Taming ‘The Strangler’ <ul><li>Landmark Diphtheria Toxoid field trials took place in many Ontario citi...
Diphtheria Toxoid:  Taming ‘The Strangler’ <ul><li>During the 1930s and 1940s, armed with this very effective new vaccine,...
Pertussis:  Preventing ‘Whooping Cough’
Pertussis:  Preventing ‘Whooping Cough’ <ul><li>1906  - The infection-causing bacterium first isolated and cultured by Bel...
Pertussis:  Preventing ‘Whooping Cough’ <ul><li>1931 - 32  - Encouraged by the work of Madsen and Sauer, Dr Nelles Silvert...
Pertussis:  Preventing ‘Whooping Cough’ <ul><li>1936 - 37  - With such encouraging results, Connaught's fresh strain Pertu...
Pertussis:  Preventing ‘Whooping Cough’ <ul><li>Connaught's fresh strain Pertussis Vaccine was originally produced by cult...
Pertussis:  Preventing ‘Whooping Cough’ Dr L.N. Farrell & Edith Taylor <ul><li>Working with Drs. Leone Farrell & Edith Tay...
DP:  1 st  Pediatric Combination Vaccine <ul><li>The introduction of fresh strain Pertussis Vaccine created a new challeng...
DPT:  Foundation of Pediatric Combination Vaccines <ul><li>1946  - Building on the success of Tetanus Toxoid at the front ...
Connaught & World War II: Penicillin:  Making the Miracle Drug
Penicillin:  Making   the Miracle Drug <ul><li>1928  – Discovered by Dr. Alexander Fleming at St. Mary’s Hospital, London,...
Penicillin:  Making   the Miracle Drug <ul><li>1941-43  – After Dr. H.W. Florey visited Canada and the U.S., researchers a...
Penicillin:  Making   the Miracle Drug <ul><li>April 1944 –  After extensive renovations, penicillin production began in w...
Penicillin:  Making   the Miracle Drug <ul><li>Nov 1945 –  A significantly more efficient “Submerged Culture” penicillin p...
Other WWII Efforts:  Influenza Vaccine <ul><li>1933  - Influenza virus types A and B (with various sub-strains) first isol...
Conquering The Crippler: Connaught & Polio Vaccines
Connaught & Polio Vaccines:  Key Global & Canadian Research Foundations <ul><li>1908 –  Poliovirus first isolated </li></u...
Connaught & Polio Vaccines:  Key Global & Canadian Research Foundations <ul><li>1947  -  Dr. A.J. Rhodes (right) launches ...
16 “ Medium 199”:  The 1st Synthetic Media & Connaught’s Breakthrough Coincidence Morton Morgan Parker <ul><li>1949  - Con...
Dr Arthur E. Franklin “ Medium 199” The Key to Poliovirus Growth <ul><li>1950-51 - Using Ender’s methods, Rhodes was growi...
Dr. Jonas E. Salk: Vaccine Pioneer @ University of Pittsburgh <ul><li>In the meantime, by 1951, Dr. Jonas Salk had shown t...
“ The Toronto Method” Facilitating Large Scale Poliovirus Production <ul><li>1952  - Recognizing Connaught’s experience in...
Salk Polio Vaccine Field Trial: Connaught Supplies Poliovirus Fluids <ul><li>July 1953  - In the wake of the worst polio e...
April 24, 1954:  Launch of Salk Vaccine Field trial <ul><li>1,800,000 children enrolled across U.S; in May Alberta, Manito...
April 12, 1955: “V-Day” Salk Vaccine Trial Results Announced <ul><li>April 12, 1955  – Unprecedented media attention to an...
Connaught Provides Salk Vaccine to the World <ul><li>Soon, Connaught was exporting Salk vaccine to some 44 other countries...
<ul><li>1959  – Building on the DP and DPT models designed to minimize injections, Connaught pioneered a new generation of...
Connaught & Polio Vaccines:  Leadership in Oral Polio Vaccine Development <ul><li>1959  - Seed pools were provided by Dr A...
Connaught Provides Sabin Vaccine to the World <ul><li>1961  - Connaught supplies 3 million doses of OPV to Japan to bring ...
Connaught & Polio Vaccines:  Advances in Polio Vaccine Production <ul><li>1965  – Purified concentrated IPV </li></ul><ul>...
Influenza:  Facing a Pandemic  (Part II)
<ul><li>Late 1956  – WHO network of Influenza Centres  tracked the spread of an epidemic from eastern Asia to Europe and N...
<ul><li>Early Oct 1957  – With production at 10,000 doses per week, Connaught delivers 400,000 doses of influenza vaccine,...
Slaying the Speckled Monster: Connaught & Smallpox Eradication
Making “The Best Smallpox Vaccine in this Galaxy” Connaught and Smallpox Vaccine Improvements <ul><li>1957-58  - Major sma...
Making “The Best Smallpox Vaccine in this Galaxy” Connaught and Smallpox Vaccine Improvements <ul><li>1962  – Dr. Paul Fen...
<ul><li>1967-68  – Drs. Paul Fenje and R.J. Wilson of Connaught begin consulting work in South America to improve the qual...
Using “The Best Smallpox Vaccine in this Galaxy” Connaught and Smallpox Eradication <ul><li>1970-74  –  Canadian governmen...
Using “The Best Smallpox Vaccine in this Galaxy” Connaught and Smallpox Eradication <ul><li>Oct 1977  – Last natural case ...
2001-2003 - History Repeats Itself: Meeting the New Smallpox Bio-terrorism Threat <ul><li>Sept 11, 2001  – Fear of Smallpo...
“ Too Big For Canada, Too Small for the World” Connaught’s Privatization & Global Partnerships, 1972-1989
Connaught For Sale: Privatization & Transformation <ul><li>Late 1960s –  “Winds of change” blowing through University of T...
Connaught For Sale: Privatization & Transformation <ul><li>1972 –  Canadian Development Corporation (CDC) offers $25 milli...
Connaught Laboratories Limited: Consolidations & Expansions <ul><li>1972 – 1979 –  Challenging period for Connaught, marke...
Connaught Laboratories Incorporated: U.S. Expansion in Swiftwater, PA <ul><li>1896 –  Pocono Laboratories established by D...
Connaught Laboratories Incorporated: U.S. Expansion in Swiftwater, PA <ul><li>1975 – 1977 –  Dr.   Jonas Salk publicly exp...
Connaught’s Canadian & International Partnerships, 1980s <ul><li>In addition to the creation of the Connaught Laboratories...
Connaught’s Shifting Ownership: The Road to France <ul><li>1984  - Canadian Development Corporation (CDC) sold 34% of its ...
Connaught’s Shifting Ownership: The Road to France <ul><li>1988  - After two years of unsuccessful merger discussions, Ins...
Connaught’s Shifting Ownership: The Road to France <ul><li>1897 -  Institut Merieux  (IM) created in Lyon, France, by Marc...
Building the Best Vaccine Combinations
<ul><li>1988  - ProHibit launched, providing protection against  Haemophilus influenzae b  (or Hib) - the leading cause me...
Connaught’s PENTA Team PENTA Launch, with Jonas Salk (right) participating remotely <ul><li>The World’s first modern 5-com...
5-Component Acellular Pertussis Vaccine Creating the Gold Standard in Canada <ul><li>1980s  – Connaught team of scientists...
Pentacel quickly becomes universally used across Canada, effectively enabling the replacement of OPV with IPV in all provi...
Increase in adolescent pertussis with decrease in infant pertussis New Challenges:  Adolescent and Adult Pertussis Adolesc...
<ul><li>The world’s first vaccine for adolescents and adults containing 5-component acellular Pertussis Vaccine in combina...
5-Component Pertussis Combinations <ul><li>Pentacel </li></ul><ul><li>Pediacel  (fully liquid form of Pentacel) </li></ul>...
From Aventis Pasteur to Sanofi Pasteur: Maintaining Connaught’s Canadian Identity into the 21 st  Century
Canada & Global Biotech Partnerships:  Connaught & the Creation of Aventis Pasteur <ul><li>Rhone-Poulenc </li></ul><ul><li...
Canada & Global Biotech Partnerships:  Connaught & the Creation of sanofi pasteur <ul><li>Sanofi: </li></ul><ul><li>1973 -...
