Did Thomas Francis Jr. Isolate Influenza A in 1934?

“Epidemiology must constantly seek imaginative and ingenious teachers and scholars to create a new genre of medical ecologists who, with both the fine sensitivity of the scientific artist, and the broad perception of the community sculptor, can interpret the interplay of forces which result in disease.”

—Thomas Francis, Jr.

After the British trio of Smith, Andrewes, and Laidlaw were heralded with “isolating” Influenza A in 1933, we Americans became jealous and needed our own hero to claim successful “isolation” of the same “virus.” Enter Thomas Francis Jr.:

“Thomas Francis, Jr., (born July 15, 1900, Gas City, Ind., U.S.—died Oct. 1, 1969, Ann Arbor, Mich.), American microbiologist and epidemiologist who isolated the viruses responsible for influenza A (1934) and influenza B (1940) and developed a polyvalent vaccine effective against both strains.”

https://www.britannica.com/biography/Thomas-Francis-Jr

It’s kind of ironic that the Britannica gives credit for the “isolation” of Influenza A and B to the American while their section on Britains very own Smith, Andrewes, and Laidlaw has no mention of any isolation of influenza A whatsoever:

“In 1933 the British investigators Wilson Smith, Christopher H. Andrewes, and Patrick P. Laidlaw were able to transmit influenza to ferrets, and the influenza virus was subsequently adapted to mice.”

https://www.britannica.com/biography/Wilson-Smith

According to the Britannica, Smith, Andrewes, and Laidlaw only transmitted influenza, they did not isolate it. This raises the question, how does one transmit something one has never actually isolated nor proven to exist?

Interestingly, the Britannica’s account of events actually conflicts with that of the American CDC:

“Wilson Smith, Christopher Andrewes, and Patrick Laidlaw isolated influenza A virus in ferrets in 1933, and Thomas Francis Jr. isolated Influenza B virus in 1936.”

https://www.cdc.gov/vaccines/pubs/pinkbook/flu.html

It seems we Americans give credit to Smith, Andrewes, and Laidlaw for the “isolation” of Influenza A and Francis Jr. for the “isolation” of Influenza B. The CDC even has a completely different year for the supposed isolation of influenza B. According to the CDC, Francis Jr. isolated it in 1936 while the Britannica has Francis Jr. isolating it in 1940. 

Thomas Francis Jr.

This is a either a nice example of gracious acknowledgement of the pseudoscientific accomplishments between two countries or an interesting game of hot-potato where neither side wants the credit. Whose account of the fictional isolation of influenza is correct? We may never know. However, we can look to Francis Jr.’s supposed “isolation” of Influenza A to see if he actually did what the British (but not the CDC) claim he did:

TRANSMISSION OF INFLUENZA BY A
FILTERABLE VIRUS

“The studies of Shope on swine influenza established the fact that a filterable virus is the essential factor in the production and transmission of the disease. In 1933, Smith, Andrewes and Laidlaw reported that the intranasal inoculation of ferrets with nasal or pharyngeal washings from human cases of epidemic influenza produced a disease in those animals charcacterized by fever and catarrhal swelling of the nasal mucous membranes, but without detectable pathological lesions in the viscera. They were able to transfer the disease in ferrets by the intranasal inoculation of suspensions of the ground turbinate bones. The causative agent was found to be a filterable virus. The animals invariably recovered from the disease, and the serum of a recovered animal was found to neutralize the action of the virus. They were also able to produce a similar disease in ferrets with the virus of swine influenza. Shope was able to confirm their observations on the infectivity of the virus of swine influenza for ferrets. He observed, however, that when the ferrets were inoculated intranasally under light ether anesthesia, pulmonary consolidation was an invariable accompaniment of the disease, the infection was more severe, and death of the animal sometimes occurred. Suspensions of the lungs of infected animals were found to contain a high concentration of the virus.

