Chasing Influenza

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Influenza presents an ever-changing target to those who would study or control it. Unlike other infectious diseases, where a single dose of vaccine (or single series of doses) confers long-term protection, flu vaccination is an annual affair. This is because the influenza virus is constantly changing its surface proteins (called antigens), which makes detection by the human immune system more difficult. Most of these mutations are minor, and a bout of influenza is not a serious matter for the majority of the population. However, occasionally the virus changes dramatically, making influenza a killer that can evolve quickly into a pandemic.

Antigenic Drift: How the Influenza Virus Adapts from Vaccine Makers Project on Vimeo.

In the United States, vaccination is recommended for each annual “flu season,” and every year the vaccine is reformulated based on the particular influenza virus strains currently in circulation. Beginning in the 1950s, the World Health Organization has overseen a global network of agencies that work continuously to monitor the virus. Scientists and public health officials use the best information available to determine the most effective constituents of the vaccine.

This intense focus on influenza can be traced back to the worst pandemic in human history – the “Spanish influenza” that struck in 1918 in the midst of the First World War. This episode, with its estimated death toll of 50 million, continues to haunt our consciousness of this disease. Pandemics – and the threat of these episodes – have spurred ongoing investigations of influenza, resulting in a vast body of knowledge that informs the fields of bacteriology, virology, and epidemiology.

 

The museum’s collections provide evidence of this history and our attempts to understand and control this disease.

Grippe Knockers, Vick’s Family Remedies Company, ca 1908-1918.

Grippe Knockers, Vick’s Family Remedies Company, ca 1908-1918. Named for LaGrippe, the French term for influenza, Grippe Knockers contained acetanilide, a popular fever and pain reducer first marketed in the 1880s. Analgesics (for aches and pain) and antipyretics (for fever) continue to be popular treatments for bouts of the flu.

Bacterial vaccines from the 1930s.

Bacterial vaccines from the 1930s.Catarrhalis Immunogen (Combined) Parke, Davis & Co. and Sherman’s Influenza Vaccine. Although influenza is a viral disease, secondary bacterial infections such as pneumonia, are often responsible for fatalities.

The influenza pandemic of 1918 decimated populations around the world. America’s most promising bacteriologists and research institutions raced to try to identify the pathogen responsible for this devastating outbreak. The most likely culprit was the “influenza bacillus” – also known as “Pfeiffer’s bacillus,” after the German bacteriologist Richard Pfeiffer who first isolated it in flu patients in 1892.

But while researchers often found the bacillus in flu victims, it was not always present. A range of other bacterial pathogens were also isolated from patients including pneumococcus, streptococcus, staphylococcus, and micrococcus catarrhalis. In response to these discoveries, manufacturers developed bacterial vaccines – essentially a mixture of these microorganisms that would provoke an immune response and hopefully fend off the infection.

A New York City typist wears a mask to protect herself during the 1918 flu pandemic. Courtesy National Archives and Records Administration, record number 165-WW-269B-16.

A New York City typist wears a mask to protect herself during the 1918 flu pandemic. Courtesy National Archives and Records Administration, record number 165-WW-269B-16.

In the decades following the pandemic, pharmaceutical companies sought to improve on these products. Bacterial “immunogens” represented an attempt to separate the antigenic substances which stimulate immunity from the whole bacteria cell. In other words, the immunogen was a purer form of the vaccine, free of extraneous bacterial proteins and toxins that sometimes caused unwanted reactions.

In the 1930’s researchers succeeded in isolating the influenza virus, first from pigs who are also susceptible to influenza, and shortly after from humans. Proof that influenza was a viral disease finally put to rest older theories about the bacterial origin of the disease. Scientists also developed new methods for growing viruses (in fertilized chicken eggs)– a critical achievement for the field of virology and vaccine development.

Three examples of early Influenza Virus Vaccine, Types A and B, 1945-1952, made by Lederle Laboratories, Parke, Davis and Co., and E. R. Squibb & Sons.

