The Cocoanut Grove fire in Boston in 1942 tragically claimed 490 lives, but was the catalyst for several important medical advances.
On the evening of November 28, 1942, more than 1,000 revelers from the Boston College-Holy Cross football game jammed into the Cocoanut Grove, Boston's oldest nightclub. When a spark from faulty wiring accidently ignited an artificial palm tree, the packed nightspot, which was only designed to accommodate about 500 people, was quickly engulfed in flames. In the ensuing panic, hundreds of people were trapped inside, with most exit doors locked. Bodies piled up by the only open entrance, jamming the exits, and 490 people ultimately died in the worst fire in the country in forty years.
"People couldn't get out," says Dr. Kenneth Marshall, a retired plastic surgeon in Boston and president of the Cocoanut Grove Memorial Committee. "It was a tragedy of mammoth proportions."
Within a half an hour of the start of the blaze, the Red Cross mobilized more than five hundred volunteers in what one newspaper called a "Rehearsal for Possible Blitz." The mayor of Boston imposed martial law. More than 300 victims—many of whom subsequently died--were taken to Boston City Hospital in one hour, averaging one victim every eleven seconds, while Massachusetts General Hospital admitted 114 victims in two hours. In the hospitals, 220 victims clung precariously to life, in agonizing pain from massive burns, their bodies ravaged by infection.
The scene of the fire.
Boston Public Library
Tragic Losses Prompted Revolutionary Leaps
But there is a silver lining: this horrific disaster prompted dramatic changes in safety regulations to prevent another catastrophe of this magnitude and led to the development of medical techniques that eventually saved millions of lives. It transformed burn care treatment and the use of plasma on burn victims, but most importantly, it introduced to the public a new wonder drug that revolutionized medicine, midwifed the birth of the modern pharmaceutical industry, and nearly doubled life expectancy, from 48 years at the turn of the 20th century to 78 years in the post-World War II years.
The devastating grief of the survivors also led to the first published study of post-traumatic stress disorder by pioneering psychiatrist Alexandra Adler, daughter of famed Viennese psychoanalyst Alfred Adler, who was a student of Freud. Dr. Adler studied the anxiety and depression that followed this catastrophe, according to the New York Times, and "later applied her findings to the treatment World War II veterans."
Dr. Ken Marshall is intimately familiar with the lingering psychological trauma of enduring such a disaster. His mother, an Irish immigrant and a nurse in the surgical wards at Boston City Hospital, was on duty that cold Thanksgiving weekend night, and didn't come home for four days. "For years afterward, she'd wake up screaming in the middle of the night," recalls Dr. Marshall, who was four years old at the time. "Seeing all those bodies lined up in neat rows across the City Hospital's parking lot, still in their evening clothes. It was always on her mind and memories of the horrors plagued her for the rest of her life."
The sheer magnitude of casualties prompted overwhelmed physicians to try experimental new procedures that were later successfully used to treat thousands of battlefield casualties. Instead of cutting off blisters and using dyes and tannic acid to treat burned tissues, which can harden the skin, they applied gauze coated with petroleum jelly. Doctors also refined the formula for using plasma--the fluid portion of blood and a medical technology that was just four years old--to replenish bodily liquids that evaporated because of the loss of the protective covering of skin.
"Every war has given us a new medical advance. And penicillin was the great scientific advance of World War II."
"The initial insult with burns is a loss of fluids and patients can die of shock," says Dr. Ken Marshall. "The scientific progress that was made by the two institutions revolutionized fluid management and topical management of burn care forever."
Still, they could not halt the staph infections that kill most burn victims—which prompted the first civilian use of a miracle elixir that was being secretly developed in government-sponsored labs and that ultimately ushered in a new age in therapeutics. Military officials quickly realized this disaster could provide an excellent natural laboratory to test the effectiveness of this drug and see if it could be used to treat the acute traumas of combat in this unfortunate civilian approximation of battlefield conditions. At the time, the very existence of this wondrous medicine—penicillin—was a closely guarded military secret.
From Forgotten Lab Experiment to Wonder Drug
In 1928, Alexander Fleming discovered the curative powers of penicillin, which promised to eradicate infectious pathogens that killed millions every year. But the road to mass producing enough of the highly unstable mold was littered with seemingly unsurmountable obstacles and it remained a forgotten laboratory curiosity for over a decade. But Fleming never gave up and penicillin's eventual rescue from obscurity was a landmark in scientific history.
In 1940, a group at Oxford University, funded in part by the Rockefeller Foundation, isolated enough penicillin to test it on twenty-five mice, which had been infected with lethal doses of streptococci. Its therapeutic effects were miraculous—the untreated mice died within hours, while the treated ones played merrily in their cages, undisturbed. Subsequent tests on a handful of patients, who were brought back from the brink of death, confirmed that penicillin was indeed a wonder drug. But Britain was then being ravaged by the German Luftwaffe during the Blitz, and there were simply no resources to devote to penicillin during the Nazi onslaught.