Last winter a number of ferrets were inoculated in this laboratory with material from various respiratory infections, including common colds, acute tonsilitis, lobar pneumonia, psittacosis and two cases of clinical influenza. In only one instance, and that distinctly of bacterial origin, was infection established in the ferret.

During the latter part of August and September of 1934, an epidemic of respiratory infection occurred in Puerto Rico. In its clinical course it appeared to be typical epidemic influenza, although the mortality was low. On September 10, 1934, through the kindness of Drs. nT.C. Earle and W. A. Sawyer, of the International Health Board, specimens of sputum in 50 percent glycerine, from 5 typical cases, were received. Three of the specimens were separated from the glycerine, washed and emulsified in Locke’s solution. The material from each of these 3 cases was then inoculated intranasally into ferrets under ether anesthesia. On the second day after inoculation, each of the animals had an abrupt rise of temperature, which in one instance reached 106.5′ F. The latter animal (P. R. 5) was sacrificed on the third day after inoculation; the lungs and turbinates were removed and ground with sand and meat infusion broth. Two animals were then inoculated intranasally with unfiltered suspensions and one with a Berkefeld V filtrate of the material. All 3 animals developed fever in from 24 to 48 hours, and, since that time, consecutive
serial passages have been made in ferrets at 4 to 5 day intervals, with 5 percent broth suspensions of ferret lung tissue or with Berkefeld filtrates of the suspensions. In the sixth passage animal, pulmonary consolidation, bluish-red in color, was observed in the lower lobe of the left lung. In subsequent animals inoculated with either filtered or bacteria-free unfiltered material, the pulmonary lesions have been more extensive and have been consistently present through the twelfth passage. The subcutaneous injection of suspensions of lungs containing the infectious agent has elicited no evidence of the experimental disease.

In the course of the experimental work with ferrets, one of the laboratory workers (S. S.) developed symptoms typical of influenza. Nasal and pharyngeal washings inoculated intranasally induced the disease in a ferret without producing pulmonary consolidation. This strain was also transmissible from animal to animal with bacteria-free material.

The onset of fever in the animals occurs generally on the second day after inoculation. There is usually moderate apathy, lack of appetite and pallor of the nose. The catarrhal symptoms have been extremely variable. In animals with pulmonary consolidation, rapid, labored breathing and cough occur. Following the first fever, the temperature usually drops to normal and then rises again in from 24 to 48 hours. The course of the fever is not uniform. There have been no fatalities in the animals infected with the original strain which were allowed to run the entire course of the disease.

Grossly, the pulmonary involvement is usually of lobar distribution. The lung is bluish red in color. When cut, considerable moisture exudes from the tissue. The microscopical study of the involved lung of the ferret reveals a thickening of the alveolar walls with proliferation of the alveolar epithelial cells. The alveolar spaces contain, predominantly, large pink-staining cells resembling the alveolar phagocytes, many of which show degenerative changes. Polymorphonuclear leukocytes are not numerous except in the terminal bronchioles. There is also a pronounced perivascular round cell infiltration. Fibrin is scanty, but definite edema is present. The picture closely resembles the description by Shope of swine influenza in ferrets. It differs strikingly from the acute bacterial infections of the lung, but is not unlike the pulmonary lesions produced by pure virus infections, such as psittacosis in the monkey.

The present results confirm the observations of Smith, Andrewes and Laidlaw on the transfer of a filterable, transmissible agent from human cases of
epidemic influenza to ferrets. The character of the disease in the ferret differs from that described by the British authors, in that it is more severe and is accompanied by pulmonary consolidation. In these respects, the disease in our animals appears to resemble more closely the disease produced in ferrets by Shope, with swine influenza virus. There has been evidence to suggest the adaptation of the virus to the ferret, for with strain P. R. 5 distinct pulmonary lesions were first noted in the sixth passage animal.

