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Rockefeller Research Institute during Great Flu in 1918

The Rockefeller Research Institute during Great Flu in 1918

In April 1917, the then President of the United States, Thomas Woodrow Wilson, declared the United States to join the First World War without sufficient preparation. Soon, a pandemic flu that affected one-third of the world's population broke out in the United States, and then abused and poisoned the souls. It is estimated that this flu caused at least 50 million deaths worldwide, making it one of the most catastrophic public health events in modern history. 
The wave of influenza that began in the spring of 1918 was mild, and the second wave was fierce, focusing on attacking young and middle-aged people. The symptoms of some patients are quite serious, the body becomes purple and black, the mucosa bleeds severely, and even causes the bleeding of the Qiqiao, just like the black death that swept Europe in the Middle Ages.

After the declaration of war, in order to encourage the morale of the army and mobilize the people into the world war, the US government implemented a strict news censorship system. 

In the early days of the disease outbreak, the governments of various regions concealed the epidemic situation, which caused the pandemic flu to stand on the winning side in the beginning of this war without smoke.

Government Corrupt and Dirty Environment

It is extremely ironic that, on the basis of knowing that an epidemic has already occurred. On September 28, 1918, in order to sell millions of dollars of war bonds, Philadelphia, a government with corrupt and dirty environment, held a large march of hundreds of thousands of people as scheduled . Within seventy-two hours after the parade, all 31 hospital beds in the city were full and patients died one after another.

Due to the wrong decision of the US government, the pandemic quickly spread and the epidemic spread worldwide. Hundreds of millions of people around the world cannot get medical treatment and care from medical staff. They can only try various folk earthworks, and even use hypothetical deceptive drugs-some people have camphor pills and garlic hanging on their necks, and some people gargle with disinfectant.

 In 1918, under the dual influence of war and disease, the life expectancy of Americans fell from 51 years to 39 years. As of the 1920 influenza mitigation period, the pandemic had killed 675,000 Americans and thousands of American children have been orphaned.

If we do not understand pneumonia and influenza from the context of disease research and biological development in the twentieth century, we will not be able to fully understand the battle between humans and influenza, and it will be difficult to understand epidemiology in depth. At the beginning of the twentieth century, the United States had just launched medical school education reforms and founded several scientific institutes that would become famous in the future. Among them, the Rockefeller Institute (Rockefeller Institute), founded in 1901, is the leader in the field of biomedicine. In 1912, the Alexis Carrel won the first American Nobel Prize. 

Anyone who has a little understanding of the history of the 1918 flu pandemic knows that this flu started in the military, and it is the frequent movement of military personnel that has exacerbated the outbreak and epidemic of influenza. Let's start with the story of the Rockefeller Institute and the army.

Army's only affiliated laboratory

In the early days of the Rockefeller Institute, the first director, Simon Flexner recruited talents all over the world, and Carrel came from France. 
When the World War broke out, some researchers returned to their homeland to join the war, and even died in battle. 
At that time, William Welch, chairman of the Scientific Advisory Board of the Rockefeller Institute and a professor at Hopkins University, happened to be the president of the American Academy of Sciences. 
He had no intention of leading the Academy of Sciences to participate in research on war science and technology until he accepted the advice of astronomer George Hale. 

Welch expressed his attitude to President Wilson, expressing his willingness to assist and ensure that members of the Academy of Sciences were unconditionally recruited into the military in preparation for the war.

At the beginning of the war, only more than 700 of the hundreds of the thousands of doctors in the United States served in the Army or Navy. 
The military needs tens of thousands of doctors and so does the demand for scientists. 

Welch, who is over-aged and overweight, was enlisted in the army, and his proud student Flexner was also enlisted. 
In order to prevent scientists from losing their talents as volunteers or enlisted in the army, Flaxner advised Welch to integrate the entire Rockefeller Institute into the military. 

Welch made recommendations to the Army Military Medical Director William Gorgas, and then the Rockefeller Institute became the only military-affiliated laboratory affiliated to the US Army. Flexner served as an army medical consultant and was responsible for various business transactions.

There must be bloody slaughter in war, and wound infection is a problem that military hospitals must face. At that time, antibiotics were not known. 

