How a Deadly Fire Gave Birth to Modern Medicine
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."
Scientists aim to preserve donkeys, one frozen embryo at a time
Every day for a week in 2022, Andres Gambini, a veterinarian and senior lecturer in animal science at the University of Queensland in Australia, walked into his lab—and headed straight to the video camera. Trained on an array of about 50 donkey embryos, all created by Gambini’s manual in vitro fertilization, or IVF, the camera kept an eye on their developmental progress. To eventually create a viable embryo that could be implanted into a female donkey, the embryos’ cells had to keep dividing, first in two, then in four and so on.
But the embryos weren’t cooperating. Some would start splitting up only to stop a day or two later, and others wouldn’t start at all. Every day he came in, Gambini saw fewer and fewer dividing embryos, so he was losing faith in the effort. “You see many failed attempts and get disappointed,” he says.
Gambini and his team, a group of Argentinian and Spanish researchers, were working to create these embryos because many donkey populations around the world are declining. It may sound counterintuitive that domesticated animals may need preservation, but out of 28 European donkey breeds, 20 are endangered and seven are in critical status. It is partly because of the inbreeding that happened over the course of many years and partly because in today’s Western world donkeys aren’t really used anymore.
“That's the reason why some breeds begin to disappear because humans were not really interested in having that specific breed anymore,” Gambini says. Nonetheless, in Africa, India and Latin America millions of rural families still rely on these hardy creatures for agriculture and transportation. And the only two wild donkey species—Equus africanus in Africa and Equus hemionus in Asia—are also dwindling, due to losing their habitats to human activities, diseases and slow reproduction rates. Gambini’s team wanted to create a way to preserve the animals for the future. “Donkeys are more endangered than people realize,” he says.
There’s much more to donkeys' trouble though. For the past 20 or so years, they have been facing a huge existential threat due to their hide gelatin, a compound derived from their skins by soaking and stewing. In Chinese traditional medicine, the compound, called ejiao, is believed to have a medicinal value, so it’s used in skin creams, added to food and taken in capsules. Centuries ago, ejiao was a very expensive luxury product available only for the emperor and his household. That changed in the 1990s when the Chinese economy boomed, and many people were suddenly able to afford it. “It went from a very elite product to a very popular product,” says Janneke Merkx, a campaign manager at The Donkey Sanctuary, a United Kingdom-based nonprofit organization that keeps tabs on the animals’ welfare worldwide. “It is a status symbol for gift giving.”
Having evolved in the harsh and arid mountainous terrains where food and water were scarce, donkeys are extremely adaptable and hardy. But the Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement.
The Chinese donkey population was quickly decimated. Unlike many other farm animals, donkeys are finicky breeders. When stressed and unhappy, they don’t procreate, so growing them in large industrial settings isn’t possible. “Donkeys are notoriously slow breeders and really very difficult to farm,” says Merkx. “They are not the same as other livestock like sheep and pigs and cattle.” Within years the, the donkey numbers in China dropped precipitously. “China used to have the largest donkey population in the world in the 1990s. They had 11 million donkeys, and it's now down to less than 3 million, and they just can't keep up with the demand.”
To keep the ejiao conveyor going, some producers turned to the illegal wildlife trade. Poachers began to steal and slaughter donkeys from rural villages in Africa. The Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement. Exactly how many creatures were lost to the skin trade to-date isn’t possible to calculate, says Faith Burden, the Donkey Sanctuary’s director of equine operations. Traditionally a poor people’s beast of burden, donkey counts are hard to keep track of. “When an animal doesn't produce meat, milk or eggs or whatever edible product, they're often less likely to be acknowledged in a government population census,” Burden says. “So reliable statistics are hard to come by.” The nonprofit estimates that about 4.8 million are slaughtered annually.
During their six to seven thousand years of domestication, donkeys rarely got the full appreciation for their services. They are often compared to horses, which doesn’t do them justice. They’re entirely different animals, Burden says. Built for speed, horses respond to predators and other dangers by running as fast as they can. Donkeys, which originate from the rocky, mountainous regions of Africa where running is dangerous, react to threats by freezing and assessing the situation for the best response. “Those so-called stubborn donkeys that won’t move as you want, they are actually thinking ‘what’s the best approach,’” Burden says. They may even choose to fight the predators rather than flee, she adds. “In some parts of the world, people use them as guard animals against things like coyotes and wolves.”