Sanofi Pasteur: The Broadest Range of Vaccines Worldwide Bacterial diseases Pertussis Diphtheria Haemophilus influenzae  b...
Connaught Campus Recent Investments <ul><li>Warehouse (2000)  $15 M </li></ul><ul><li>Component Pertussis (5cP) (2003)  $1...
Showcasing a Unique Heritage Barton Avenue Stable - 1913 - 2001
Showcasing a Unique Heritage 2004
Showcasing a Unique Heritage Heritage Centre 2004 - 2010
Sources & Resources <ul><li>Archives, Sanofi Pasteur Limited  (Connaught Campus), Toronto </li></ul><ul><li>Health Heritag...
Acknowledgements <ul><li>This presentation is based on academic and professional research on the history of Connaught Labo...
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Innovation and Re-Invention: Connaught Laboratories, Biotechnology and Canadian Public Health

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Presentation prepared for 2010 Incoming Class @ Dalla Lana School of Public Health, University of Toronto, September 7, 2010

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  • Slide 6 1916-17 – Canada gets serious about Smallpox Vaccine   -          Connaught assumed responsibility for smallpox vaccine production in 1916, acquiring the assets of the Ontario Vaccine Farm, which had been producing vaccine in Palmerston since 1885   -          Connaught helped by the New York City Health Department Laboratory getting production started with supplies of an original Jenner Vaccinia strain and bulk vaccine to meet immediate Canadian demands   -          Connaught’s full vaccine production began in 1917. Most of its first lots supplied to the Canadian Armed Services, and then, shortly after the war, to fight major smallpox outbreaks in the Toronto and Ottawa areas
  • While smallpox vaccine was a very effective weapon to prevent that disease, the great influenza pandemic of 1918-19 brought Connaught scientists face to face with a deadly infectious threat that could not be prevented with a vaccine, despite a valiant effort to try to prepare one during the peak of the emergency. Not unlike the recent experience with SARS in Toronto and elsewhere, especially in China, during the influenza pandemic there were frantic efforts to identify the cause of the disease and hopefully prepare a vaccine that might prevent it. Scientists had first targeted a bacterium, B. influenza , as the cause of influenza in 1892 and then prepared a vaccine based on a variety of strains isolated from influenza cases. When the epidemic started in 1918, the New York City Health Department prepared such a vaccine and supplied what were thought to be influenza strains to Connaught for preparing a Canadian vaccine.
  • Working day and night in the cramped Antitoxin Laboratory in the University of Toronto Medical Building basement, a small team under the direction of Dr. R.D. Defries, supplied the Connaught influenza vaccine in large quantities, and free of charge, to provincial health departments, hospitals, the military and other public health services across the country. Due to this unprecedented emergency, Connaught made no claims for the effectiveness of the vaccine, but kept careful records so that it could be evaluated. However, as the epidemic eased it became increasingly clear that the influenza bacterium was not responsible for the disease, but, as was discovered in 1933, it was due to a virus.
  • Slide 17 1967-68 – Energizing Smallpox Eradication   -          In 1966, the WHO turned to Connaught to serve as one of two International Smallpox Vaccine Reference Centers for the global eradication campaign. The second Reference Center was located at the RIJKS Institute in the Netherlands   - In 1967 the Pan American Health Organization asked Drs Fenje and R.J. Wilson to serve as consultants to help local smallpox vaccine producers in South America improve the quality of their vaccine.
  • Innovation and Re-Invention: Connaught Laboratories, Biotechnology and Canadian Public Health

    1. 1. Innovation & Re-Invention: Connaught Laboratories, Biotechnology & Canadian Public Health Tuesday, September 7, 2010 FitzGerald Building Room 103 Introduction to CHL 5004 for Incoming Class Dalla Lana School of Public Health, University of Toronto By Christopher J. Rutty, Ph.D. Medical Historian, Consultant Health Heritage Research Services http://healthheritageresearch.com
    2. 2. A Legacy of Re-Invention
    3. 3. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Health Foundations, 1882-1910 Louis Pasteur
    4. 4. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Health Foundations, 1882-1910 Origins – Dr. J.G. FitzGerald’s Public Health Vision
    5. 5. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Health Foundations, 1882-1910 Origins – Dr. J.G. FitzGerald’s Public Health Vision 1914-1921 – Antitoxins, WWI, Smallpox & Pandemic Influenza Vaccines
    6. 6. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Health Foundations, 1882-1910 Origins – Dr. J.G. FitzGerald’s Public Health Vision 1914-1921 – Antitoxins, WWI, Smallpox & Pandemic Influenza Vaccines 1922-1940 – Insulin, Diphtheria &, Pertussis Vaccines
    7. 7. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Health Foundations, 1882-1910 Origins – Dr. J.G. FitzGerald’s Public Health Vision 1914-1921 – Antitoxins, WWI, Smallpox & Pandemic Influenza Vaccines 1922-1940 – Insulin, Diphtheria &, Pertussis Vaccines 1941-1945 – WWII, Penicillin & 1 st Pediatric DP & DPT Combination Vaccines
    8. 8. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance Global & Canadian Public Health Foundations, 1882-1910 Origins – Dr. J.G. FitzGerald’s Public Health Vision 1914-1921 – Antitoxins, WWI, Smallpox & Pandemic Influenza Vaccines 1922-1940 – Insulin, Diphtheria &, Pertussis Vaccines 1941-1945 – WWII, Penicillin & 1 st Pediatric DP & DPT Combination Vaccines 1946-1955 – Virus Research, Synthetic Media & Salk Polio Vaccine
    9. 9. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance 1956-1972 – DPT-Polio, Pandemic Influenza, Sabin Polio, & Smallpox Eradication
    10. 10. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance 1956-1972 – DPT-Polio, Pandemic Influenza, Sabin Polio & Smallpox Eradication 1972-1989 – University of Toronto Sale, Swiftwater Acquisition, New Partnerships
    11. 11. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance 1956-1972 – DPT-Polio, Pandemic Influenza, Sabin Polio & Smallpox Eradication 1972-1989 – University of Toronto Sale, Swiftwater Acquisition, New Partnerships 1989-1999 – Institute Mérieux Takeover, New Vaccine Combinations, Acellular Pertussis and Pentacel, Aventis Pasteur Creation
    12. 12. Overview: Connaught’s Historical Contributions: Biological Products of Medical Significance 1956-1972 – DPT-Polio, Pandemic Influenza, Sabin Polio & Smallpox Eradication 1972-1989 – University of Toronto Sale, Swiftwater Acquisition, New Partnerships 1989-1999 – Institute Merieux Takeover, New Vaccine Combinations, Acellular Pertussis and Pentacel, Aventis Pasteur Creation 2000-2010 – Sanofi Pasteur Creation, Showcasing a Unique Legacy
    13. 13. Key Global & Canadian Public Health Foundations, 1882-1910 Prelude: 1796 - Edward Jenner demonstrated immunizing value of Smallpox Vaccine
    14. 14. Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in France Prelude: 1796 - Edward Jenner demonstrated immunizing value of Smallpox Vaccine
    15. 15. Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in France 1888 - Pasteur Institute founded in Paris Prelude: 1796 - Edward Jenner demonstrated immunizing value of Smallpox Vaccine
    16. 16. Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in France 1888 - Pasteur Institute founded in Paris 1890 - Diphtheria Antitoxin discovered by Emil Behring in Germany Dr Emil Behring Prelude: 1796 - Edward Jenner demonstrated immunizing value of Smallpox Vaccine
    17. 17. Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in France 1888 - Pasteur Institute founded in Paris 1890 - Diphtheria Antitoxin discovered by Emil Behring in Germany 1891 – Lister Institute of Preventive Medicine established in Great Britain Dr Joseph Lister Prelude: 1796 - Edward Jenner demonstrated immunizing value of Smallpox Vaccine
    18. 18. Key Global & Canadian Public Health Foundations, 1882-1910 1885 - Pasteur Rabies Treatment discovered by Louis Pasteur in France 1888 - Pasteur Institute founded in Paris 1890 - Diphtheria Antitoxin discovered by Emil Behring in Germany 1891 – Lister Institute of Preventive Medicine established in Great Britain 1895 - New York City Public Health Laboratories created Dr William H. Park, Director, NYC Public Health Laboratories Prelude: 1796 - Edward Jenner demonstrated immunizing value of Smallpox Vaccine