A Berkefeld V filtrate of the sputum obtained from Puerto Rico (P. R. 5) was inoculated into 6 Swiss mice intracerebrally and intraperitoneally under ether anesthesia. Berkefeld V filtrates of suspensions of the lungs of the first and the fourth passage ferrets, administered to Swiss and white-faced mice by the intranasal, intracerebral and intraperitoneal routes, caused no demonstrable effect. In each instance the mice originally inoculated were sacrificed and passages made to new mice by the same routes.

On Septembey 21, the centrifuged but unfiltered lung suspension from the second passage ferret of the contact strain (S. S.) was inoculated into 3 white-faced and 3 Smiss mice by the intracerebral, intranasal and intraperitoneal routes. One of the white-faced mice died in 24 hours with generalized bacterial infection. On the second day, several of the mice appeared to be somewhat sick, and all were killed on the fourth day. No abnormalities were found. The lungs were ground with 20 cc of Locke’s solution, centrifuged, and 4 Swiss mice inoculated intranasally and intracerebrally. On the fourth day, when killed, consolidation of the upper portions of the lungs was found in 2 mice. Suspensions from these two lungs were given to 6 Swiss and 6 Rockefeller Institute mice intranasally. Several of the Swiss mice appeared ill, and 4 of the 6 had definite pulmonary lesions at autopsy on the fourth day. None of the mice of the Rockefeller Institute strain showed pulmonary involvement.

In the fifth passage, death of all 6 Swiss mice and of 2 of 6 of the Rockefeller Institute strain occurred in 48 hours. The surviving mice were killed. All showed extensive pulmonary consolidation involving most of the left lung and cardiac lobe, and usually part of the right upper and middle lobes. A Berkefeld V filtrate of a 10 percent lung suspension was then inoculated intranasally into 6 Swiss mice. This filtrate was found to be bacteriologically sterile in both aerobic and anaerobic cultures. Death occurred in these mice in from 48 to 72 hours, all animals showing marked pulmonary consolidation.

Subsequently, the inoculation of a 5 percent lung suspension, or Berkefeld V filtrates of from 5 to 10 percent suspensions of lung, caused death in Swiss mice in about 48 hours. Mice of the Rockefeller Institute strain survived somewhat longer. In practically all instances, direct cultures of the heart’s blood and of the cut lung surface have been free from bacteria. Cultures of the emulsified tissue in blood broth not infrequently reveal various Gram-negative bacilli, but they are usually few in number. These bacteria do not appear to be related to the disease process, since they are inconstantly observed. Furthermore, subsequent bacteria-free emulsions or
filtrates have been fully active.

This strain of infective agent (S. S.) has been passed through I1 series of mice. A suspension of the lungs from mice of the eighth serial passage inoculated intranasally into a ferret produced a characteristic febrile reaction. At the same time, different dilutions of the mouse lung suspension were made, and a small amount of each dilution was inoculated intranasally into 4 mice. By the seventh day all animals receiving a 1:1600 dilution, or more, had succumbed with typical pathology.

More recently, an unfiltered sterile lung suspension of a ferret, the tenth passage animal of the original Puerto Rico passage strain (P. R. 5) was transferred to mice. In the first mice, killed on the fourth day, only mild pulmonary lesions were seen. In the second passage, however, all died on the fourth day with typical extensive involvement. The mice of the third
passage, which received a bacteria-free 10 percent suspension of lung, died in 48 hours. These results are of special interest, since earlier attempts to transmit infection to mice with filtrates containing this strain were unsuccessful.

The lesions in the mouse’s lung tend to involve the entire lobe, spreading peripherally. The surface is smooth and bluish gray or reddish blue. When the trachea is cut, a copious foamy liquid exudes. The cut surface of the lung is rather viscid, but firm. Stained films usually reveal mononuclear cells, but no bacteria. Microscopical, there is thickening of the alveolar walls and a moderate amount of edema in the alveolar spaces. The degree of hyperemia is variable. There is a perivascular small round cell infiltration. The cellular reaction, unlike acute bacterial infections, is predominantly of the mononuclear cells. The number of polymorphonuclear leukocytes varies. In many of the cells degenerative changes are seen in the nuclei and protoplasm.

