What’s the connection between the 1918 Pandemic, penicillin, and stimulant medications? In this post, I’ll explain the indirect and direct connections.
The 1918 Pandemic, also called the Spanish Flu, was only one in that era’s series of pandemics. They swept through successively in the late 1800s and early 1900s.
Influenza killed millions of people. But the dead weren’t the only victims. The survivors often suffered cruel fates, including Encephalitis Lethargica. Also called the Sleeping Sickness.
As we continue to struggle through the COVID-19 pandemic, I found important parallels to the 1918 Pandemic, including devastatingly lingering maladies.
- Post 1 provides an overview: Linking 1918 Flu Pandemic to Critical Medical Discoveries
- Post 2 detailed a shocking but little known effect among pediatric pandemic survivors: criminality. Some say it created a dramatic shift in societal perceptions of criminals as possibly made, not born: Post 1918 Pandemic: Children Develop the Disease of Criminals
- Here in Part 3, I share with you two fascinating medical discoveries sparked by past pandemics. Both breakthroughs happened accidentally and went ignored for years. The stories behind them—specifically the connection to influenza pandemics—remain largely unknown today.
Let’s take one discovery at a time.
1928: Influenza Researcher Discovers Penicillin
A shy and taciturn influenza researcher discovered penicillin. But that wasn’t his intention.
The accounts describing his discovery vary in small details. But here is the gist.
Scottish physician and bacteriologist Alexander Fleming was born in 1881. He served as an Army Medic during World War II. He saw many soldiers perish—not always from battle wounds but from the ensuing infection. Existing antiseptics typically did more harm than good. Moreover, bacteria in deep wounds persisted despite antiseptics.
In 1928, Fleming was studying a common type of bacteria, staphylococcus. He had filled a petri dish with the stuff. Reportedly, Fleming was not the most—a-hem —organized person. He forgot to place the dish into the incubator before he took a two-week vacation. The dish sat undisturbed on his cluttered desk, in the open air.
Upon his return, a surprised Fleming saw a clear, bacteria-free zone in the petri dish. It was later identified as containing the world-changing antibiotic, penicillin.
Some accounts say a a random dust speck landed in the dish. Others say an airborne mold spore from a nearby lab culturing molds had drifted up the stairwell. Either way, Fleming is credited as saying:
When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I suppose that was exactly what I did.
Can you imagine what happened next? Oh, wait, I already told you. Yes, Fleming’s enormous discovery languished—for 17 years.
Finally, in the 1940s, a pair of scientists took up the banner. They figured out how to mass produce Penicillin for use during World War II. With Fleming, they received a Nobel Prize in 1945.
1935: Dr. Bradley’s Stimulating Discovery
In 1935, seven years after Fleming’s discovery, came another medical breakthrough. A stimulant called Benzedrine reduced what we would later recognize as ADHD-like symptoms. (By the way, 1935 is 86 years ago.)
As with penicillin, the discovery:
1. Was related to a viral infection (itself possibly linked to the Spanish Flu),
2. Happened by accident, and
3. Went ignored for many years.
(I briefly relate the story in Is It You, Me, or Adult A.D.D.? To my knowledge, that was the first mention in a consumer book. Since then, 2008, it is a better known story.)
Did Big Pharma cook up this scheme? No, Charles Bradley, MD, reportedly sought to ease an x-ray procedure’s painful after-effects in his pediatric patients.
Now it’s true that manufacturer Smith, Kline & French (SKF) supplied Benzedrine to doctors interested finding new uses for it. So, yes, in an indirect way, a pharmaceutical company seeking to widen a product’s market made possible Bradley’s discovery. But he didn’t seek to use Benzedrine to alter children’s behavior. That was the surprise.
Rather, Bradley speculated that Benzedrine might ease children’s headaches following a painful diagnostic procedure. It was called a Pneumoencephalogram — the neuroimaging of its day.
Introduced in 1919, the procedure involved performing a lumbar puncture, removing a small volume of cerebrospinal fluid, and injecting air, oxygen, or helium in its place. The injection sharpens the X-rayed outlines of various brain structures. Hence the pain Bradley sought to relieve. We could say that without the 1918 pandemic, stimulant medications as a treatment for ADHD would have at least been much delayed.
Discovered in Hospital Founded by Grieving Parents
This experiment took place in one of the first psychiatric hospitals for children. The grieving parents of a child who survived Encephalitis Lethargica—but was never herself again—founded the hospital.
Learning about Bradley’s story is important for two major reasons:
1. It counters the myth that ADHD medications arose as a profiteering gambit to transform children into compliant drones.
2. It reminds us that, less than 100 years ago, most children with mental illness or behavior disorders went ignored—or warehoused.
