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."
Is Sex for Reproduction About to Become Extinct?
There are lots of great reasons we humans have sex. We mostly do it to pair bond, realize our primal urges, and feel good. Once in a while, we also do it to make babies. As the coming genetic revolution plays out, we'll still have sex for most of the same reasons we do today. But we'll increasingly not do it to procreate.
Protecting children from harm is one of the core responsibilities of parenting.
Most parents go to great lengths to protect their children from real and imagined harms. This begins with taking prenatal vitamins during pregnancy and extends to having children immunized and protected from exposures to various diseases and dangers. Most of us look askance for good reason at mothers who abuse controlled substances during their pregnancies or parents who choose to not immunize their children. Protecting children from harm is one of the core responsibilities of parenting.
In the United States today, up to two percent of babies are estimated to be born with rare genetic diseases caused by single gene mutations. Sickle cell disease, Tay-Sachs, and Huntington's disease are among the more well-known examples of these, but the list runs to the thousands. Many babies born with these disorders suffer terribly, some die young, and nearly all spend big chunks of their lives struggling through the medical system.
Increasingly, however, many of these single-gene mutation diseases and other chromosomal disorders like Down syndrome are being identified in non-invasive prenatal tests performed on expectant mothers at the end of their first trimester of pregnancy. Knowing the hardship that children born with these types of disorders will likely face, majorities of these women in countries around the world are choosing to terminate pregnancies once these diagnoses have been made. Whatever the justification and whatever anyone's views on the morality of abortion, these decisions are inherently excruciating.
A much smaller number of prospective mothers, however, are today getting this same information about their potential future children before their pregnancies even begin. By undergoing both in vitro fertilization (IVF) and preimplantation genetic testing (PGT), these women are able to know which of the eggs that have been surgically extracted from them and fertilized with their partner or donor's sperm will carry the dangerous mutations. The in vitro embryos with these disorders are simply not implanted in the expectant mother's womb.
It would be monstrous to assert that an existing person with a deadly disease has any less right to thrive than anyone else. But it would also be hard to make a case that parents should affirmatively choose to implant embryos carrying such a disease if given the option. If prospective parents are already today choosing not to implant certain embryos based on our preliminary understanding of disease risk, what will happen when this embryo selection is based on far more information than just a few thousand single gene mutation diseases?
Our ability and willingness to make genetic alterations to our future children will grow over time along with our knowledge and technological ability.
When the first human genome was sequenced in 2003, the race to uncover the mysteries of human genetics had only just begun. Although we still know very little about our genetics relative to the complexity of the genome and even less compared to the broader ecosystem of our biology, the progress toward greater understanding is astounding. Today, the number of single gene mutation diseases and relatively simple genetic traits that can be predicted meaningfully from genetic data alone is already significant.
In the not-distant future, this list will grow to include complex diseases and disease propensities, percentage probabilities of living a long and healthy life, and increasingly the genetic component of complex human attributes like height, IQ, and personality style. This predictive power of genetic analysis will funnel straight into our fertility clinics where prospective parents choosing embryos will be making ever more consequential decisions about the genetic components of the future lives, health, and capabilities of their children.
Our understanding of what the genes extracted from early stage pre-implanted embryos are telling us will be only one of the rocket boosters driving assisted reproduction forward. Another will be the ability to induce adult cells like skin and nucleated blood cells into stem cells and then turn those stem cells into egg progenitor cells and then ultimately eggs. This will not only eliminate the need for hormone treatments and surgery to extract human eggs but also make it easy and cheap to generate an unlimited number of eggs from a given woman.
The average woman has around fifteen eggs extracted during IVF but imagine what generating a thousand eggs will do to the range of possibilities that could be realized through pre-implantation embryo selection. Each of these thousand eggs would be the natural offspring of the two parents, but the variation between them would make it possible to choose the ones with the strongest expression of the genetic component of a particular desired trait – like those with the highest possible genetic IQ potential.
Another rocket booster will be the application of gene editing technologies like CRISPR to edit the genomes of pre-implanted embryos or of the sperm and eggs used to create them. Just this week, Chinese researchers announced they had used CRISPR to edit the CCR5 gene in the pre-implanted embryos of a pair of Chinese twins to make them immune to HIV, the first ever case of gene editing humans and a harbinger of our genetically engineered future. The astounding complexity of the human genome will put limits on our ability to safely make too many simultaneous genetic changes to human embryos, but our ability and willingness to make these types of alterations to our future children will grow over time along with our knowledge and technological ability.