    19. 19. Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) Ontario Legislature, Queen’s Park, Toronto
    20. 20. Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) 1886 - Ontario Smallpox Vaccine Farm established in Palmerston
    21. 21. Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) 1886 - Ontario Smallpox Vaccine Farm established in Palmerston 1890 - Ontario Provincial Laboratory established (1st in North America) Ontario Public Health Laboratories, 5 Queen’s Park Circle, Toronto
    22. 22. Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) 1886 - Ontario Smallpox Vaccine Farm established in Palmerston 1890 - Ontario Provincial Laboratory established (1st in North America) 1910 - Department of Hygiene, University of Toronto, established Dr J.A. Amyot, 1 st Professor of Hygiene, U. of T. & Director, Ontario Board of Health Laboratory U. Of T. Dept. of Hygiene had a Museum of Hygiene behind this door
    23. 23. Key Global & Canadian Public Health Foundations, 1882-1910 1882 - Ontario Provincial Board of Health (1st in Canada) 1886 - Ontario Smallpox Vaccine Farm established in Palmerston 1890 - Ontario Provincial Laboratory established (1st in North America) 1910 - Department of Hygiene, University of Toronto, established 1910 - Canadian Pubic Health Association founded, Duke of Connaught, first patron For more background visit: http://cpha100.ca eBook: This Is Public Health: A Canadian History
    24. 24. Origins
    25. 25. Dr. John G. FitzGerald (1882-1940): Canada’s Public Health Visionary <ul><li>1903 – Youngest to graduate from University of Toronto Medical School </li></ul><ul><li>1908-1911 - Extensive bacteriological education in Canada, the U.S. and Europe, including at the Pasteur Institute in Brussels, the Lister Institute in the U.K., and the New York City Department of Health </li></ul>Dr J.G. FitzGerald (right) @ the Pasteur Institute, Brussels, 1910 <ul><li>FitzGerald was determined to bring the life-saving benefits of new antitoxins and vaccines within the reach of all Canadians. </li></ul>
    26. 26. Dr. John G. FitzGerald (1882-1940): Canada’s Public Health Visionary <ul><li>Spring 1913 - Joins Ontario Provincial Laboratory to prepare Pasteur Rabies Treatment, assisted by William “Billy” Fenton </li></ul><ul><li>Fall 1913 – Appointed Associate Professor of Hygiene at University of Toronto </li></ul>Medical School, University of Toronto <ul><li>Disturbed by high cost of imported diphtheria antitoxin and other essential public health products, FitzGerald investigated how to prepare and distribute them in Canada as a public service </li></ul>
    27. 27. Antitoxin Laboratories: Birthplace in a Backyard, December 1913 <ul><li>Barton Avenue Sable </li></ul><ul><li>Dr. FitzGerald hoped for University of Toronto support in the production of public health antitoxins and vaccines </li></ul><ul><li>In the meantime, in late 1913, Dr FitzGerald built a modest horse stable & laboratory in Fenton’s backyard on Barton Avenue in west Toronto to prepare Diphtheria Antitoxin </li></ul><ul><li>Diphtheria Antitoxin provided passive immunity to the disease utilizing the immune sera of horses </li></ul>Located in a backyard at 145 Barton Avenue, near Christie & Bloor Streets in west Toronto
    28. 28. May 1, 1914 - University of Toronto Signs On <ul><li>On May 1, 1914, the University of Toronto Board of Governors assumed responsibility for Dr. FitzGerald’s Antitoxin Laboratories, providing space in the Medical Building basement </li></ul><ul><li>Dr. FitzGerald’s Director’s Office (left) & First Laboratory Room (below), which accommodated all of the work of the new Laboratories during its first year </li></ul>
    29. 29. Target Diphtheria: Antitoxin Attack Tames ‘The Strangler’ <ul><li>The primary mission of the new Antitoxin Laboratories was preparing Diphtheria Antitoxin and providing it as a public service at cost to Provincial Health Departments for free distribution to diphtheria patients; declining diphtheria death rates underscore its success </li></ul>
    30. 30. World War I Expansion: Christening of “Connaught” Laboratories, 1917 <ul><li>WWI Tetanus Antitoxin crisis prompts expansion of Antitoxin Laboratories to a vacant “Farm” site in north Toronto, donated by Col. A.E. Gooderham (below) </li></ul><ul><li>Laboratories officially named “Connaught” after Duke of Connaught, public health patron and wartime Governor General of Canada </li></ul><ul><li>“ Connaught Antitoxin Laboratories and University Farm” officially opened October 25, 1917 </li></ul>
    31. 31. World War I Expansion
    32. 32. Smallpox Vaccine
    33. 33. <ul><li>Growing demand for high quality Canadian supply of smallpox vaccine prompts Antitoxin Laboratories to purchase cattle & equipment from Ontario Vaccine Farm </li></ul><ul><li>Initial Smallpox virus seed and bulk vaccine supplied from New York City Health Department Laboratories </li></ul><ul><li>Connaught’s Smallpox vaccine production begins with harvest of first vaccinia pulp </li></ul><ul><li>First lot of vaccine released in Dec 1917. </li></ul><ul><li>Connaught supplies more than 600,000 doses of vaccine to Canadian military by end of WWI </li></ul><ul><li>Connaught supplies 1 million doses of vaccine to control serious smallpox outbreaks in Ontario </li></ul>1916: Connaught Launches Smallpox Vaccine Connaught’s smallpox vaccine was produced in front left corner rooms of Building #3 from 1917 to 1950. 1916 1917 1918 1921 1919 1920 Early bio-reactor – 4 legged model
    34. 34. Vaccines & Antitoxins Supplied to Canada & the World <ul><li>Vaccines are a global enterprise </li></ul><ul><li>This has been true for Connaught since World War I </li></ul>
    35. 35. Influenza: Facing a Pandemic (Part I)
    36. 36. 1918-19: Influenza Pandemic <ul><li>More than 50,000 deaths in Canada, with 10,000 in Ontario </li></ul><ul><li>50 million deaths globally </li></ul>
    37. 37. <ul><li>Scientists had first targeted a bacterium, B. influenza , as the cause of influenza and then prepared a vaccine based on a variety of strains isolated from influenza cases. </li></ul><ul><li>Working day and night in a cramped lab, a small team under the direction of Dr. Robert D. Defries, supplied Connaught’s influenza vaccine free of charge to provincial health departments, hospitals, the military and other public health services across the country. </li></ul>Connaught Supplies Influenza Vaccine to the Nation <ul><li>During the pandemic there were frantic efforts to identify the cause of the disease and hopefully prepare a vaccine that might prevent it. </li></ul>
    38. 38. <ul><li>Due to this unprecedented emergency, Connaught made no claims for the effectiveness of the vaccine, but kept careful records so that it could be evaluated </li></ul>Connaught’s efforts were greatly appreciated by provincial health departments, as well as by the newly established Department of National Health in Ottawa, its creation in 1919, in large part attributed to the pandemic. Connaught Supplies Influenza Vaccine to the Nation
    39. 39. Insulin: The ‘Greatest’ Invention
    40. 40. <ul><li>Insulin was recently voted the Greatest Canadian Invention </li></ul>Originally aired on CBC-TV Jan 3, 2007 Insulin: The ‘Greatest’ Invention
    41. 41. <ul><li>Insulin was recently voted the Greatest Canadian Invention </li></ul><ul><li>Dr. Frederick Banting, the primary discoverer of Insulin, was also named the 4 th Greatest Canadian in history </li></ul>Aired on CBC-TV on Nov 28 and 29, 2004 Insulin: The ‘Greatest’ Invention
    42. 42. <ul><li>Insulin was recently voted the Greatest Canadian Invention </li></ul><ul><li>Dr. Frederick Banting, the primary discoverer of Insulin was also named the 4 th Greatest Canadian in history </li></ul><ul><li>Insulin was perhaps the greatest invention in the history of Connaught Laboratories </li></ul>Insulin: The ‘Greatest’ Invention
    43. 43. <ul><li>Banting and his student partner, Charles Best, discovered Insulin in a small laboratory on the roof of the University of Toronto Medical Building in the summer of 1921 </li></ul>Insulin: The ‘Greatest’ Invention
    44. 44. <ul><li>By January 1922, the main focus of the insulin story had shifted downstairs in the Medical Building to Connaught’s basement labs where Best personally oversaw the development of methods to prepare insulin on a large scale </li></ul><ul><li>Expediting this Insulin development work and expanding its production scale was made possible through close co-operation between Connaught and Eli Lilly & Co. of Indianapolis </li></ul>Insulin: The ‘Greatest’ Invention