The Societal Backdrop
1. Parenting Advice of the Time
Consider the prevailing child-raising sentiment from a prominent psychologist. According to Terrible Parenting Advice from the 1920s:
American psychologist John B. Watson cautioned parents to avoid giving children too much love and affection in his book Psychological Care of Infant and Child (1928):
“Never hug and kiss [children], never let them sit in your lap. If you must, kiss them once on the forehead when they say good night. Shake hands with them in the morning…
“Try it out. In a week’s time you will find how easy it is to be perfectly objective with your child and at the same time kind. You will be utterly ashamed of the mawkish, sentimental way you have been handling it.”
It’s important to note: The majority of behaviorally disturbed children ended up in custodial care homes or training schools.
2. The Wave of Pediatric EL Survivors
For wealthy industrialist George Lathrop Bradley, the tragedy hit close to home. He learned first-hand that viral encephalitis often accompanied those early pandemics. It left surviving children with severe neurological symptoms—but no place to care for them. Even for people with plenty of money.
His beloved only child, Emma (pictured above), fell victim in 1887 to viral encephalitis. Her lasting effects included mental retardation, cerebral palsy, and epilepsy.
Despite the best treatment that money could buy for 18 years, Emma showed no improvement. George and wife Helen began to accept their daughter’s fate. Yet they wanted to spare other families from their desperate struggle to find help.
In their wills, the couple requested that the family’s Providence (RI) estate become a treatment facility for children, . Established in 1931, the home’s mission was clear: Serving and conducting research to benefit poor children suffering from untreatable brain disorders. It was named the Emma Pendleton Bradley Hospital (pictured below).
The Rhode Island-based hospital still operates today. It is recognized as the nation’s first psychiatric hospital devoted exclusively to children and adolescents.
3. Charles Bradley, MD, Pioneering Pediatric Psychiatrist
In the 1930s, few child psychiatrists practiced in the U.S. — or anywhere. Dr. Bradley was one of them. He was a strong advocate for child psychiatry including biological and environmental factors. This complex, nuanced view was rather revolutionary for the time.
Thanks in part to the Encephalitis Lethargica (EL) epidemic, plenty of children needed help. As covered in post 1 in this series, the EL epidemic spread throughout Europe and North America during the 1920s. It devastated adults. But it had a uniquely disturbing effect on some child survivors: dysregulated behaviors that included criminality
Dr. Bradley worked at the Emma Pendleton Bradley Hospital, founded by his uncle, George Lathrop Bradley.
The home was a called a “beacon of light”. This home, like Bradley, took an innovative approach that integrated environmental and biological treatments.
Bradley’s First Benzedrine Experiments
Beginning in the 1920s, a stimulant called Benzedrine stood center stage as the nasal decongestant. Inspiration came from a 5,000-year-old Chinese herbal remedy for asthma. It contained the active ingredients ephedrine and pseudoephedrine and was called ma huang.
Turns out, Benzedrine didn’t work well for asthma. Yet, you could purchase it in a Vicks-type inhaler to relieve swollen nasal passages. The medical community also promoted it for raising low blood pressure and treating depression.
As mentioned previously, Dr. Bradley theorized that Benzedrine might ease children’s painful headaches following a now-primitive radiologic procedure. Unfortunately, the Benzedrine did little for the headaches. Yet, it had another, remarkable effect.
“Failure” Yields Surprising Results
Bradley expected increased alertness among the study subjects. After all, this was a known effect of stimulants in adults. A few children did become more alert — to the point of aggression. Others responded in an astonishingly positive way.
Unaware of the treatment, surprised teachers reported to Bradley that these children showed a striking improvement in their schoolwork and their behavior.
To see a single daily dose of Benzedrine produce a greater improvement in school performance than the combined efforts of a capable staff working in a most favorable setting would have been all but demoralizing to the teachers had not the improvement been so gratifying from a practical viewpoint.
Bradley followed this serendipitous result with a controlled trial of 30 children. Each child’s behavior disorder was severe enough to have warranted hospitalization, he reported. But the patients’ intelligence was generally within the normal range.
Of the 30 children, 14 responded in a “spectacular fashion”. The teachers noted an increased interest in school materials, increased performance, and increased drive to accomplish. The responses went beyond learning and schoolwork, though:
Children who had been raucous, aggressive, and domineering became easier-going and congenial. Instead of loudly quarreling, they discussed their differences more civilly. Instead of darting around pestering others, they settled down to play or read.
Other children showed (please read this closely; it is crucial to understanding the profound ways in which medication can affect individuals with ADHD):
A sense of well-being . . . a widening of interest in all things around them, and a diminished tendency to be preoccupied with themselves. More alertness, more initiative, and in general were “more self-sufficient and mature”.