With so much at stake, prospective parents will increasingly have a stark choice when determining how to conceive their children. If they go the traditional route of sex, they will experience both the benign wisdom and unfathomable cruelty of nature. If they use IVF and increasingly informed embryo selection, they will eliminate most single gene mutation diseases and likely increase their children's chances of living a longer and healthier life with more opportunity than their unenhanced peers. But the optimizing parents could also set up their children for misery if these children don't particularly enjoy what they have been optimized to become or see themselves as some type of freakish consumer product with emotions.
Conceiving though sex will come to be seen more and more like not immunizing your children is today, a perfectly natural choice that comes with a significant potential risk and expense.
But although there will be pros and cons on each side, the fight between conception through good old-fashioned sex and conception in the lab will ultimately not be fair. Differences and competition within and between societies will pressure parents and societies to adopt ever more aggressive forms of reproductive technology if they believe doing so will open possibilities and create opportunities for the next generations rather than close them.
Conception through sex will remain as useful as it has always been but lab conception will only get more advantageous. Over time, only zealots will choose to roll the dice of their future children's health and well-being rather than invest, like parents always have, in protecting their children from harm and helping optimize their life potential. Conceiving though sex will come to be seen more and more like not immunizing your children is today, a perfectly natural choice that comes with a significant potential risk and expense to yourself, your children, and your community.
As this future plays out, the genetics and assisted reproduction revolutions will raise enormous, thorny, and massively consequential questions about how we value and invest in diversity, equality, and our own essential humanity – questions we aren't remotely prepared to answer. But these revolutions are coming sooner than most of us understand or are prepared for so we had better get ready.
Because where this trail is ultimately heading goes well beyond sex and toward a fundamental transformation of our evolutionary process as a species – and that should be everybody's business.
Top Fertility Doctor: Artificially Created Sperm and Eggs "Will Become Normal" One Day
Imagine two men making a baby. Or two women. Or an infertile couple. Or an older woman whose eggs are no longer viable. None of these people could have a baby today without the help of an egg or sperm donor.
Cells scraped from the inside of your cheek could one day be manipulated to become either eggs or sperm.
But in the future, it may be possible for them to reproduce using only their own genetic material, thanks to an emerging technology called IVG, or in vitro gametogenesis.
Researchers are learning how to reprogram adult human cells like skin cells to become lab-created egg and sperm cells, which could then be joined to form an embryo. In other words, cells scraped from the inside of your cheek could one day be manipulated to become either eggs or sperm, no matter your gender or your reproductive fitness.
In 2016, Japanese scientists proved that the concept could be successfully carried out in mice. Now some experts, like Dr. John Zhang, the founder and CEO of New Hope Fertility Center in Manhattan, say it's just "a matter of time" before the method is also made to work in humans.
Such a technological tour de force would upend our most basic assumptions about human reproduction and biology. Combined with techniques like gene editing, these tools could eventually enable prospective parents to have an unprecedented level of choice and control over their children's origins. It's a wildly controversial notion, and an especially timely one now that a Chinese scientist has announced the birth of the first allegedly CRISPR-edited babies. (The claims remain unverified.)
Zhang himself is no stranger to controversy. In 2016, he stunned the world when he announced the birth of a baby conceived using the DNA of three people, a landmark procedure intended to prevent the baby from inheriting a devastating neurological disease. (Zhang went to a clinic in Mexico to carry out the procedure because it is prohibited in the U.S.) Zhang's other achievements to date include helping a 49-year-old woman have a baby using her own eggs and restoring a young woman's fertility through an ovarian tissue transplant surgery.
Zhang recently sat down with our Editor-in-Chief in his New York office overlooking Columbus Circle to discuss the fertility world's latest provocative developments. Here are his top ten insights:
Clearly [gene-editing embryos] will be beneficial to mankind, but it's a matter of how and when the work is done.
1) On a Chinese scientist's claim of creating the first CRISPR-edited babies:
I'm glad that we made a first move toward a clinical application of this technology for mankind. Somebody has to do this. Whether this was a good case or not, there is still time to find out.
Clearly it will be beneficial to mankind, but it's a matter of how and when the work is done. Like any scientific advance, it has to be done in a very responsible way.
Today's response is identical to when the world's first IVF baby was announced in 1978. The major news media didn't take it seriously and thought it was evil, wanted to keep a distance from IVF. Many countries even abandoned IVF, but today you see it is a normal practice. And it took almost 40 years [for the researchers] to win a Nobel Prize.