The results of the experiments, both in ferrets and mice, indicate that the agent producing the disease in these animals is a filterable virus. It has been possible to produce the infection with filtrates, which, in aerobic and anaerobic cultures, are bacteriologically sterile. The pulmonary lesions are bacteria-free. Furthermore, the microscopic pathology of the involved lung resembles that of pulmonary lesions produced by other virus infections, rather than that of bacterial infections.

In the current issue of The Lancet, Andrewes, Laidlaw and Smith report their success in transmitting to mice the viruses derived from both swine influenza and human influenza. The results in the present study are apparently in complete agreement with theirs. They have been able, in addition, by the use of specific antiserum from hyperimmune animals (horse and ferret), to neutralize the action of the respective viruses in mice.”

doi: 10.1126/science.80.2081.457-a.

In Summary:

  • According to Francis Jr., Shope’s work in 1931 on swine influenza established the “fact” that a filterable “virus” is the essential factor in the production and transmission of the disease
  • However, did Shope really establish this “fact?”
  • In 1933, Smith, Andrewes and Laidlaw reported that the intranasal inoculation of ferrets with nasal or pharyngeal washings from human cases of epidemic influenza produced a disease in those animals charcacterized by fever and catarrhal swelling of the nasal mucous membranes, but without detectable pathological lesions in the viscera
  • They were able to transfer the disease in ferrets by the intranasal inoculation of suspensions of the ground turbinate bones
  • The causative agent was found to be a filterable “virus”
  • However, was a “virus” really isolated in 1933?
  • In the previous winter, a number of ferrets were inoculated in the laboratory with material from various respiratory infections, including common colds, acute tonsilitis, lobar pneumonia, psittacosis and two cases of clinical influenza, yet in only one instance, said to be of bacterial origin, was infection established in the ferret
  • On September 10, 1934, through the International Health Board, specimens of sputum in 50 percent glycerine, from 5 typical cases of influenza from Puerto Rico, were received:
    1. Three of the specimens were separated from the glycerine
    2. Washed and emulsified in Locke’s solution
    3. The material from each of these 3 cases was then inoculated intranasally into ferrets under ether anesthesia
    4. On the second day after inoculation, each of the animals had an abrupt rise of temperature, which in one instance reached 106.5′ F
    5. The latter animal (P. R. 5) was sacrificed on the third day after inoculation; the lungs and turbinates were removed and ground with sand and meat infusion broth
    6. Two animals were then inoculated intranasally with unfiltered suspensions and one with a Berkefeld V filtrate of the material

A Quick Detour on Locke’s Solution

This is what was said to be in the Locke solution from a separate source. If this is what Francis Jr.’s solution actually contained is anyone’s best guess but it gives an idea as to all of the additives used:

“Locke’s salt solution (Locke, 1895)
The concentrations are given as gl l,OOO ml solution.

NaCI 9.0, KCI 0.42, CaCl2 0.24, and NaHC03 0.2, glucose 1.0 made up to 1,000 ml with distilled water.”

https://www.google.com/url?sa=t&source=web&rct=j&url=http://link.springer.com/content/pdf/bbm%253A978-4-431-67875-5%252F1.pdf&ved=2ahUKEwjlksvTiIjxAhWAAp0JHSnzArMQFjAKegQIBxAC&usg=AOvVaw0G6hwRFgzus0eQ0BHbZwgD

From the above ingredients list, we have a solution made up of sodium chloride (saline), potassium chloride, calcium chloride, sodium bicarbonate (baking soda), and glucose (sugar). The first 3 ingredients are commonly found in ice melts which can be toxic to animals:

Sodium chloride:

“Large ingestions of sodium chloride can lead to sodium toxicosis and a dose of 4g/kg of sodium chloride can be lethal to dogs. Mild ingestions lead only to gastrointestinal upset such as vomiting and diarrhea, but dogs eating large amounts of this type of ice melt can develop hypernatremia with central nervous system signs, dehydration, tachycardia, tachypnea, hyperthermia, and death.”