As early as 1916, Karel, who returned to France for a vacation, had persuaded the authorities to build a special hospital for him in Compiegne, France. He hopes that he can combine research and treatment in this temporary hospital and find a better way to solve the problem of wound infection. 

British biochemist Henry B Dakin joined Carrel's team in time. 
In the end, they invented a new wound treatment plan, the Carrel-Dakin diagnosis and treatment plan, which can prevent the wounded soldiers from further deteriorating in the direction of sepsis.
Simulation for Rockefeller Research Institute during Great Flu in 1918

In July 1917, with the support of the Rockefeller Foundation, the Institute built a War Demonstration Hospital for more than a month. The temporary hospital is located in the southwest corner of the institute and consists of fifteen movable wooden houses. 

The original intention of the hospital was to teach surgical procedures to newly recruited doctors, introduce the latest Carrel-Dakin diagnosis and treatment plan, and provide free treatment and care to patients. 

At the Rockefeller Institute, the work of scientists was reconstructed: 
Almost all research was related to war, and the institute became a teaching ground for military medicine. 
The bacteriologist Oswald Avery taught bacteriology, and the virologist Peyton Rous turned to studying the preservation of blood. Using his method, people established the first blood bank on the front in 1917.

Aerial view of the War Demonstration Hospital of Rockefeller Institute and the design of the War Demonstration Hospital (1917)

Pneumonia Research

At the time, the mechanism of many diseases was not very clear. Although the word "virus" existed as early as 1898, the source of its infection has never been known to scientists, so that for decades, virus research has remained at the theoretical level.

In 2019, the concurrent disease of COVID-19 is pneumonia, commonly known as new coronary pneumonia. In 2003, the concurrent disease of SARS (Severe Acute Respiratory Syndrome) was also pneumonia, commonly known as atypical pneumonia. 

The flu is precisely caused by pneumonia. As an acute respiratory infection caused by viruses, bacteria or fungi that affects the lungs, pneumonia was once listed as "the first death of humans". 

Until 1936, it occupied the number one killer in the United States, even in today's world. Pneumonia is also the leading cause of childhood death.

Before the establishment of the Institute Hospital, Flexner hoped that the hospital would focus on several diseases: poliomyelitis, lobar pneumonia, syphilis, heart disease, and intestinal infantilism. 

In 1910, when Rufus Cole became the president of the hospital, he decided to devote most of his and his team's energy to pneumonia research. 

Serum against a certain Pneumococcus

In 1912, Cole developed an immune serum against a certain type of pneumococcus, which played a role in the treatment. 
At this time, Avery published a paper on the subject of secondary infections of tuberculosis patients, which impressed Cole.

At the invitation of Cole, Avery joined the institute in 1913. 
Just as the entire Western world was preparing for war, Cole, Avery and their colleagues were about to test their immune sera on humans.
In 1917, the Institute published a ninety-page monograph "Prevention and Serum Treatment of Acute Lobar Pneumonia" by Cole and Avery et al. 

It not only detailed the method for preparing and using serum for treating pneumonia for the first time, but also predicted that pneumonia would break out in the military camp. 

In October 1917, Gogas recommended that the officers of the military hospital send more doctors to the Rockefeller Institute to learn how to prepare and use this serum.

The end of 1917 and the beginning of 1918, were the coldest winter ever in the eastern Rocky Mountains. 

Flaxner has also warned that in the boot camp where the population density is large and the sources of people are different, people will bring all kinds of diseases together, and everyone may suffer from diseases that have not been experienced before. 
This situation will intensify due to chaotic management and lack of adequate medical conditions. 
Before the outbreak of the first flu, measles had appeared in recruit training, and measles will also be complicated by pneumonia. 
Therefore, in early 1918, Gogas asked Welch to prepare a special committee for pneumonia and act as chairman. Welch hesitated, calling Flexner.
The two reached a consensus that Cole was the best person to chair the committee. They met in Washington and selected members of the Pneumonia Committee, which was backed by strong research by Gogas, Welch, Flexner and academic background. 

In early 1918, Cole personally led a team to Fort Sam Houston, Texas to study pneumonia. 
In June and August of 1918, an early member of the institute, Eugene L. Opie, went to Camp Funston, Kansas and Camp Pike, Arkansas to study the epidemic.