Scientists believe that domestic donkeys take their origin from Equus africanus or African wild ass, originally roaming where Kenya, Ethiopia and Eritrea are today. Having evolved in the harsh and arid mountainous terrains where food and water were scarce, they are extremely adaptable and hardy. Research finds that they can go without water for 72 hours and then drink their fill without any negative consequences. Their big jaws let them chew tough desert shrubs, which horses can’t exist on. Their large ears help dissipate heat. Their little upright hooves are a perfect fit for the uneven rocky or other dangerous grounds. Accustomed to the mountain desert climate with hot days and cold nights, they don’t mind temperature flux.
“The donkey is the most supremely adapted animal to deal with hostile conditions,” Burden says. “They can survive on much lower nutritional quality food than a cow, sheep or horse. That’s why communities living in some of the most inhospitable places will often have donkeys with them.” And that’s why losing a donkey to an illegal skin trade can devastate a family in places like Eritrea. Suddenly everything from water to firewood to produce must be carried by family members—and often women.
Workers unloading donkeys at the Shinyanga slaughterhouse in Tanzania. Fearing a future in which donkeys go extinct, scientists have found ways to cryopreserve a donkey embryo in liquid nitrogen.
TAHUCHA
One can imagine a time when worldwide donkey populations may dwindle to the point that they would need to be restored. That includes their genetic variability too. That’s where the frozen embryos may come in handy. We may be able to use them to increase the genetic variability of donkeys, which will be especially important if they get closer to extinction, Gambini says. His team had already created frozen embryos for horses and zebras, an idea similar to a seed bank. “We call this concept the Frozen Zoo.”
Creating donkey embryos proved much harder than those of zebras and horses. To improve chances of fertilization, Gambini used the intracytoplasmic sperm injection or ICSI, in which he employed a tiny needle called a micropipette to inject a donkey sperm into an egg. That was a step above the traditional IVF method, in which the egg and a sperm are left floating in a test tube together. The injection took, but during the incubating week, one after the other, the embryos stopped dividing. Finally, on day seven, Gambini finally spotted the exact sight he was hoping to see. One of the embryos developed into a burgeoning ball of cells.
“That stage is called a blastocyst,” Gambini says. The clump of cells had a lot of fluids mixed within them, which indicated that they were finally developing into a viable embryo. “When we see a blastocyst, we know we can transfer that into a female.” He was so excited he immediately called all his collaborators to tell them the good news, which they later published in the journal of Theriogenology.
The one and only embryo to reach that stage, the blastocyst was cryopreserved in liquid nitrogen. The team is waiting for the next breeding season to see if a female donkey may carry it to term and give birth to a healthy foal. Gambini’s team is hoping to polish the process and create more embryos. “It’s our weapon in the conservation ass-enal,” he says.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
Too much of this ingredient leads to autoimmune diseases, new research shows. Here's how to cut back.
For more than a century, doctors have warned that too much salt in your diet can lead to high blood pressure, heart disease and stroke - and many of the reasons for these effects are well known. But recently scientists have been looking deeper, into the cellular level, and they are finding additional reasons to minimize sodium intake; it is bad for immune cells, creating patterns of gene expression and activity seen in a variety of autoimmune diseases such as multiple sclerosis, lupus, rheumatoid arthritis, and type-1 diabetes.
Salt is a major part of the ocean from which life evolved on this planet. We carry that legacy in our blood, which tastes salty. It is an important element for conducting electrical signals along nerves and balancing water and metabolites transported throughout our bodies. We need to consume about 500 milligrams of salt each day to maintain these functions, more with exercise and heavy sweating as that is a major way the body loses salt. The problem is that most Americans eating a modern western diet consume about 3400 milligrams, 1.5 teaspoons per day.
Evidence has been accumulating over the last few years that elevated levels of sodium can be harmful to at least some types of immune cells. The first signal came in monocytes, which are immune cells that travel to various tissues in the body, where some of them turn into macrophages, a subset of white blood cells that can directly kill microorganisms and make chemical signals that bring other types of immune cells into play.
