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."
Henrietta Lacks' Cells Enabled Medical Breakthroughs. Is It Time to Finally Retire Them?
For Victoria Tokarz, a third-year PhD student at the University of Toronto, experimenting with cells is just part of a day's work. Tokarz, 26, is studying to be a cell biologist and spends her time inside the lab manipulating muscle cells sourced from rodents to try to figure out how they respond to insulin. She hopes this research could someday lead to a breakthrough in our understanding of diabetes.
"People like to use HeLa cells because they're easy to use."
But in all her research, there is one cell culture that Tokarz refuses to touch. The culture is called HeLa, short for Henrietta Lacks, named after the 31-year-old tobacco farmer the cells were stolen from during a tumor biopsy she underwent in 1951.
"In my opinion, there's no question or experiment I can think of that validates stealing from and profiting off of a black woman's body," Tokarz says. "We're not talking about a reagent we created in a lab, a mixture of some chemicals. We're talking about a human being who suffered indescribably so we could profit off of her misfortune."
Lacks' suffering is something that, until recently, was not widely known. Born to a poor family in Roanoke, VA, Lacks was sent to live with her grandfather on the family tobacco farm at age four, shortly after the death of her mother. She gave birth to her first child at just fourteen, and two years later had another child with profound developmental disabilities. Lacks married her first cousin, David, in 1941 and the family moved to Maryland where they had three additional children.
But the real misfortune came in 1951, when Lacks told her cousins that she felt a hard "knot" in her womb. When Lacks went to Johns Hopkins hospital to have the knot examined, doctors discovered that the hard lump Henrietta felt was a rapidly-growing cervical tumor.
Before the doctors treated the tumor – inserting radium tubes into her vagina, in the hopes they could kill the cancer, Lacks' doctors clipped two tissue samples from her cervix, without Lacks' knowledge or consent. While it's considered widely unethical today, taking tissue samples from patients was commonplace at the time. The samples were sent to a cancer researcher at Johns Hopkins and Lacks continued treatment unsuccessfully until she died a few months later of metastatic cancer.
Lacks' story was not over, however: When her tissue sample arrived at the lab of George Otto Gey, the Johns Hopkins cancer researcher, he noticed that the cancerous cells grew at a shocking pace. Unlike other cell cultures that would die within a day or two of arriving at the lab, Lacks' cells kept multiplying. They doubled every 24 hours, and to this day, have never stopped.
Scientists would later find out that this growth was due to an infection of Human Papilloma Virus, or HPV, which is known for causing aggressive cancers. Lacks' cells became the world's first-ever "immortalized" human cell line, meaning that as long as certain environmental conditions are met, the cells can replicate indefinitely. Although scientists have cultivated other immortalized cell lines since then, HeLa cells remain a favorite among scientists due to their resilience, Tokarz says.
"People like to use HeLa cells because they're easy to use," Tokarz says. "They're easy to manipulate, because they're very hardy, and they allow for transection, which means expressing a protein in a cell that's not normally there. Other cells, like endothelial cells, don't handle those manipulations well."
Once the doctors at Johns Hopkins discovered that Lacks' cells could replicate indefinitely, they started shipping them to labs around the world to promote medical research. As they were the only immortalized cell line available at the time, researchers used them for thousands of experiments — some of which resulted in life-saving treatments. Jonas Salk's polio vaccine, for example, was manufactured using HeLa cells. HeLa cell research was also used to develop a vaccine for HPV, and for the development of in vitro fertilization and gene mapping. Between 1951 and 2018, HeLa cells have been cited in over 110,000 publications, according to a review from the National Institutes of Health.
But while some scientists like Tokarz are thankful for the advances brought about by HeLa cells, they still believe it's well past time to stop using them in research.
"Am I thankful we have a polio vaccine? Absolutely. Do I resent the way we came to have that vaccine? Absolutely," Tokarz says. "We could have still arrived at those same advances by treating her as the human being she is, not just a specimen."
Ethical considerations aside, HeLa is no longer the world's only available cell line – nor, Tokarz argues, are her cells the most suitable for every type of research. "The closer you can get to the physiology of the thing you're studying, the better," she says. "Now we have the ability to use primary cells, which are isolated from a person and put right into the culture dish, and those don't have the same mutations as cells that have been growing for 20 years. We didn't have the expertise to do that initially, but now we do."