For a long time, Haemophilus influenzae has been mistaken as the pathogen of influenza. 
This bacteria was isolated in 1892 by German bacteriologist Richard Pfeiffer in patients with influenza and was once called "Pfeiffer". 

When scientists concluded that the fatal disease of 1918 was influenza, biomedical laboratories around the world turned to H. influenzae. 
Some laboratories have been successfully separated, while others have gained nothing. 
Even Paul Lewis, who once found the culprit virus of poliomyelitis with Frexner and developed a vaccine, said that the major influenza was caused by Haemophilus influenzae, even though he once suspected that the causative agent might A virus.

Haemophilus influenzae

Unfortunately, Lewis later gave up on the possibility of the virus causing flu. At first, he did not find Haemophilus influenzae in the diseased tissue. 
Later, he not only succeeded, he also developed a vaccine with others, and then wanted to make immune serum. 
At the time, William Park, the laboratory director of the New York City Department of Public Health, the best municipal public health department in the world, and his partner Anna Williams said in early 1919 that Haemophilus influenzae would not cause influenza. They also suspect that it is a filtered virus. 

Unfortunately, before that, they had isolated Haemophilus influenzae from patients and became the first people to announce that Haemophilus influenzae may be a causative agent to develop a vaccine.

In October 1918, Avery heard reports from dozens of researchers all over the world who were also looking for Haemophilus influenzae, with success and failure. 

Avery carefully made no conclusions and made no speculations, nor did he claim to have found the cause of the flu in any report. 

However, Avery found that 30% of healthy people in the Rockefeller Institute had Haemophilus influenzae. 

Just like many healthy people also carry pneumococcus in their mouths, but they will not get pneumonia. 

Modern scientific research tells us that Haemophilus influenzae is a normal flora of human upper respiratory tract, and the actual pathogenic range is extremely wide.

Over time, more and more scientists have admitted that the causative agent of pandemic influenza may not be Haemophilus influenzae but an unidentified filtered virus.

Discovery of influenza virus

The whole world was completely attacked by the flu, and the war was over. 

By 1920, the deadly flu had also eased, and the slaughter ended. After several years of research on Haemophilus influenzae, Avery devoted all his time and energy to pneumonia research and achieved impressive results. 

He found that a polysaccharide capsule wrapped around pneumococcus can also cause an immune response, broadening the scientists' horizons, not only proteins or protein-containing substances can stimulate the immune system to respond.

After that, Avery signed fewer and fewer papers. 
He had not published any papers for seven years. 
Until 1944, he and his collaborators published about pneumococcus in the journal Experimental Medicine
The article on genetic transformation in the paper pointed out that the real substance that caused the transformation of bacteria was DNA instead of protein, subverting the traditional view that protein was genetic material at the time. 

Science historian Horace Judson commented that his paper is quite the legacy of nineteenth-century scientific research: 
The writing is smooth and compact, the arguments are conclusive, clear and cautious, and from beginning to end everyone feels Avery retains the work Curiosity and strong curiosity.

Avery has never been married for life, and has been busy learning, versatile, and likes to be alone. He was nominated for the Nobel Prize several times, but failed to win the laurel crown. 

Some people said he might be gay, and some people said that the Nobel Prize Committee originally intended to reward him for his work on pneumonia. 

At that time, he studied pneumococcus and found that the genetic material was DNA (deoxyribonucleic acid). Of course, the most credible should be Judson’s statement: 
The Nobel Prize Committee noted Avery ’s work on the discovery of genetic material, and they are waiting for his further discovery. After all, his discovery was too cutting-edge, and many scientists could not understand it. 

Even Joshua Lederberg, who was deeply influenced by him and later proved the sexual reproduction of bacteria, thought that reading the paper was painful.
The Nobel Prize Committee needs to wait for the results of others.

And another very popular character, bacteriologist Lewis, after the flu, fell to the trough of life and never climbed out again. 
When he was still studying at the University of Pennsylvania, he devoted himself to experimental research.

After leaving the Flaxner laboratory, he was in charge of the Henry Phipps Institute at Penn University from 1910 to 1923. 