Two years ago, Dominik N. Müller from the Max-Delbrueck-Center in Berlin, Germany and Markus Kleinewietfeld, an immunologist at Hasselt University in Belgium, ran a study where they fed people pizza and then measured their immune cell function. “We saw that in any monocytes, metabolic function was down, even after a single salty meal,” Kleinewietfeld says. It seemed to be the cellular equivalent of the sluggish feeling we get after eating too much. The cells were able to recover but more research is needed to answer questions about what dose of sodium causes impairment, how long the damage lasts, and whether there is a cumulative effect of salt toxicity.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations.
The latest series of experiments focused on a type of T cell called T regulatory cells, or Tregs. Most T cells release inflammatory mediators to fight pathogens and, once that job is done, Tregs come along to calm down their hyperactive brethren. Failure to do so can result in continued inflammation and possibly autoimmune diseases.
In the lab, Kleinewietfeld and his large team of international collaborators saw that high levels of sodium had a huge effect on Tregs, upregulating 1250 genes and downregulating an additional 1380 genes so that they looked similar to patterns of gene expression seen in autoimmune diseases.
Digging deeper, they found that sodium affected mitochondria, the tiny organelles inside of cells that produce much of its energy. The sodium was interfering with how the mitochondria use oxygen, which resulted in increased levels of an unstable form of oxygen that can damage cell function. The researchers injected those damaged Tregs into mice and found that they impaired the animals' immune function, allowing the inflammation to continue rather than shutting it down.
That finding dovetailed nicely with a 2019 paper in Nature from Navdeep Chandel's lab at Northwestern University, which showed in mice that inhibiting the mitochondrial use of oxygen reduced the ability of Tregs to regulate other T cells. “Mitochondria were controlling directly the immunosuppressive program, they were this master regulator tuning the right amount of genes to give you proper immunosuppression,” Chandel said. “And if you lose that function, then you get autoimmunity.”
Kleinewietfeld's team studied the Treg cells of humans and found that sodium can similarly decrease mitochondrial use of oxygen and immunosuppressive activity. “I would have never predicted that myself,” Chandel says, but now researchers can look at the mitochondria of patients with autoimmune disease and see if their gene expression also changes under high salt conditions. He sees the link between the patterns of gene expression in Tregs generated by high salt exposure and those patterns seen in autoimmune diseases, but he is cautious about claiming a causal effect.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations. He says a high salt diet could also have an indirect effect on immune function through the way it affects the gut microbiome and the molecules made by microbes when they break down food. But the research results are too preliminary to say that for sure, much less parse out the role of salt compared with other possible factors. “It is still an exciting journey to try to understand this field,” he says.
Additionally, it is difficult to say precisely how this research in animals and human cell cultures will translate into a whole human body. Individual differences in genetics can affect how the body absorbs, transports, and gets rid of sodium, such that some people are more sensitive to salt than are others.
So how should people apply these research findings to daily life?
Salt is obvious when we sprinkle it on at the table or eat tasty things like potato chips, but we may be unaware of sodium hidden in packaged foods. That's because salt is an easy and cheap way to boost the flavor of foods. And if we do read the labeled salt content on a package, we focus on the number for a single serving, but then eat more than that.
Last September, the U.S. Food and Drug Administration (FDA) began a process to update labels on the content of food, including what is meant by the word “healthy” and how food manufacturers can use the term. Many in the food industry are resisting those proposed changes.
Chandel cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker.
Until labels are updated, it would be prudent to try to reduce sodium intake by cutting down on packaged foods while making your own food at home, where you know just how much salt has been added. The Mayo Clinic offers guidance on how to become more aware of the sodium in your diet and eat less of it.
Chandel thinks many people will struggle with minimizing salt in their diets. It’s similar to the challenge of eating less sugar, in that the body craves both, and it is difficult to fight that. He cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker. “Dietary antioxidants have failed in just about every clinical trial, yet the public continues to take them,” Chandel says. But he is optimistic that research will lead us to a better understanding of how Tregs function, and uncover new targets for treating autoimmune diseases.