Ignored for Half Century
Reportedly, the beneficial effects started the first day of Benzedrine treatment. The effects halted on the first day treatment stopped. As we know, stimulants can take effect quickly—and clear the system within hours.
Bradley and his colleagues published their findings in prominent journals. The media reported them. The medical community largely ignored Bradley’s finding.
At that time, as I mentioned in an earlier post, psychoanalysis predominated. Was that the main reason? Hard to say. But 25 years passed before anyone attempted to replicate his study. Another 25 years passed before stimulants became used for ADHD in children.
We find medical history littered with such gaps. As my scientist-husband says, “Sometimes the Old Guard has to die before new ideas gain greater acceptance.” Harsh but we find plenty of historical examples.
Take scurvy, leading killer of 18th Century seafarers and other explorers. A cure existed as early as 1497, when explorer Vasco de Gama’s crew discovered the power of citrus. Yet, this cure became lost, forgotten, rediscovered, confused, misconstrued, and generally made hash of for hundreds of years.
In fact, by the 1870s the “citrus cure” was discredited. For nearly sixty years, scurvy—despite being preventable and curable, with scientific research to back it up—continued killing people! The victims included men on Robert Falcon Scott’s 1911 expedition to the South Pole.
This went on until vitamin C was finally isolated in 1932 during research on guinea pigs. That came three years before Bradley’s discovery.
Even today, medical experts say that it generally takes at least 20 years for medical evidence to trickle down to the clinical level.
(I’m still waiting for the 1994 official DSM diagnosis of Adult ADHD to find its way more fully in the medical and mental-healthcare establishment!)
Two Potential Explanations for Lag
But there are at least two other reasons, it seems, as to why Bradley’s experiment did not spark more discovery.
1. Bradley Saw a Paradox
Bradley couldn’t explain what he saw as a paradox. That is, the stimulant drug produced subdued behavior in half the children but stimulated behavior in the other half.
Medical-science historian Madeleine P. Strohl writes on this point (Bradley’s Benzedrine Studies on Children with Behavioral Disorders. The Yale journal of biology and medicine. 84. 27-33, 2011):
There appeared to be no correlations between the effect of Benzedrine and the conventional clinical characteristics of sex, age, history, physical condition, and reaction type. Bradley also could not typify a child based on his or her changes in behavior.
These paradoxical responses led him to conclude that social behavior had an emotional and unstable nature, which he acknowledged was not a sufficient explanation.
Although Benzedrine seemed to play a significant role in behavior modification, Bradley stressed that the drug could only offer a supplementary approach to the treatment of behavioral problems because of its inconsistencies.
He reflected: “This approach in no sense replaces that of modifying a child’s surroundings and so removing the sources of conflict . . . Neither can it offer the same assurance of mental health as do forms of psychotherapy which enable a child to work out his emotional problems”
This conclusion followed his model of misbehavior as both social maladjustment and organic disease.
Obviously, Bradley was a cautious man, hewing to the evidence. His caution probably benefitted the legitimacy of ADHD in the long run. In the short run, however, many children did not receive the help they needed.
2. The Amphetamine Epidemic of 1921-1971
The other potential explanation for the lack of scientific interest in this discovery? It happened during the Amphetamine Epidemic of 1921-1971. Yes, that’s a huge time span.
Benzedrine had legitimate medical uses. Yet, some people also took it “recreationally” – that is, abused the drug. How many “drug abusers” actually had ADHD and found legitimate cognitive benefit from the Benzedrine? We’ll never know.
I wrote briefly about this here, featuring an amazing vintage animation: Did Mrs. Murphy Abuse Benzedrine—Or Did She Have ADHD?
1955: Ritalin Arrives
Twenty years after Dr. Bradley’s remarkable discovery, a milder version of Benzedrine came on the market. The year was 1955. The medication was Ritalin.
Many factors led to the rise of diagnosis and medical treatment of ADHD, first in children and much later in adults.
For now, I seek only to explain the complex historical circumstances behind this beneficial discovery, in the context of an earlier pandemic to the one we are living through now:
- The stimulant’s effect became known by accident, in 1935, when a doctor sought to ease children’s post-operative pain, not to change behavior
- This doctor worked in a privately funded, compassionately run home for children with psychiatric and behavioral issues—a rarity in that time, especially with the pediatric pandemic survivors desperately needing such care
- The hospital’s founders were parents who wanted to help children like their daughter, who suffered from post-influenza encephalitis and other neurological illnesses for which there was no available care.
Next up: the final post in this 4-part series examines how the adult victims of Encephalitis Lethargica spurred neuroscientist Oliver Sacks’ experiments with Parkinson’s drug L-Dopa. Robin Williams starred in the movie based on Sacks’ book: Awakenings.