Raphael Valdivia, a professor of molecular genetics and microbiology at Duke University School of Medicine, agrees that HeLa cells are no longer optimal for most research. "A lot of scientists are moving away from HeLa cells because they're so unstable," he says. "They mutate, they rearrange chromosomes to become adaptive, and different batches of cells evolve separately from each other. The HeLa cells in my lab are very different than the ones down the hall, and that means sometimes we can't replicate our results. We have to go back to an earlier batch of cells in the freezer and re-test."
Still, the idea of retiring the cells completely doesn't make sense, Valdivia says: "To some extent, you're beholden to previous research. You need to be able to confirm findings that happen in earlier studies, and to do that you need to use the same cell line that other researchers have used."
"Ethics is not black and white, and sometimes there's no such thing as a straightforward ethical or unethical choice."
"The way in which the cells were taken – without patient consent – is completely inappropriate," says Yann Joly, associate professor at the Faculty of Medicine in Toronto and Research Director at the Centre of Genomics and Policy. "The question now becomes, what can we do about it now? What are our options?"
While scientists are not able to erase what was done to Henrietta Lacks, Joly argues that retiring her cells is also non-consensual, assuming – maybe incorrectly – what Henrietta would have wanted, without her input. Additionally, Joly points out that other immortalized human cell lines are fraught with what some people consider to be ethical concerns as well, such as the human embryonic kidney cell line, commonly referred to as HEK-293, that was derived from an aborted female fetus. "Just because you're using another kind of cell doesn't mean it's devoid of ethical issue," he says.
Seemingly, the one thing scientists can agree on is that Henrietta Lacks was mistreated by the medical community. But even so, retiring her cells from medical research is not an obvious solution. Scientists are now using HeLa cells to better understand how the novel coronavirus affects humans, and this knowledge will inform how researchers develop a COVID-19 vaccine.
"Ethics is not black and white, and sometimes there's no such thing as a straightforward ethical or unethical choice," Joly says. "If [ethics] were that easy, nobody would need to teach it."
Social isolation. Strange pathogens outside. Strategic resource planning. Our Earthbound pandemic-driven social distancing could be mistaken for adapting to another, foreign planet. After all, we're donning all our protective apparel to go on an airplane or to the grocery store, nevertheless to just open our front door. Perhaps this is training for the world galactic visionaries Elon Musk, Jeff Bezos, and Richard Branson see in our future.
"There are parallels to the individual psychological experience, but from an operational standpoint, it is too different."
Ready to go live on Mars or something? Not so fast, experts say. The experience of shelter in place isn't parallel to being a space settler, or even an astronaut.
"Certain aspects are similar, but still, honestly, there are too many differences to say it preps us," says Angelo Vermeulen, co-founder of the art-science collective SEADS (Space Ecologies Art and Design) Network. In 2013, he served as a NASA crew commander for a four-month Mars-on-Earth mission, isolated in a geometric biodome with five others. "There are parallels to the individual psychological experience, but from an operational standpoint, it is too different. You don't need a spacesuit, aren't threatened by a thin atmosphere or worried about being overpowered by radiation."
Outside threats aside, we have a bigger experience gap: Most of us didn't see this pandemic coming and weren't trained to survive the current new normal. NASA astronauts get at least two years of basic training. We received none. Intergalactic explorers understand gravity, air pressure, and other important criteria based on decades of space knowledge. Alternatively, new novel coronavirus data is coming in real time, changing the threats, precautions, and needs dramatically. Things feel a little different when you're winging it.
Lastly, with respect to Apollo 13, space travelers have a timeline for when their experience will be over. There are mishaps, challenges and adjustments, but every well-supported journeyperson leaves Earth with an agenda (and a team back home to help keep them on track).
The pandemic, on the other hand, has no definitive end. It is unclear when a reliable vaccine will be readily available. It is also not known how long we should shelter-in-place, as pulling the trigger too early could bring another wave of illness. We are missing definitive milestones, which, Vermeulen says, would make our isolation experience easier to navigate. "When you're on a mission, the end date is always on the horizon. You can celebrate the midpoint and check off major milestones, which helps."
Also, unlike a kid pretending to be in a rocket, most of us didn't dream of one day being socially isolated for an indeterminate amount of time. "If you're ambitious and working in the field, then it is your goal in life to experience [space and the related isolation]," he says. "With the pandemic, though, nobody chose to do this."
[Editor's Note: This article was originally published on June 8th, 2020 as part of a standalone magazine called GOOD10: The Pandemic Issue. Produced as a partnership among LeapsMag, The Aspen Institute, and GOOD, the magazine is available for free online.]