    45. 45. <ul><li>By May 1923, Connaught’s Insulin production had grown significantly after expanded facilities were installed into what had been the U of T’s YMCA building. </li></ul><ul><li>In 1927, Connaught’s Insulin production capacity expanded still further when its Insulin Plant opened in one wing of the new School of Hygiene Building constructed not far from where the old YMCA Building stood </li></ul>Insulin: The ‘Greatest’ Invention Through a unique patent arrangement between the discoverers of Insulin and the University of Toronto’s Insulin Committee, Connaught assumed the public trust of supplying all of Canada’s Insulin needs at the lowest possible price
    46. 46. Insulin: The ‘Greatest’ Invention To learn more about the discovery, development & legacy of the Discovery of Insulin in Toronto, visit the poster exhibit outside the Diabetes Clinic at Toronto General Hospital, 12th floor, Eaton Wing. Posters also viewable at: http://healthheritageresearch.com
    47. 47. The School of Hygiene: Connaught HQ, 1927-1955 The discovery of Insulin drew considerable international attention to the U of T, particularly from the Rockefeller Foundation in New York In 1925, the foundation provided funding for the establishment of a School of Hygiene for the expansion of public health education, and also to provide new research, laboratory, production and administrative facilities for Connaught
    48. 48. Diphtheria Toxoid: Taming ‘The Strangler’
    49. 49. Diphtheria Toxoid: Taming ‘The Strangler’ <ul><li>Eighty years ago, Canada led the world’s public health war against one of the most dreaded diseases ever known: diphtheria, a.k.a. “The Strangler.” </li></ul><ul><li>Despite the availability of Diphtheria Antitoxin, this disease remained a major childhood threat. </li></ul><ul><li>It is caused by the diphtheria bacteria, which releases a powerful toxin in the body, producing a strangulating and deadly membrane in the throat if left untreated. </li></ul>
    50. 50. Diphtheria Toxoid: Taming ‘The Strangler’ <ul><li>The key to victory was diphtheria toxoid, discovered by Dr. Gaston Ramon at the Pasteur Institute in Paris in 1923-24. </li></ul><ul><li>Ramon's discovery involved treating diphtheria toxin with formalin, which destroyed its toxicity while preserving its ability to stimulate natural antitoxin production.  </li></ul><ul><li>A few months after Ramon's discovery, during a visit to the Pasteur Institute, Dr. J.G. FitzGerald was so impressed by the new toxoid that he immediately called Dr. Peter Moloney (bottom right) back at the Toronto Labs and asked him to immediately begin preparing the toxoid.    </li></ul>American Journal of Public Health (1926)
    51. 51. Diphtheria Toxoid: Taming ‘The Strangler’ <ul><li>Landmark Diphtheria Toxoid field trials took place in many Ontario cities, particularly Hamilton, Toronto, Brantford and the Windsor area. </li></ul>This pioneering Canadian public health effort represented the first statistical demonstration of the value of a non-living vaccine in preventing a specific disease. <ul><li>In Hamilton, diphtheria dropped from 747 cases and 32 deaths in 1922, to 5 cases and zero deaths by 1931. </li></ul>
    52. 52. Diphtheria Toxoid: Taming ‘The Strangler’ <ul><li>During the 1930s and 1940s, armed with this very effective new vaccine, provided freely through provincial health departments, Canada led the world in diphtheria control, especially when compared to the U.S. and Great Britain. </li></ul><ul><li>In the early 1940s, British billboards boldly asked: “If Canada can do it, why can’t we?&quot; </li></ul>
    53. 53. Pertussis: Preventing ‘Whooping Cough’
    54. 54. Pertussis: Preventing ‘Whooping Cough’ <ul><li>1906 - The infection-causing bacterium first isolated and cultured by Belgian bacteriologists Jules Bordet and Octave Gengou and named Bordetella pertussis after Bordet . </li></ul><ul><li>1906-12 - Inspired by Bordet’s work, crude Pertussis vaccines prepared with various strains and methods and used quite widely in several countries, but with no clinical evaluation </li></ul><ul><li>1916-25 – Thorvald Madsen of Copenhagen conducts first clinical studies to evaluate pertussis vaccine prepared with “fresh” Phase I strains collected from whooping cough patients, rather than stock strains </li></ul><ul><li>1926 - 31 – Inspired by Madsen’s results, Dr. L.W. Sauer prepared a fresh strain pertussis vaccine on a small scale in his Chicago lab and was able to test its preventive value, later claiming it provided “good immunity” in the 300 young children he vaccinated. </li></ul>
    55. 55. Pertussis: Preventing ‘Whooping Cough’ <ul><li>1931 - 32 - Encouraged by the work of Madsen and Sauer, Dr Nelles Silverthorne began important Canadian work with fresh pertussis strains at his Hospital for Sick Children clinic in Toronto (below). </li></ul><ul><li>Silverthorne was also a Senior Research Fellow at Connaught Laboratories </li></ul>Dr Nelles Silverthorne
    56. 56. Pertussis: Preventing ‘Whooping Cough’ <ul><li>1936 - 37 - With such encouraging results, Connaught's fresh strain Pertussis Vaccine was ready for national distribution through Canada's public health departments </li></ul><ul><li>Based on the fresh strains of B. pertussis , Silverthorne and his Connaught colleagues prepared a whole cell Pertussis Vaccine that was subjected to a series of field trials. </li></ul><ul><li>For example, a Scarborough trial involving 500 children strongly suggested the effectiveness of the vaccine </li></ul><ul><li>Two major challenges: </li></ul><ul><li>Making the vaccine on a large scale </li></ul><ul><li>Making sure young children get the vaccine </li></ul>
    57. 57. Pertussis: Preventing ‘Whooping Cough’ <ul><li>Connaught's fresh strain Pertussis Vaccine was originally produced by cultivating the bacterium on a solid Bordet nutrient medium, which was increasingly inefficient to work with and vulnerable to contamination </li></ul>Dr R.J. Wilson <ul><li>In 1939, Connaught's Dr. R.J. Wilson began experiments to develop a more efficient production method based on a fluid culture medium recently developed in the U.S. </li></ul>
    58. 58. Pertussis: Preventing ‘Whooping Cough’ Dr L.N. Farrell & Edith Taylor <ul><li>Working with Drs. Leone Farrell & Edith Taylor, Wilson modified the Hornibrook medium and successfully adapted it for large-scale Pertussis Vaccine production during the early 1940s </li></ul><ul><li>The most efficient method involved rocking the culture bottles in a special rocker machine. </li></ul><ul><li>A decade later Farrell applied this design to the production of poliovirus for the Salk vaccine. </li></ul>
    59. 59. DP: 1 st Pediatric Combination Vaccine <ul><li>The introduction of fresh strain Pertussis Vaccine created a new challenge -- an extra course of needles for children. </li></ul><ul><li>Beginning in 1941, combining Pertussis Vaccine with the well-established Diphtheria Toxoid provided children with protection against both killer diseases at the same time with no extra shots </li></ul>Connaught worked closely with provincial and local health departments to expedite the evaluation and delivery of new combined vaccine products
    60. 60. DPT: Foundation of Pediatric Combination Vaccines <ul><li>1946 - Building on the success of Tetanus Toxoid at the front and DP at home, after WWII, the Connaught research team of R.J. Wilson, P.J. Moloney and D.T. Fraser developed the triple antigen DPT </li></ul><ul><li>The expanding use of DP, followed be even wider use of DPT resulted in an acceleration in the decline of whooping cough incidence across Canada, and most dramatically in the death rate </li></ul>
    61. 61. Connaught & World War II: Penicillin: Making the Miracle Drug
    62. 62. Penicillin: Making the Miracle Drug <ul><li>1928 – Discovered by Dr. Alexander Fleming at St. Mary’s Hospital, London, UK </li></ul><ul><li>Fleming noticed inhibited bacterial growth on culture plates caused by something produced from air-borne moulds that had fallen on the plates </li></ul><ul><li>Fleming named the inhibitive material ‘penicillin’ after the type of mould, penicillum, that had contaminated his culture plates </li></ul><ul><li>By 1938, researchers at Oxford University led by Dr. H.W. Florey, had expanded on Fleming’s work and successfully developed methods for growing, extracting and purifying enough penicillin to demonstrate is value as an antibiotic drug. </li></ul>Dr. Alexander Fleming and one of his contaminated culture plates with Penicillin mould