Three examples of early Influenza Virus Vaccine, Types A and B, 1945-1952, made by Lederle Laboratories, Parke, Davis and Co., and E. R. Squibb & Sons. The label on the 1945 Parke Davis vaccine (middle) reads: “Prepared in the extra-embryonic fluid of the chick embryo and formalin-killed.”

In 1941, determined to avoid another wartime pandemic, the US Army established the Commission on Influenza and Vaccine Development. Within two years, the commission developed a vaccine ready for testing. The vaccine included the two main viral strains – Type A and Type B – known to be responsible for human influenza. Scientists had recently discovered a variant of the type A virus, and this too was included in the new vaccine. In hindsight, this may have been an early warning that this shape-shifting virus was not to be conquered easily. In 1945, the Army vaccinated eight million men and, in the following year, the vaccine was available for the general public.

Influenza Vaccine, Monovalent Type A

Influenza Vaccine, Monovalent Type A made by the National Drug Company of Philadelphia, PA, 1958-59. This vaccine was formulated specifically to combat the Type A “Asian strain,” which resulted in about 70,000 deaths in the US as part of the Asian Flu pandemic of 1957-58, the first flu pandemic since 1918.

The Asian Flu pandemic of 1957-58 was the first pandemic to emerge after the introduction of the virus vaccine. The episode provided a test case of how government, medical scientists, and vaccine manufacturers would respond to a pandemic threat. News reports of the epidemic in Hong Kong appeared in mid-April 1957; virologist Maurice Hilleman at the Army’s Walter Reed Medical Center acted quickly to procure a specimen of the virus by May; and by mid-August a monovalent Type A vaccine of the new “Asian strain” was ready for testing. The speed of response was commendable, although it was not fast enough to supply vaccine to all who would need it. For those who did get vaccinated, studies showed that the vaccine had reduced incidence of the infection by one-half to two-thirds.

Influenza vaccine, Monovalent, Type A, Merrell-National Laboratories. Hsw1Nsw1 is the designation on the label for this H1N1 swine flu variant virus that emerged in New Jersey in 1976.

Influenza virus vaccine, Monovalent, Type A, Merrell-National Laboratories. Hsw1Nsw1 is the designation on the label for this H1N1 swine flu variant virus that emerged in New Jersey in 1976.

The swine flu episode of the mid-1970s provides a counterpoint to the Asian pandemic. In 1976, an influenza outbreak at an army base in Fort Dix, New Jersey, caused the death of a young private. Subsequent testing revealed the presence of a swine flu type virus (H1N1) in the victim – the same type associated with the 1918 pandemic. To avoid a potential repeat of the 1918 disaster, public health and government leaders pursued an aggressive vaccination campaign. Their reasoning was summed up thus: “Better a vaccine and no epidemic, than an epidemic with no vaccine.”

Poster for the Swine Flu vaccination campaign urging US citizens to get vaccinated. U.S. Public Health Service, Center for Disease Control, 1976.

Poster for the Swine Flu vaccination campaign urging US citizens to get vaccinated. U.S. Public Health Service, Center for Disease Control, 1976.

About 40 million Americans were vaccinated before the swine flu campaign was terminated. As it turned out, the virus failed to spread beyond Fort Dix, precluding a feared global pandemic. The episode is largely considered a public health fiasco and has continued to be studied for the insights it offers into the multiple factors that drive decision-making.

The 1976 episode introduced many Americans to “swine flu” and the particular dangers of an influenza strain that moves between species. In spring 2009, swine flu recaptured the headlines when a variant virus emerged in Mexico, and with it, the threat of pandemic and debate about the best response.

Influenza A (H1N1) 2009 Monovalent Vaccine made by CSL Limited, Parkville, Australia.

Influenza A (H1N1) 2009 Monovalent Vaccine made by CSL Limited, Parkville, Australia.

Pandemic situations raise concerns about our capacity to quickly manufacture effective and safe vaccines. They also raise concerns about access: How will the vaccines be distributed to those in need? Who will get it first? Who will make and enforce those decisions?