Potassium chloride:

“Increased intake of potassium, as seen with large ingestions of potassium chloride salts, is unlikely to produce sustained hyperkalemia unless renal excretion is impaired in the dog. Potassium chloride, however, is a severe irritant and can cause gastrointestinal irritation to the point of hemorrhagic vomiting or diarrhea.”

Calcium salts (calcium carbonate, calcium chloride, and calcium magnesium acetate):

“Calcium salts are the most hazardous as they are the most severe irritants of all the ingredients in ice melts. Ingestion of calcium salts can cause severe gastrointestinal signs as well as local irritation from dermal (skin and paws) contact. Large ingestions of calcium salts are unlikely to increase serum calcium concentrations because multiple other factors are needed to absorb the calcium.”

https://www.petpoisonhelpline.com/uncategorized/really-safe-ice-melt/

If these compounds can do this to pets licking their paws after walking on ice melt, what kind of damage would these compounds do after being injected into the nostrils of ferrets along with toxic glycerol, sand, ground up diseased tissues, meat broth, etc.?

End Detour

  • Consecutive serial passages were made in ferrets at 4 to 5 day intervals, with 5 percent broth suspensions of ferret lung tissue or with Berkefeld filtrates of the suspensions
  • The subcutaneous injection of suspensions of lungs containing the infectious agent elicited no evidence of the experimental disease
  • Symptoms usually consisted of:
    1. Moderate apathy
    2. Lack of appetite
    3. Pallor (paleness) of the nose
    4. Extremely variable catarrhal symptoms
    5. Rapid, labored breathing and cough (occurred only in animals with pulmonary consolidation)
  • The course of the fever was not uniform
  • There were no fatalities in the animals infected with the original strain which were allowed to run the entire course of the disease
  • The histological picture closely resembled the description by Shope of swine influenza in ferrets
  • It differed strikingly from the acute bacterial infections of the lung, but was said to be not unlike the pulmonary lesions produced by “pure virus” infections, such as psittacosis in the monkey
  • Francis Jr. claims his results confirm the findings of Smith, Andrewes, and Laidlaw but then states the character of the disease in the ferret differs from that described by the British authors in that it is more severe and is accompanied by pulmonary consolidation
  • He states that the disease in his animals appeared to resemble more closely the disease produced in ferrets by Shope with swine influenza “virus”
  • In other words, the disease Francis Jr. created in ferrets was more like the experimental swine flu than the experimental “human” flu
  • Transfers of the “virus” from ferret to mice were carried out as such:
    1. A Berkefeld V filtrate of the sputum obtained from Puerto Rico (P. R. 5) was inoculated into 6 Swiss mice intracerebrally and intraperitoneally under ether anesthesia
    2. Berkefeld V filtrates of suspensions of the lungs of the first and the fourth passage ferrets, administered to Swiss and white-faced mice by the intranasal, intracerebral and intraperitoneal routes, caused no demonstrable effect
    3. In each instance the mice originally inoculated were sacrificed and passages made to new mice by the same routes
    4. The centrifuged but unfiltered lung suspension from the second passage ferret of the contact strain (S. S.) was inoculated into 3 white-faced and 3 Smiss mice by the intracerebral, intranasal and intraperitoneal routes
    5. On the second day, several of the mice appeared to be somewhat sick, and all were killed on the fourth day yet no abnormalities were found
    6. The lungs were ground with 20 cc of Locke’s solution, centrifuged, and 4 Swiss mice inoculated intranasally and intracerebrally
    7. On the fourth day, when killed, consolidation of the upper portions of the lungs was found in 2 mice
    8. Suspensions from these two lungs were given to 6 Swiss and 6 Rockefeller Institute mice intranasally
    9. Several of the Swiss mice appeared ill, and 4 of the 6 had definite pulmonary lesions at autopsy on the fourth day.
    10. None of the mice of the Rockefeller Institute strain showed pulmonary involvement
    11. In the fifth passage, death of all 6 Swiss mice and of 2 of 6 of the Rockefeller Institute strain occurred in 48 hours and the surviving mice were killed
    12. A Berkefeld V filtrate of a 10 percent lung suspension was then inoculated intranasally into 6 Swiss mice and death occurred in these mice in from 48 to 72 hours
  • Cultures of the emulsified tissue in blood broth not infrequently revealed various Gram-negative bacilli, but they were usually few in number and they did not appear to be related to the disease process, since they are inconstantly observed
  • This strain of infective agent (S. S.) had been passed through I1 series of mice
  • A suspension of the lungs from mice of the eighth serial passage inoculated intranasally into a ferret produced a characteristic febrile (fever) reaction
  • At the same time, different dilutions of the mouse lung suspension were made, and a small amount of each dilution was inoculated intranasally into 4 mice
  • An unfiltered sterile lung suspension of a ferret, the tenth passage animal of the original Puerto Rico passage strain (P. R. 5) was transferred to mice
  • The results were of interest since earlier attempts to transmit infection to mice with filtrates containing this strain were unsuccessful
  • Francis Jr. concludes that the results of the experiments, both in ferrets and mice, indicated that the agent producing the disease in these animals is a filterable “virus”
  • The microscopic pathology of the involved lung resembled that of pulmonary lesions produced by other “virus” infections, rather than that of bacterial infections (which is fascinating since no “virus” had ever been purified/isolated so how would he know?)
  • Francis Jr. ends by claiming his results were apparently (as far as one knows or can see) in complete agreement with those of Smith, Andrewes, and Laidlaw