    63. 63. Penicillin: Making the Miracle Drug <ul><li>1941-43 – After Dr. H.W. Florey visited Canada and the U.S., researchers at the University of Toronto developed methods by which penicillin could be extracted from a crude broth on a small scale and prepared into a form suitable for clinical use </li></ul><ul><li>A pilot plant was needed to develop penicillin production on a larger scale </li></ul><ul><li>Aug 1943 – Canadian government asked Connaught to expedite large-scale production of penicillin to meet the needs of the Armed Services </li></ul><ul><li>Finding a suitable facility was a challenge, but fortunately a large and vacant building – the former Knox College – was available in Spadina Circle next to the main U of T Campus, but extensive renovations were needed </li></ul>
    64. 64. Penicillin: Making the Miracle Drug <ul><li>April 1944 – After extensive renovations, penicillin production began in what became officially known as Connaught’s “Spadina Division” </li></ul><ul><li>Soon after the new facilities were opened, a more efficient production method was developed based on growing the mould on the surface of a suitable medium in quart-sized milk bottles, rather than on open trays. </li></ul><ul><li>Adapting to the new method required re-planning to accommodate the incubation and processing of more than 250,000 bottles of culture weekly. </li></ul>
    65. 65. Penicillin: Making the Miracle Drug <ul><li>Nov 1945 – A significantly more efficient “Submerged Culture” penicillin production method was introduced at Connaught, although there were challenges acquiring the glass-lined steel tanks and other specialized equipment that were required </li></ul><ul><li>Also critical to the new production method was the development by Dr. L.N. Farrell of a mould strain capable of penicillin production yields that were many times higher than those from other available cultures </li></ul>
    66. 66. Other WWII Efforts: Influenza Vaccine <ul><li>1933 - Influenza virus types A and B (with various sub-strains) first isolated and adapted to grow in embryonated chicken eggs </li></ul><ul><li>First experimental influenza vaccines based on infected mouse lung, then chick embryo tissues and chorio-allantoic membrane; allantoic fluid was found to be best for cultivating influenza virus </li></ul><ul><li>Before the war, Connaught established a centre for the isolation of influenza viruses </li></ul><ul><li>1943 - Canadian Armed Forces asked Connaught to supply Influenza Vaccine (types A and B) </li></ul><ul><li>Aug 1944 - March 1945 - Connaught processed 2,000 eggs daily and prepared close to 30,000 doses of influenza vaccine per month </li></ul>
    67. 67. Conquering The Crippler: Connaught & Polio Vaccines
    68. 68. Connaught & Polio Vaccines: Key Global & Canadian Research Foundations <ul><li>1908 – Poliovirus first isolated </li></ul><ul><li>1910 – First major polio epidemic year in Canada </li></ul><ul><li>1927-32 - Major polio epidemics begin in B.C. and then in turn strike Alberta, Manitoba, Ontario, Quebec </li></ul><ul><li>1928 – Connaught prepares polio convalescent serum from blood of recovered cases in hopes of minimizing paralysis in new cases </li></ul><ul><li>1937 – Ontario’s worst polio epidemic - 2,456 cases, 110 deaths (more than 4,000 cases across Canada) </li></ul><ul><li>1938 – National Foundation for Infantile Paralysis (March of Dimes) founded by US President F.D. Roosevelt </li></ul><ul><li>1939-43 – Connaught conducts epidemiological studies into non-paralytic poliovirus strains supported by NFIP grants </li></ul>
    69. 69. Connaught & Polio Vaccines: Key Global & Canadian Research Foundations <ul><li>1947 - Dr. A.J. Rhodes (right) launches a comprehensive research program at Connaught Laboratories to investigate the virology, epidemiology and clinical diagnosis of polio. </li></ul><ul><li>1949 - Hopes for a polio vaccine raised when a research team in Boston, led by Dr. J. Enders, discovered a way to grow poliovirus in a test tube using non-nervous tissues </li></ul>
    70. 70. 16 “ Medium 199”: The 1st Synthetic Media & Connaught’s Breakthrough Coincidence Morton Morgan Parker <ul><li>1949 - Connaught research team develops the first chemically defined “Medium 199,” originally for nutritional studies of cancer cells using tissue cultures </li></ul><ul><li>“ Medium 199” a precise mixture of more than 60 ingredients </li></ul>
    71. 71. Dr Arthur E. Franklin “ Medium 199” The Key to Poliovirus Growth <ul><li>1950-51 - Using Ender’s methods, Rhodes was growing poliovirus in test tubes, but reliant on traditional animal-based tissue culture sera </li></ul><ul><li>1951 - Through his friendship with one of the “Medium 199” discoverers (Morgan), a member of Rhodes’ research team, Dr. A.E. Franklin, tried the new synthetic medium for cultivating poliovirus in tissue cultures </li></ul><ul><li>The use of this medium vastly improved the yields and purity of poliovirus cultures. </li></ul>
    72. 72. Dr. Jonas E. Salk: Vaccine Pioneer @ University of Pittsburgh <ul><li>In the meantime, by 1951, Dr. Jonas Salk had shown that an inactivated poliovirus vaccine could prevent polio in monkeys </li></ul><ul><li>News of Connaught’s serum-free “Medium 199” and its successful use by Rhodes’ team for poliovirus cultivation, opened the door for Salk to develop and test an inactivated poliovirus vaccine that was safe for use in use in human children </li></ul><ul><li>However, Salk could only make his vaccine on a small scale </li></ul>
    73. 73. “ The Toronto Method” Facilitating Large Scale Poliovirus Production <ul><li>1952 - Recognizing Connaught’s experience in developing large scale vaccine and biologicals production technologies (ie. insulin, diphtheria toxoid, penicillin), the NFIP financed a major pilot project at the Toronto Labs to cultivate poliovirus in large quantities </li></ul><ul><li>1953 - Building on her experience with ‘deep culture’ pertussis and other vaccines, Dr. Leone N. Farrell successfully developed a method to mass produce poliovirus using Medium 199 in large Povitsky bottles incubated on special rocking machines </li></ul>Dr L.N. Farrell and prototype “ Toronto Method” bottle rocking machine, 1953
    74. 74. Salk Polio Vaccine Field Trial: Connaught Supplies Poliovirus Fluids <ul><li>July 1953 - In the wake of the worst polio epidemic year in U.S. history (and the start of Canada’s worst), and encouraged by Salk’s progress and Connaught’s “Toronto Method,” the NFIP asked the Labs to provide all of the poliovirus fluids required to conduct an unprecedented national field trial of Salk’s inactivated polio vaccine. </li></ul><ul><li>1953-54 - Connaught produced over 3,000 litres of poliovirus fluids for the U.S. trial </li></ul><ul><li>Large bottles of poliovirus fluids were shipped to U.S. by station wagon to Park Davis in Detroit and Eli Lilly in Indianapolis for inactivation and processing into the finished vaccine </li></ul><ul><li>1954-55 - Connaught then focused on full preparation of vaccine for eventual Canadian use </li></ul>
    75. 75. April 24, 1954: Launch of Salk Vaccine Field trial <ul><li>1,800,000 children enrolled across U.S; in May Alberta, Manitoba and Halifax joined trial, along with parts of Finland </li></ul><ul><li>For triple-blind field trial, children received either the vaccine, a placebo of Medium 199, or were observed </li></ul>
    76. 76. April 12, 1955: “V-Day” Salk Vaccine Trial Results Announced <ul><li>April 12, 1955 – Unprecedented media attention to announcement of field trial results in Ann Arbor, Michigan </li></ul><ul><li>Salk vaccine 60-90% effective against the three types of poliovirus </li></ul><ul><li>Vaccine immediately licensed in U.S. and Canada </li></ul><ul><li>In Canada, Salk vaccine distributed through federal-provincial free program for children and subjected to further study of its effectiveness </li></ul><ul><li>Canadian distribution of Connaught’s Salk vaccine continued without interruption despite suspension of U.S. immunizations after 79 polio cases linked to incompletely inactivated vaccine lots produced by Cutter Laboratories in California. </li></ul>
    77. 77. Connaught Provides Salk Vaccine to the World <ul><li>Soon, Connaught was exporting Salk vaccine to some 44 other countries that were without protection against polio’s growing global threat </li></ul><ul><li>1957 - Once able to meet Canadian requirements, Connaught began to export Salk vaccine, first to Czechoslovakia and then to Great Britain, which were otherwise without polio protection </li></ul>