Currently not on view
Location
Currently not on view
date made
ca 1977
product expiration date (Influenza virus vaccine)
1977-08-01
maker
Richardson-Merrell, Inc
ID Number
2012.0165.825
catalog number
2012.0165.825
accession number
2012.0165
Currently not on view
Location
Currently not on view
date made
ca 1938
maker
Parke, Davis and Company
ID Number
MG.M-04673
accession number
147292
catalog number
M-04673
Currently not on view
Location
Currently not on view
date made
ca 1974
expiration date
1974-11-25
maker
Parke, Davis and Company
ID Number
1982.0043.006B
catalog number
1982.0043.006B
accession number
1982.0043
Currently not on view
Location
Currently not on view
date made
ca 1973
expiration date
1973-04-14
ID Number
1982.0043.030A
catalog number
1982.0043.030A
accession number
1982.0043
Currently not on view
Location
Currently not on view
date made
ca 1929
maker
H. K. Mulford Company
ID Number
MG.M-02690
catalog number
M-02690
accession number
107349
Currently not on view
Location
Currently not on view
date made
ca 1940
maker
Parke, Davis and Company
ID Number
MG.M-04894.14
accession number
155762
catalog number
M-04894.14
According to 1940 product literature supplied by Parke, Davis & Company:"The name 'I'mmunogen' identifies the specific antigenic substances obtained from he surface or ectoplasm of bacterial cells.
Description
According to 1940 product literature supplied by Parke, Davis & Company:
"The name 'I'mmunogen' identifies the specific antigenic substances obtained from he surface or ectoplasm of bacterial cells. This type of antigen has been designated as 'ecto-antigen'"'
"The power of Immunogens to stimulate the production of immune bodies is high and compares favorably with that of other specific antigen used for similar purposes. / Immunogens are indicated when stimulation of the natural defense mechanism of immunity is desirable in the prophylaxis or treatment of acute and chronic infections."
"Immunogens are administered by injection. Intracutaneous, subcutaneous, and intramuscular routes are used most commonly; Immunogens may be given intravenously in small doses if desired. Subcutaneous injection is usually followed by more local reaction than intramuscular."
"Clinical Indications: Immunogens are applicable in the same class of cases as bacterial vaccines - for specific immunization. Both are antigenic - capable of stimulating the production of antibodies; and both are specific, the bacteriology of the infection under treatment pointing to the proper vaccine or Immunogen to be used. / The advantage of Immunogens lies, not in greater specificity, but in greater freedom from nonessential and possibly irritating elements. They contain comparatively little protein. Therefore, they can often be used with good effect in acute infections where vaccines would be less desirable."
Location
Currently not on view
date made
ca 1938
maker
Parke, Davis and Company
ID Number
MG.M-04670
catalog number
M-04670
accession number
147292
The indications or uses for this product as provided by the manufacturer are:An antibacterial serum obtained from horses immunized with suspensions of live influenza baccilli isolated from fatal cases of influenzal meningitis.
Description
The indications or uses for this product as provided by the manufacturer are:
An antibacterial serum obtained from horses immunized with suspensions of live influenza baccilli isolated from fatal cases of influenzal meningitis. Used in treatment of cerebrospinal meningitis caused by the influenza bacillus. Dose -- 30cc injected intraspinally, intracisternally, orintravenously.
Location
Currently not on view
date made
ca 1939
maker
Parke, Davis and Company
ID Number
MG.M-04858
accession number
154611
catalog number
M-04858
Currently not on view
Location
Currently not on view
date made
ca 1940
maker
Parke, Davis and Company
ID Number
MG.M-04894.15
accession number
155762
catalog number
M-04894.15
World War II propelled vaccine development and influenza research. Nobody wanted a repeat of the pandemic that devastated the troops and general population in WWI.
Description (Brief)