In June of 1941, two of the Oxford researchers, Howard Florey and Ernst Chain, embarked on a clandestine mission to enlist American aid. Samples of the temperamental mold were stored in their coats. By October, the Roosevelt Administration had recruited four companies—Merck, Squibb, Pfizer and Lederle—to team up in a massive, top-secret development program. Merck, which had more experience with fermentation procedures, swiftly pulled away from the pack and every milligram they produced was zealously hoarded.
After the nightclub fire, the government ordered Merck to dispatch to Boston whatever supplies of penicillin that they could spare and to refine any crude penicillin broth brewing in Merck's fermentation vats. After working in round-the-clock relays over the course of three days, on the evening of December 1st, 1942, a refrigerated truck containing thirty-two liters of injectable penicillin left Merck's Rahway, New Jersey plant. It was accompanied by a convoy of police escorts through four states before arriving in the pre-dawn hours at Massachusetts General Hospital. Dozens of people were rescued from near-certain death in the first public demonstration of the powers of the antibiotic, and the existence of penicillin could no longer be kept secret from inquisitive reporters and an exultant public. The next day, the Boston Globe called it "priceless" and Time magazine dubbed it a "wonder drug."
Within fourteen months, penicillin production escalated exponentially, churning out enough to save the lives of thousands of soldiers, including many from the Normandy invasion. And in October 1945, just weeks after the Japanese surrender ended World War II, Alexander Fleming, Howard Florey and Ernst Chain were awarded the Nobel Prize in medicine. But penicillin didn't just save lives—it helped build some of the most innovative medical and scientific companies in history, including Merck, Pfizer, Glaxo and Sandoz.
"Every war has given us a new medical advance," concludes Marshall. "And penicillin was the great scientific advance of World War II."
Electricity is emerging as a powerful treatment for chronic ailments.
Kelly, a case manager for an insurance company, spent years battling both migraines and Crohn's, a disease in which the immune system attacks the intestines.
For many people, like Kelly, a stronger electric boost to the vagus nerve could be life-changing.
After she had her large intestine removed, her body couldn't absorb migraine medication. Last year, about twice a month, she endured migraines so bad she couldn't function. "It would go up to a ten, and I would rock, wait it out," she said. The pain might last for three days.
Then her neurologist showed her a new device, gammaCore, that tames migraines by stimulating a nerve—not medication. "I don't have to put a chemical in my body," she said. "I was thrilled."
At first, Kelly used the device at the onset of a migraine, applying electricity to her pulse at the front of her neck for six minutes. The pain peaked at about half the usual intensity--low enough, she said, that she could go to work. Four months ago, she began using the device for two minutes each night as prevention, and she hasn't had a serious migraine since.
The Department of Defense and Veterans Administration now offer gammaCore to patients, but it hasn't yet been approved by Medicare, Medicaid, or most insurers. A month of therapy costs $600 before insurance or a generous financial assistance program kicks in.
A patient uses gammaCore, a non invasive vagal nerve stimulator device that was FDA approved in November 2018, to treat her migraine.
(Photo captured from a patient video at gammacore.com)
If the poet Walt Whitman wrote "I Sing The Body Electric" today, he might get specific and point to the vagus nerve, a bundle of fibers that run from the brainstem down the neck to the heart and gut. Singing stimulates it—and for many people, like Kelly, a stronger electric boost to the nerve could be life-changing.
The mind-body connection isn't just an idea — the vagus nerve literally carries signals from the mind to the body and back. It may explain the link between childhood trauma and illnesses such as chronic pain and headaches in adults. "How is it possible that a psychological event causes pain years later?" asked Peter Staats, co-founder of electroCore, which has won approval for its new device from the Food and Drug Administration (FDA) for both migraine and cluster headaches. "There has to be a mind-body interface, and that is the vagus nerve," he said.
Scientists knew that this nerve controlled your heart rate and blood pressure, but in the past decade it has been linked to both pain and the immune system.
"Everything is gated through the vagus -- problems with the gut, the heart, and the lungs," said Chris Wilson, a researcher at Loma Linda University, in California. Wilson is studying how vagus nerve stimulation (VNS) could help pre-term babies who develop lung infections. "Nearly every one of our chronic diseases, including cancer, Alzheimer's, Parkinson's, chronic arthritis and rheumatoid arthritis, and depression and chronic pain…could benefit from an appropriate stimulator," he said.
It's unfortunate that Kelly got her device only after her large intestine was gone. SetPoint Medical, a privately held California company founded to develop electronic treatments for chronic autoimmune diseases, has announced early positive results with VNS for both Crohn's and rheumatoid arthritis.