    78. 78. <ul><li>1959 – Building on the DP and DPT models designed to minimize injections, Connaught pioneered a new generation of combined vaccines that include Salk polio vaccine -- DPT-Polio, DT-Polio, T-Polio </li></ul><ul><li>1955-62 - Canadian polio incidence falls dramatically, although not without some significant polio outbreaks where immunization rates among adults and young children were low </li></ul>DPT-Polio: The Key to Polio Control in Canada
    79. 79. Connaught & Polio Vaccines: Leadership in Oral Polio Vaccine Development <ul><li>1959 - Seed pools were provided by Dr Albert B. Sabin of the University of Cincinnati </li></ul><ul><li>1960-61 - OPV “Field Demonstrations” were conducted in Nova Scotia, Quebec and Saskatchewan </li></ul><ul><li>1961 - 24,000 were immunized with Connaught’s trivalent OPV in Prince Albert, Saskatchewan </li></ul><ul><li>March 1962 – Connaught’s trivalent Sabin Oral Polio Vaccine licensed in Canada </li></ul><ul><li>May 1962 - Almost the entire population of Saskatchewan (over 700,000) received OPV during a month-long “demonstration” in May 1962 </li></ul>
    80. 80. Connaught Provides Sabin Vaccine to the World <ul><li>1961 - Connaught supplies 3 million doses of OPV to Japan to bring a major polio epidemic under control </li></ul><ul><li>Connaught soon exports OPV to many other countries, becoming a world leader in the battle against polio around the world </li></ul>
    81. 81. Connaught & Polio Vaccines: Advances in Polio Vaccine Production <ul><li>1965 – Purified concentrated IPV </li></ul><ul><li>1975 – Multi-surface Cell Propagator (below) developed at Connaught -- 1 MSCP unit replaced about 50 large Povitsky bottles </li></ul><ul><li>Late 1970s - Connaught began to experiment with Human Diploid Cell lines to replace monkey kidney cells in polio vaccine production </li></ul><ul><li>1980s - development of a enhanced IPV using the MRC-5 cell line and micro-bead fermentor technology was undertaken </li></ul>
    82. 82. Influenza: Facing a Pandemic (Part II)
    83. 83. <ul><li>Late 1956 – WHO network of Influenza Centres tracked the spread of an epidemic from eastern Asia to Europe and North America, this worrisome situation caused by a new influenza strain known as A/Asia/57 (or H2N2) </li></ul><ul><li>Spring 1957 – UK, Australian and U.S. Labs start preparing new influenza vaccine, but supplies limited </li></ul><ul><li>July 1957 – Federal & provincial governments ask Connaught to expedite preparation of A/Asia/57 vaccine for Canada </li></ul><ul><li>Aug 1957 – Production begins at Connaught after several production and processing methods investigated </li></ul>Avian Influenza: Pandemic Preparations, 1957-58
    84. 84. <ul><li>Early Oct 1957 – With production at 10,000 doses per week, Connaught delivers 400,000 doses of influenza vaccine, which were distributed to all provinces by end of November </li></ul><ul><li>While influenza incidence was declining, there were concerns that a second pandemic wave possible, as had occurred in 1918-19 </li></ul>Avian Influenza: Pandemic Preparations, 1957-58 <ul><li>Jan 1958 – After Dominion Council of Health recommended a vaccine stockpile Connaught prepared an additional 1 million doses that were kept in bulk </li></ul>
    85. 85. Slaying the Speckled Monster: Connaught & Smallpox Eradication
    86. 86. Making “The Best Smallpox Vaccine in this Galaxy” Connaught and Smallpox Vaccine Improvements <ul><li>1957-58 - Major smallpox epidemic strikes Bangladesh, causing 100,000 cases. Red Cross and WHO seek emergency supplies of vaccine </li></ul><ul><li>1958 - Connaught quickly supplies 1.5 million doses of liquid vaccine, but emergency prompts intense work to develop a freeze-dried smallpox vaccine </li></ul><ul><li>1959-62 – Dried smallpox vaccine prepared on a small scale and subjected to field trials with Canadian military </li></ul><ul><li>1962 – North American smallpox scare sparked by 14-year-old Canadian boy (right), who returned home from Brazil via New York with mild smallpox case, intensifies interest in smallpox eradication and expedited work on dried smallpox vaccine at Connaught </li></ul>
    87. 87. Making “The Best Smallpox Vaccine in this Galaxy” Connaught and Smallpox Vaccine Improvements <ul><li>1962 – Dr. Paul Fenje (left) assumes responsibility for Connaught’s expanded and higher priority smallpox vaccine research, development and production program, especially freeze-dried vaccine </li></ul><ul><li>1965-66 – Connaught’s dried smallpox vaccine meets heightened WHO and U.S. standards </li></ul><ul><li>1966 – New smallpox vaccine production facility at Connaught enables expanded production for Canadian and global markets </li></ul>
    88. 88. <ul><li>1967-68 – Drs. Paul Fenje and R.J. Wilson of Connaught begin consulting work in South America to improve the quality of local smallpox vaccine producers. </li></ul>Connaught Toronto <ul><li>1967 – Connaught: named one of two WHO International Smallpox Vaccine Reference Centers. Connaught focuses on Western Hemisphere (esp. Latin American) </li></ul>RIJKS Bilthoven Connaught and Global Smallpox Eradication, 1967-79 <ul><li>1967 – WHO launch global smallpox eradication program </li></ul>
    89. 89. Using “The Best Smallpox Vaccine in this Galaxy” Connaught and Smallpox Eradication <ul><li>1970-74 – Canadian government donates a total of 35,000,000 doses of Connaught’s freeze-dried smallpox vaccine to the WHO </li></ul><ul><li>April 1972 – Major smallpox outbreak in Bangladesh prompts emergency and expedites delivery of 5 million doses of Connaught’s dried vaccine to be used with the bifurcated needle </li></ul>&quot;Paul Fenje has recently been asking me whether there have been any reports from the field on his ‘best smallpox vaccine in this galaxy.’ I think he is rather anxious to know how it is performing although I have few doubts that if properly applied it will do what is expected of it.” R.J. Wilson to D.A. Henderson (Director, WHO Smallpox Eradication Program), Aug 10, 1971
    90. 90. Using “The Best Smallpox Vaccine in this Galaxy” Connaught and Smallpox Eradication <ul><li>Oct 1977 – Last natural case of smallpox in the world recorded in Somalia </li></ul><ul><li>Early 1979 – Fenje prepares 17 vaccinia pulps for proposed WHO smallpox vaccine stockpile </li></ul><ul><li>Dec 1979 – Smallpox officially declared eradicated from the globe </li></ul><ul><li>July 1980 – Connaught’s smallpox production plant closes and remaining vaccinia pulps and related materials kept in deep freeze </li></ul>“ It surely will not be a great problem to keep the seed virus and pulps for some time to come and at least in this way we might have something to fall back on so as to be able to prepare our licensed product. ” Dr. E.W. Pearson, Medical Director, Connaught, Sept. 12, 1980
    91. 91. 2001-2003 - History Repeats Itself: Meeting the New Smallpox Bio-terrorism Threat <ul><li>Sept 11, 2001 – Fear of Smallpox returns after U.S. terrorist attacks </li></ul><ul><li>2002 - 17 vaccinia pulp lots resurrected after 22 years in deep freeze storage </li></ul><ul><li>2003 – After careful analysis of original production and quality control measures used in the preparation of the vaccinia pulps, followed by extensive testing, most of the pulps are utilized to prepare a new Canadian smallpox vaccine stockpile </li></ul>
    92. 92. “ Too Big For Canada, Too Small for the World” Connaught’s Privatization & Global Partnerships, 1972-1989
    93. 93. Connaught For Sale: Privatization & Transformation <ul><li>Late 1960s – “Winds of change” blowing through University of Toronto driven by enormous expansion and transformation of University to meet demands of “baby boomers” </li></ul><ul><li>Connaught increasingly regarded as a valuable asset to assist in the development of U of T and suggestions were made to move some portion of its profits to the parent </li></ul><ul><li>Main reasons to sell Connaught – growing complaints from competing pharmaceutical firms about non-taxable status within U. of T; growing regulatory demands on biologicals production; increasing legal liabilities; declining margins on main biological products; limited ability and desire of U of T administration to use educational funds to make the necessary investments to modernize Connaught’s buildings and facilities and to expand its exports </li></ul>