Reading through this mess of mad science experiments, it is clear as day no “virus” was ever properly purified nor isolated. Francis Jr. assumed that a “virus” was present in the samples and as is usually the case, instead of separation, he added various chemicals/compounds to the sample. He then ground up diseased animal tissues and injected the resulting mixture in numerous unnatural ways (nose, brain, stomach, etc) into various other animals. He would then kill the animals upon negative results. Francis Jr. repeated this horrific process of injecting toxic animal goo and killing/grinding up/injecting the diseased tissue into healthy animals until he finally got the desired results he wanted after numerous “passages.”

The CDC was right (for once) by not crediting Francis Jr. with the isolation of influenza A in 1934 as this never occurred in his paper. While Francis Jr. was able to claim that he successfully isolated a “virus,” he did nothing more than create experimental disease in a lab. The CDC was, however, wrong (as usual) for crediting the British trio with isolation in 1933. To date, the proper purification/isolation of an influenza A “virus” has never occurred.

3 comments

  1. Thank you Misto
    Always reassuring to see a telltale sign such as the Thomas Francis Jr photograph in the doorway of the Special Projects Research Building with address 1133…

    I know I am preaching to the choir but they make such claims of its a virus in the emulsified mixture of who knows what was really all included. I am sure sand in the throat is not abrasive…
    With each one of these studies it becomes extremely clear how everything is inverted. It puts the word quack in perspective. I wonder how much of this emulsified concoction was stuffed into a ferret. I wonder had they allowed the ferret the opportunity to decide if it would consume the concoction in a bowl what would have happened. But instead another unnatural way of transferring said concoction to the ferrets and this is called science.

    Liked by 1 person

    1. Yeah, the address caught my eye as well. 😉

      Virology is nothing but indirect results from inhumane mad science experiments used to create science fictional theories presented as fact. There is nothing logical about their methods. Anyone looking at this objectively would see the insanity of it all. It is mind-blowing that this has “sciemce” has passed unchallenged (for the most part) for nearly a century.

      Like

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