In the latter part of his reign, due to lack of funds for the institute, he had to work hard in the upper class and strive to raise funds to become the scientific darling of the Philadelphia nobles. 

But this worldly life bored him, and he was extremely painful, hoping to find a quiet place in which to display his talents in the research. For this reason, he even repeatedly rejected the University of Iowa's invitation. 

The University of Iowa hopes that he will create a first-class research institute, funded by the state government. 
However, this position will force him to leave the laboratory.
 For Lewis, the animal pathology division of the Rockefeller Institute in Princeton was the ideal destination, when it was a desolate place surrounded by farms and countryside. 

At the age of forty-four, he set aside high salaries, fame, and family, and returned to the Rockefeller Institute in 1923.

Rockefeller University is located on the side entrance of 67th Street in New York City to commemorate Avery

Before Lewis passed away, he had no choice but to recruit a brilliant young scientist, Richard Shope. Chop ’s father was an outstanding doctor and a farmer. Along the direction of his father, Chop obtained a medical degree from the University of Iowa, and then taught pharmacology for a year at the medical school, and also carried out some animal experiments.

Given his outstanding performance in tuberculosis research, he joined Lewis' team. In 1928, forced by his livelihood and other considerations, he left Lewis' tuberculosis research field and turned to pig disease.

In 1929, in sick pigs suffering from swine flu, Hopp and Lewis isolated Haemophilus swine influenza, a bacterium similar to Haemophilus influenzae. 
However, he found that the bacteria will not cause swine flu. After Lewis's death, he independently conducted research.

In 1931, he discovered a virus in sick pig tissue. He inoculated the virus to pigs, and the pigs had only mild symptoms.
Later, when he injected the virus and Haemophilus swine flu into the pig at the same time, the pig got a serious disease. 
This experiment not only proved that viruses can cause influenza, but also explained for the first time the mechanism by which viruses and bacteria cause disease together.

Hemophilus influenzae suis

When he thought that the 1918 flu pandemic abused the world, the pigs in the Midwest of the United States also suffered from a new disease, and many pigs were dying. 
So, Schop examined the immunological characteristics of survivors during the 1918 pandemic and those born after the end of the flu in 1920.
 The results of the experiment showed that the former group had antibodies against the swine flu virus, and the latter did not. 
This proves that there was a very close relationship between human flu and swine flu in 1918, even though they may not be caused by the same virus.
 Inspired by Shoop's research. Soon, British researchers Andrews (Christopher Andrews) and collaborators identified the first human influenza virus. 
Andrews and Schoop have also maintained a lifelong friendship since then. 

A few years later, several different laboratories, including the results of laboratory experiments by Schoop himself, showed that the influenza virus may have spread to swine in 1918 and caused swine flu. The swine flu and human flu were probably caused by a virus.

Conclusion and inspiration

In an emergency, scientists are under tremendous pressure. 
In the race against the disease, most scientists panicked and followed the medical giant Pfeiffer all the way. 
Even the Rockefeller Institute devoted to the two wars failed to find a solution in time to prevent the epidemic spreading rapidly. 
Among the group of scientists, Avery was sober. While he was studying Haemophilus influenzae, he did not completely give up pneumonia research. After the end of the flu, he returned to freedom and concentrated on his areas of interest. Finally in 1944, at the age of 67, he published a heavy paper that shocked the entire field of biology and became one of the pioneers in the field of modern molecular biology.

Essentially, Avery's pursuit of scientific issues is persistent. However, this kind of attachment sometimes brutally destroys a highly gifted scientist. 
If Shoop followed Lewis and continued to study tuberculosis without turning to the field of swine disease, perhaps the discovery of human influenza virus had nothing to do with him. 
The process of influenza virus discovery also leaves humans with the revelation: science will not change its laws because things are pressing, it needs a calm heart and time.

Author's Bio

Doctor Shawna Reason, Virologist
Dr. Shawna Reason
Name: Shawna Reason

Education: MBBS, MD

Occupation: Medical Doctor / Virologist 

Specialization: Medical Science, Micro Biology / Virology, Natural Treatment

Experience: 15 Years as a Medical Practitioner

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