    94. 94. Connaught For Sale: Privatization & Transformation <ul><li>1972 – Canadian Development Corporation (CDC) offers $25 million to purchase Connaught from the University of Toronto </li></ul><ul><li>CDC - Created in 1971 by the Government of Canada as a crown corporation “to help develop and maintain strong Canadian controlled and managed corporations in the private sector of the economy and to give Canadians greater opportunities to invest and participate in the economic development of Canada.” </li></ul><ul><li>With an initial investment of $312 million, the CDC would soon own companies involved in petroleum, mining, natural resources, venture capital and health care </li></ul><ul><li>June 30, 1972 – Connaught is CDC’s first acquisition, beginning a significant transformation process that started with a new name: Connaught Laboratories Limited </li></ul>
    95. 95. Connaught Laboratories Limited: Consolidations & Expansions <ul><li>1972 – 1979 – Challenging period for Connaught, marked by reduction of staff from about 900 and sales of $15 million, to less than 750 people and sales of more than $75 million, and from loosing money to making its first profit </li></ul><ul><li>Major focus of Connaught on improved productivity and long-term strategic planning through modernized technology and more professional management </li></ul><ul><li>July 1980 – Connaught Research Institute established to reinforce links between Connaught and academic scientific community, which had declined after CDC sale </li></ul>
    96. 96. Connaught Laboratories Incorporated: U.S. Expansion in Swiftwater, PA <ul><li>1896 – Pocono Laboratories established by Dr. Richard Slee to prepare smallpox vaccine </li></ul><ul><li>1930 – National Drug Co. purchased Pocono Labs </li></ul><ul><li>1977 – Swiftwater Labs facility donated to Salk Institute for Biological Studies when Merrill-National Labs withdraws from vaccine business </li></ul>Dr Richard Slee (left), Swiftwater site sign, 1930s, and Dr. Jonas Salk with President of Richarson-Merrill Inc in 1977 (which had adsorbed National Drug in 1961) discussing Swiftwater’s future
    97. 97. Connaught Laboratories Incorporated: U.S. Expansion in Swiftwater, PA <ul><li>1975 – 1977 – Dr. Jonas Salk publicly expresses growing concerns about lack of vaccine choice in U.S., especially since OPV universally used despite its risk of causing polio, and growing legal challenges, while IPV only available via import from Connaught in Canada </li></ul><ul><li>Jan 1, 1978 – Based on Salk’s close relationship with Connaught, a desire to retain vaccine production capacity in the U.S. while providing Connaught with a U.S. outlet for its IPV and other products, Connaught purchases the 50-acre Swiftwater Laboratories facility from the Salk Institute for $1.99 million to establish Connaught Laboratories Incorporated </li></ul>
    98. 98. Connaught’s Canadian & International Partnerships, 1980s <ul><li>In addition to the creation of the Connaught Laboratories Inc. U.S. subsidiary in Swiftwater in 1978 and the establishment of Connaught-Novo joint venture in 1984 for insulin production, Connaught entered into several other significant Canadian and international alliances during the early1980s: </li></ul><ul><li>Bioresources - (Halifax, NS, based blood plasma collection firm) </li></ul><ul><li>Dominion Biologicals - (Truro, NS, blood serum, typing company) </li></ul><ul><li>Integrated Genetics (Boston, MA, firm developing a hepatitis B vaccine in the U.S.) </li></ul><ul><li>E.R. Squibb & Sons - U.S. marketing agreement creates Connaught/Squibb Inc. </li></ul><ul><li>Japanese company developing an acellular pertussis vaccine </li></ul>
    99. 99. Connaught’s Shifting Ownership: The Road to France <ul><li>1984 - Canadian Development Corporation (CDC) sold 34% of its shares to the public </li></ul><ul><li>1985 - Canadian government privatized Connaught Laboratories, creating a holding company later called Connaught Biosciences Incorporated (CBI) </li></ul><ul><li>1986 - Director-General of Institut Merieux makes first of many visits to Connaught </li></ul><ul><li>1986-87 - CDC unsuccessfully approached U.S. investors when Canadian buyers proved unwilling to invest in Connaught </li></ul><ul><li>1987 - CDC divested itself completely of remaining 25% of its Connaught shares; 1/2 going to Institut Merieux and 1/2 to Caisse de Depot et Placement du Quebec </li></ul>
    100. 100. Connaught’s Shifting Ownership: The Road to France <ul><li>1988 - After two years of unsuccessful merger discussions, Institut Merieux launched a “hostile takeover attempt” for another 20% of CBI shares, but was blocked by the Toronto and Montreal Stock Exchanges; other potential partnerships explored </li></ul><ul><li>1989 - Renewed merger negotiations with Merieux successful, for a final purchase price of $943.5 million </li></ul>Merieux’s offer subjected to intense review by Investment Canada and the Canadian media and despite some controversy, the deal was accepted
    101. 101. Connaught’s Shifting Ownership: The Road to France <ul><li>1897 - Institut Merieux (IM) created in Lyon, France, by Marcel Merieux, who had worked with Louis Pasteur </li></ul><ul><li>1968 - Rhone-Poulenc (RP) acquires 51% of IM capital </li></ul><ul><li>1974 - Pasteur Institute establishes Pasteur Production focused on vaccine production </li></ul><ul><li>1985 - Pasteur Production acquired by IM to create Pasteur Vaccines </li></ul><ul><li>1989 - IM acquires Connaught in Canada and US </li></ul><ul><li>1990 - Pasteur Merieux Serums & Vaccines (PMsv) created </li></ul><ul><li>1996 - Pasteur Merieux Connaught new name of PMsv </li></ul>
    102. 102. Building the Best Vaccine Combinations
    103. 103. <ul><li>1988 - ProHibit launched, providing protection against Haemophilus influenzae b (or Hib) - the leading cause meningitis in infants and children </li></ul><ul><li>1992 - 93 - Connaught integrated the conjugate Hib vaccine with its line of pertussis vaccine combinations, such as Act-Hib+DPT Adsorbed </li></ul>These combination vaccines led to high immunization rates and a dramatic decline in disease, particularly Hib . New Progress in Combination Vaccines: Haemophilus influenza b (Hib) Products
    104. 104. Connaught’s PENTA Team PENTA Launch, with Jonas Salk (right) participating remotely <ul><li>The World’s first modern 5-component vaccine, combining whole cell Pertussis with Diphtheria, Tetanus, IPV and Hib vaccines. </li></ul>New Progress in Combination Vaccines: PENTA, 1994
    105. 105. 5-Component Acellular Pertussis Vaccine Creating the Gold Standard in Canada <ul><li>1980s – Connaught team of scientists started the quest to develop an acellular pertussis vaccine for infants. </li></ul><ul><li>1970s-80s - Persistent concerns about the effectiveness and safety of whole cell pertussis vaccine prompts research to develop a new acellular type of vaccine </li></ul><ul><li>1990 – Connaught’s Acellular Pertussis Vaccine was ready for clinical trial in Sweden, where there was no immunization program and a high rate of infection with which to test efficacy </li></ul><ul><li>1996 - Following several years of preparation by Connaught’s regulatory team, Connaught's 5-component Acellular Pertussis vaccine was licensed in Canada. </li></ul>
    106. 106. Pentacel quickly becomes universally used across Canada, effectively enabling the replacement of OPV with IPV in all provinces without extra needles New Progress in Combination Vaccines: Pentacel, 1997 <ul><li>1997 - Pentacel launched in Canada: pioneering new pediatric combination vaccine containing: </li></ul><ul><ul><li>5-component acellular pertussis </li></ul></ul><ul><ul><li>Diphtheria </li></ul></ul><ul><ul><li>Tetanus </li></ul></ul><ul><ul><li>IPV </li></ul></ul><ul><ul><li>Hib </li></ul></ul><ul><li>Research, development & manufacturing of Pentacel entirely Canadian </li></ul>
    107. 107. Increase in adolescent pertussis with decrease in infant pertussis New Challenges: Adolescent and Adult Pertussis Adolescent and adult pertussis began to increase in the 1990s in Canada just as incidence in infants and children was coming down due to the 5-component combination vaccine distributed in Pentacel. The need for an adolescent and adult pertussis vaccine led to the development of Adacel
    108. 108. <ul><li>The world’s first vaccine for adolescents and adults containing 5-component acellular Pertussis Vaccine in combination with booster doses of Diphtheria and Tetanus Toxoids. </li></ul>New Progress in Combination Vaccines: Adacel, 1999 Adacel indirectly protects infants under 6 months who have not had their primary series of pertussis immunizations by preventing pertussis in adolescent or adult family members and contacts, thus providing a protective “ cocoon” around the infant.