As SetPoint's chief medical officer, David Chernoff, put it, "We're hacking into the nervous system to activate a system that is already there," an approach that, he said, could work "on many diseases that are pain- and inflammation-based." Inflammation plays a role in much modern illness, including depression and obesity. The FDA already has approved VNS for both, using surgically implanted devices similar to pacemakers. (GammaCore is external.)
The history of VNS implants goes back to 1997, when the FDA approved one for treating epilepsy and researchers noticed that it rapidly lifted depression in epileptic patients. By 2005, the agency had approved an implant for treatment-resistant depression. (Insurance companies declined to reimburse the approach and it didn't take off, but that might change: in February, the Center for Medicare and Medicaid Services asked for more data to evaluate coverage.) In 2015, the FDA approved an implant in the abdomen to regulate appetite signals and help obese people lose weight.
The link to inflammation had emerged a decade earlier, when researchers at the Feinstein Institute for Medical Research, in Manhasset, New York, demonstrated that stimulating the nerve with electricity in rats suppressed the production of cytokines, a signaling protein important in the immune system. The researchers developed a concept of a hard-wired pathway, through the vagus nerve, between the immune and nervous system. That pathway, they argued, regulates inflammation. While other researchers argue that VNS is helpful by other routes, there is clear evidence that, one way or another, it does affect immunity.
At the same time, investors are seeking alternatives to drugs.
The Feinstein rat research concluded that it took only a minute a day of stimulation and tiny amounts of energy to activate an anti-inflammatory reflex. This means you can use devices "the size of a coffee bean," said Chernoff, much less clunky than current pacemakers—and advances in electronic technology are making them possible.
At the same time, investors are seeking alternatives to drugs. "There's been a push back on drug pricing," noted Lisa Rhoads, a managing director at Easton Capital Investment Group, in New York, which supported electroCore, "and so many unintended consequences."
In 2016, the U.S. National Institutes of Health began pumping money into relevant research, in a program called "Stimulating Peripheral Activity to Relieve Conditions," which focuses on "understanding peripheral nerves — nerves that connect the brain and spinal cord to the rest of the body — and how their electrical signals control internal organ function."
GlaxoSmithKline formed Galvani Bioelectronics with Google to study miniature implants. It had already invested in Action Potential Venture Capital, in Cambridge, Massachusetts, which holds SetPoint and seven other companies "that are all targeting a nerve to treat a chronic disease," noted partner Imran Eba. "I see a future in which bioelectronics medicine is competing directly with drugs," he said.
Treating the body with electricity could bring more ease and lower costs. Many people with serious auto-immune disease, for example, have to inject themselves with drugs that cost $60,000 a year. SetPoint's implant would cost less and only need charging once a week, using a charger worn around the neck, Chernoff said. The company receives notices remotely and can monitor compliance.
Implants also allow the treatment to target a nerve precisely, which could be important with Parkinson's, chronic pain, and depression, observed James Cavuoto, editor and publisher of Neurotech Reports. They may also allow for more fine-turning. "In general, the industry is looking for signals, biomarkers that indicate when is the right time to turn on and turn off the stimulation. It could dramatically increase the effectiveness of the therapy and conserve battery life," he said.
Eventually, external devices could receive data from biomarkers as well. "It could be something you wear on your wrist," Cavuoto noted. Bluetooth-enabled devices could communicate with phones or laptops for data capture. External devices don't require surgery and put the patient in charge. "In the future you'll see more customer specification: Give the patient a tablet or phone app that lets them track and modify their parameters, within a range. With digital devices we have an enormous capability to customize therapies and collect data and get feedback that can be fed back to the clinician," Cavuoto said.
Slow deep breathing, the traditional mind-body intervention, is "like watching Little League. What we're doing is Major League."
It's even possible to stimulate the vagus through the ear, where one branch of the bundle of fibers begins. In a fetus, the tissue that becomes the ear is also part of the vagus nerve, and that one bit remains. "It's the same point as the acupuncture point," explained Mark George, a psychiatrist and pioneer researcher in depression at Medical University of South Carolina in Charleston. "Acupuncture figured out years ago by trial and error what we're just learning about now."
Slow deep breathing, the traditional mind-body intervention, also affects the vagus nerve in positive ways, but gently. "That's like watching Little League," Staats, the co-founder of electroCore, said. "What we're doing is Major League."
In ten years, researcher Wilson suggested, you could be wearing "a little ear cuff" that monitors your basic autonomic tone, a heart-attack risk measure governed in part by the vagus nerve. If your tone looked iffy, the stimulator would intervene, he said, "and improve your mood, cognition, and health."
In the meantime, we can take some long slow breaths, read Whitman, and sing.