World War II propelled vaccine development and influenza research. Nobody wanted a repeat of the pandemic that devastated the troops and general population in WWI. The influenza virus had finally been identified, and the problem of how to grow it (in chicken eggs) was largely solved. “Prepared in the extra-embryonic fluid of the chick embryo” is stated prominently on this package of one of the earliest influenza virus vaccines.
Location
Currently not on view
date made
1945 - 1946
expiration date
1946-12-25
maker
Parke, Davis and Company
ID Number
MG.M-06427
catalog number
M-06427
accession number
173771
Currently not on view
Location
Currently not on view
date made
ca 1952
expiration date
1952-07-03
maker
E. R. Squibb and Sons
ID Number
1978.0882.05
accession number
1978.0882
catalog number
1978.0882.05
Currently not on view
Location
Currently not on view
date made
ca 1975
expiration date
1975-03-13
maker
Eli Lilly and Company
ID Number
1982.0043.036
accession number
1982.0043
catalog number
1982.0043.036
Currently not on view
Location
Currently not on view
date made
ca 1950s
maker
Parke, Davis and Company
ID Number
1982.0043.014A
accession number
1982.0043
catalog number
1982.0043.014A
Currently not on view
Location
Currently not on view
date made
ca 1951
expiration date
1951-04-01
maker
Eli Lilly and Company
ID Number
1985.0475.849
accession number
1985.0475
catalog number
1985.0475.849
Currently not on view
Location
Currently not on view
date made
ca 1949
expiration date
1950-03-06
maker
Lederle Laboratories Division, American Cyanimid Company
ID Number
MG.M-06548
catalog number
M-06548
accession number
183169
Currently not on view
Location
Currently not on view
date made
ca 1975
expiration date
1975-02-05
maker
Parke, Davis and Company
ID Number
1982.0043.003A
catalog number
1982.0043.003A
accession number
1982.0043
The indications or uses for this product as provided on its packaging:For cough, bronchitis, hoarseness, catarrhal winter colds, la grippe, colds, headacheCurrently not on view
Description
The indications or uses for this product as provided on its packaging:
For cough, bronchitis, hoarseness, catarrhal winter colds, la grippe, colds, headache
Location
Currently not on view
Date made
ca 1920
maker
M. B. Butler
ID Number
MG.M-10426.38
catalog number
M-10426
accession number
246707
Currently not on view
Location
Currently not on view
date made
ca 1940
maker
Parke, Davis and Company
ID Number
1978.0882.16
accession number
1978.0882
catalog number
1978.0882.16
Currently not on view
Location
Currently not on view
date made
ca 1973
expiration date
1973-12-10
maker
Parke, Davis and Company
ID Number
1982.0043.004
accession number
1982.0043
catalog number
1982.0043.004
The indications or uses for this product as provided by the manufacturer are:Coughs, colds, bronchitis, sore throat, hoarseness, loss of voice, croup, influenza, whooping coughCurrently not on view
Description
The indications or uses for this product as provided by the manufacturer are:
Coughs, colds, bronchitis, sore throat, hoarseness, loss of voice, croup, influenza, whooping cough
Location
Currently not on view
date made
1906 -1908
maker
Dr. B. J. Kay Medical Company
Saratoga Medical Company
ID Number
MG.293320.1216
accession number
293320
catalog number
293320.1216
Currently not on view
Location
Currently not on view
date made
ca 1940
maker
Parke, Davis and Company
ID Number
1978.0882.23
accession number
1978.0882
catalog number
1978.0882.23
Currently not on view
Location
Currently not on view
date made
ca 1976
expiration date
1976-12-15
maker
American Cyanamid Company. Lederle Laboratories Division
ID Number
1980.0076.011
accession number
1980.0076
catalog number
1980.0076.011
Currently not on view
Location
Currently not on view
Date made
ca 1965
product expiration date
1965-03-03
maker
National Drug Company
Richardson-Merrell, Inc
ID Number
1981.0170.001
catalog number
1981.0170.001
accession number
1981.0170
Currently not on view
Location
Currently not on view
date made
ca 1975
expiration date
1975-02-05
maker
Parke, Davis and Company
ID Number
1982.0043.003B
catalog number
1982.0043.003B
accession number
1982.0043

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