    109. 109. 5-Component Pertussis Combinations <ul><li>Pentacel </li></ul><ul><li>Pediacel (fully liquid form of Pentacel) </li></ul><ul><li>Quadracel </li></ul><ul><li>Daptacel </li></ul><ul><li>Adacel </li></ul><ul><li>Repavax (Adacel-IPV) </li></ul><ul><li>1999 to present: More than 30 million doses of combination products containing 5-component acellular pertussis vaccine produced in Canada have been distributed globally </li></ul>
    110. 110. From Aventis Pasteur to Sanofi Pasteur: Maintaining Connaught’s Canadian Identity into the 21 st Century
    111. 111. Canada & Global Biotech Partnerships: Connaught & the Creation of Aventis Pasteur <ul><li>Rhone-Poulenc </li></ul><ul><li>1928 - French chemical and pharmaceutical company founded after merger of Société Chemique des Usines du Rhône and Établissements Poilenc Frères </li></ul><ul><li>1994 - Pasteur Mérieux Serums & Vaccines wholly owned subsidiary </li></ul><ul><li>1863 - German life science company founded as Teerfarbenfabrik Meister, Lucius & Co. in Hoechst, near Frankfurt </li></ul><ul><li>1951 - Hoeschst AG re-founded in 1951 </li></ul><ul><li>1987 - U.S. subsidiary, Hoechst-Celanese established </li></ul><ul><li>Dec 1999 - Rhône-Poulenc and Hoechst unite their Life Sciences activities into a single company known as Aventis , based in Strasbourg, France </li></ul><ul><li>Pasteur Merieux Connaught in Canada becomes Aventis Pasteur Limited (Connaught Campus) </li></ul>
    112. 112. Canada & Global Biotech Partnerships: Connaught & the Creation of sanofi pasteur <ul><li>Sanofi: </li></ul><ul><li>1973 - founded by Elf Aquitaine (a French oil company) when it took control of the Labaz Group (a pharmaceutical company) </li></ul><ul><li>1994 - first significant expansion into U.S. market </li></ul><ul><li>Synthelabo: </li></ul><ul><li>1970 - founded through merger of two French pharmaceutical labs ( Laboratoires Dausse (est 1834)) & Laboratoires Robert & Carriere (est 1899)) </li></ul><ul><li>1993 - first expansion into U.S. market </li></ul><ul><li>1999 - Creation of Sanofi Synthelabo, based in Paris, a major goal of the merger was to accelerate expansion into U.S. market </li></ul><ul><li>1999 - Aventis created through merger of Rhone Poulenc & Hoechst </li></ul><ul><li>Early 2004 - Sanofi Synthelabo launches €47.8 billion hostile take-over of Aventis and is rejected </li></ul><ul><li>Fall 2004 - With French government intervention, new friendly offer of €54.5 billion is accepted leading to creation of Sanofi-Aventis </li></ul><ul><li>2005 – Aventis Pasteur globally becomes sanofi pasteur , with main Canadian site officially named Sanofi Pasteur Limited (Connaught Campus) </li></ul>
    113. 113. Sanofi Pasteur: The Broadest Range of Vaccines Worldwide Bacterial diseases Pertussis Diphtheria Haemophilus influenzae b Meningococcal meningitis Pneumococcal infections Tetanus Tuberculosis Typhoid fever Cholera Viral diseases Yellow fever Mumps Poliomyelitis Measles Rubella Influenza Hepatitis A Hepatitis B Rabies Japanese encephalitis Chickenpox Manufactures vaccines against 20 diseases <ul><li>400 Brands </li></ul><ul><li>More than 1.6 billion doses sold to protect more than 500 million people in 150 countries around the world </li></ul>Made in Canada
    114. 114. Connaught Campus Recent Investments <ul><li>Warehouse (2000) $15 M </li></ul><ul><li>Component Pertussis (5cP) (2003) $16 M </li></ul><ul><li>Quality Operations (2003) $26 M </li></ul><ul><li>Cancer Development (2004) $22 M </li></ul><ul><li>Site Perimeter (2005) $2 M </li></ul><ul><li>Component Pertussis (5cP) (2007) $15M </li></ul><ul><li>IPV Expansion (2007) $25M </li></ul><ul><li>Testing Facility (2007) $16M </li></ul><ul><li>Washing/Sterilizing/Lab Upgrade (2007) $13M </li></ul><ul><li>Clean Steam Upgrade (2007) $2M </li></ul><ul><li>Go-generation & High Voltage Distribution System Upgrade (2007) $12M </li></ul><ul><li>Admin. Building Renovations (2007) $2M </li></ul><ul><li>Water Pre-treatment System Upgrade $6M </li></ul><ul><li>Historical Centre (2008) $3 M </li></ul><ul><li>Component Pertussis (5cP) (2008) $6M </li></ul><ul><li>Filling & Packaging Upgrade (2009) $3M </li></ul><ul><li>cGMP Upgrades (2009) $13M </li></ul><ul><li>R&D (2009) $101M </li></ul>
    115. 115. Showcasing a Unique Heritage Barton Avenue Stable - 1913 - 2001
    116. 116. Showcasing a Unique Heritage 2004
    117. 117. Showcasing a Unique Heritage Heritage Centre 2004 - 2010
    118. 118. Sources & Resources <ul><li>Archives, Sanofi Pasteur Limited (Connaught Campus), Toronto </li></ul><ul><li>Health Heritage Research Services - http://healthheritageresearch.com </li></ul><ul><li>C.J. Rutty & S. Sullivan, This Is Public Health: A Canadian History (Canadian Public Health Association, 2010) - http://cpha100.ca </li></ul><ul><li>Sanofi Pasteur in Canada - http://sanofipasteur.ca </li></ul>Primary Research & Images: Further Information on the History of Connaught & Public Health in Canada:
    119. 119. Acknowledgements <ul><li>This presentation is based on academic and professional research on the history of Connaught Laboratories and related topics conducted with support from: </li></ul><ul><li>Luis Barreto - VP, Immunization Policy & Scientific Affairs, Sanofi Pasteur Limited </li></ul><ul><li>Rob Van Exan - Director, Immunization Policy, Sanofi Pasteur Limited </li></ul><ul><li>Hugh McNaught - Manager, Library Services, Sanofi Pasteur Limited </li></ul><ul><li>Nancy Simpson - Manager, Communications, Sanofi Pasteur Limited </li></ul><ul><li>J. Mark Lievonen - President, Sanofi Pasteur Limited </li></ul>

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