I think we need more time to understand how this work was done medically, ethically, and let the scientist have the opportunity to present how it was done and let a scientific journal publish the paper. Before these become available, I don't think we should start being upset, scared, or giving harsh criticism.
2) On the international outcry in response to the news:
I feel we are in scientific shock, with many thinking it came too fast, too soon. We all embrace modern technology, but when something really comes along, we fear it. In an old Chinese saying, one of the masters always dreamed of seeing the dragon, and when the dragon really came, he got scared.
Dr. John Zhang, the founder and CEO of New Hope Fertility Center in Manhattan, pictured in his office.
3) On the Western world's perception that Chinese scientists sometimes appear to discount ethics in favor of speedy breakthroughs:
I think this perception is not fair. I don't think China is very casual. It's absolutely not what people think. I don't want people to feel that this case [of CRISPR-edited babies] will mean China has less standards over how human reproduction should be performed. Just because this happened, it doesn't mean in China you can do anything you want.
As far as the regulation of IVF clinics, China is probably the most strictly regulated of any country I know in this world.
4) On China's first public opinion poll gauging attitudes toward gene-edited babies, indicating that more than 60 percent of survey respondents supported using the technology to prevent inherited diseases, but not to enhance traits:
There is a sharp contrast between the general public and the professional world. Being a working health professional and an advocate of scientists working in this field, it is very important to be ethically responsible for what we are doing, but my own feeling is that from time to time we may not take into consideration what the patient needs.
5) On how the three-parent baby is doing today, several years after his birth:
No news is good news.
6) On the potentially game-changing research to develop artificial sperm and eggs:
First of all I think that anything that's technically possible, as long as you are not harmful to other people, to other societies, as long as you do it responsibly, and this is a legitimate desire, I think eventually it will become reality.
My research for now is really to try to overcome the very next obstacle in our field, which is how to let a lady age 44 or older have a baby with her own genetic material.
Practically 99 percent of women over age 43 will never make a baby on their own. And after age 47, we usually don't offer donor egg IVF anymore.
But with improved longevity, and quality of life, the lifespan of females continues to increase. In Japan, the average for females is about 89 years old. So for more than half of your life, you will not be able to produce a baby, which is quite significant in the animal kingdom. In most of the animal kingdom, their reproductive life is very much the same as their life, but then you can argue in the animal kingdom unlike a human being, it doesn't take such a long time for them to contribute to the society because once you know how to hunt and look for food, you're done.
"I think this will become a major ethical debate: whether we should let an older lady have a baby at a very late state of her life."
But humans are different. You need to go to college, get certain skills. It takes 20 years to really bring a human being up to become useful to society. That's why the mom and dad are not supposed to have the same reproductive life equal to their real life.
I think this will become a major ethical debate: whether we should let an older lady have a baby at a very late state of her life and leave the future generation in a very vulnerable situation in which they may lack warm caring, proper guidance, and proper education.
7) On using artificial gametes to grant more reproductive choices to gays and lesbians:
I think it is totally possible to have two sperm make a baby, and two eggs make babies.
If we have two guys, one guy to produce eggs, or two girls, one would have to become sperm. Basically you are creating artificial gametes or converting with gametes from sperm to become egg or egg to become a sperm. Which may not necessarily be very difficult. The key is to be able to do nuclear reprogramming.
So why can two sperm not make offspring now? You get exactly half of your genes from each parent. The genes have their own imprinting that say "made in mom," "made in dad." The two sperm would say "made in dad," "made in dad." If I can erase the "made in dad," and say "made in mom," then these sperm can make offspring.
8) On how close science is to creating artificial gametes for clinical use in pregnancies:
It's very hard to say until we accomplish it. It could be very quick. It could be it takes a long time. I don't want to speculate.
"I think these technologies are the solid foundation just like when we designed the computer -- we never thought a computer would become the iPhone."
9) On whether there should be ethical red lines drawn by authorities or whether the decisions should be left to patients and scientists:
I think we cannot believe a hundred percent in the scientist and the patient but it should not be 100 percent authority. It should be coming from the whole of society.
10) On his expectations for the future:
We are living in a very exciting world. I think that all these technologies can really change the way of mankind and also are not just for baby-making. The research, the experience, the mechanism we learn from these technologies, they will shine some great lights into our long-held dream of being a healthy population that is cancer-free and lives a long life, let's say 120 years.
I think these technologies are the solid foundation just like when we designed the computer -- we never thought a computer would become the iPhone. Imagine making a computer 30 years ago, that this little chip will change your life.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.