When Rita Levi-Montalcini decided to become a scientist, she was determined that nothing would stand in her way. And from the beginning, that determination was put to the test. Before Levi-Montalcini became a Nobel Prize-winning neurobiologist, the first to discover and isolate a crucial chemical called Neural Growth Factor (NGF), she would have to battle both the sexism within her own family as well as the racism and fascism that was slowly engulfing her country
Levi-Montalcini was born to two loving parents in Turin, Italy at the turn of the 20th century. She and her twin sister, Paola, were the youngest of the family's four children, and Levi-Montalcini described her childhood as "filled with love and reciprocal devotion." But while her parents were loving, supportive and "highly cultured," her father refused to let his three daughters engage in any schooling beyond the basics. "He loved us and had a great respect for women," she later explained, "but he believed that a professional career would interfere with the duties of a wife and mother."
Science Under a Fascist Regime<p>Two years into her research assistant position, Levi-Montalcini was fired, along with every other "non-Aryan Italian" who held an academic or professional career, thanks to a series of antisemitic laws passed by Italy's then-leader Benito Mussolini. Forced out of her academic position, Levi-Montalcini went to Belgium for a fellowship at a neurological institute in Brussels – but then was forced back to Turin when the German army invaded.</p><p>Levi-Montalcini decided to keep researching. She and Guiseppe Levi built a makeshift lab in Levi-Montalcini's apartment, borrowing chicken eggs from local farmers and using sewing needles to dissect them. By dissecting the chicken embryos from her bedroom laboratory, she was able to see how nerve fibers formed and died. The two continued this research until they were interrupted again – this time, by British air raids. Levi-Montalcini fled to a country cottage to continue her research, and then two years later was forced into hiding when the German army invaded Italy. Levi-Montalcini and her family assumed different identities and lived with non-Jewish friends in Florence to survive the Holocaust. Despite all of this, Levi-Montalcini continued her work, dissecting chicken embryos from her hiding place until the end of the war. </p>
A Post-War Discovery<p>Several years after the war, when Levi-Montalcini was once again working at the University of Turin, a German embryologist named Viktor Hamburger invited her to Washington University in St. Louis. Hamburger was impressed by Levi-Montalcini's research with her chicken embryos, and secured an opportunity for her to continue her work in America. The invitation would "change the course of my life," Levi-Montalcini would later recall.</p><p>During her fellowship, Montalcini grew tumors in mice and then transferred them to chick embryos in order to see how it would affect the chickens. To her surprise, she noticed that introducing the tumor samples would cause nerve fibers to grow rapidly. From this, Levi-Montalcini discovered and was able to isolate a protein that she determined was able to cause this rapid growth. She later named this Nerve Growth Factor, or NGF. </p><p>From there, Levi-Montalcini and her team launched new experiments to test NGF, injecting it and repressing it to see the effect it had in a test subject's body. When the team injected NGF into embryonic mice, they observed nerve growth, as well as the mouse pups developing faster – their eyes opening earlier and their teeth coming in sooner – than the untreated group. When the team purified the NGF extract, however, it had no effect, leading the team to believe that something else in the crude extract of NGF was influencing the growth of the newborn mice. Stanley Cohen, Levi-Montalcini's colleague, identified another growth factor called EGF – epidermal growth factor – that caused the mouse pups' eyes and teeth to grow so quickly. </p><p>Levi-Montalcini continued to experiment with NGF for the next several decades at Washington University, illuminating how NGF works in our body. When Levi-Montalcini injected newborn mice with an antiserum for NGF, for example, her team found that it "almost completely deprived the animals of a sympathetic nervous system." Other experiments done by Levi-Montalcini and her colleagues helped show the role that NGF plays in other important biological processes, such as the regulation of our immune system and ovulation. <br> </p><p>"The discovery of NGF really changed the world in which we live, because now we knew that cells talk to other cells, and that they use soluble factors. It was hugely important," <a href="https://www.pnas.org/content/110/13/4873" target="_blank">said</a> Bill Mobley, Chair of the Department of Neurosciences at the University of California, San Diego School of Medicine. </p>
Her Lasting Legacy<p>After years of setbacks, Levi-Montalcini's groundbreaking work was recognized in 1986, when she was awarded the Nobel Prize in Medicine for her discovery of NGF (Cohen, her colleague who discovered EGF, shared the prize). Researchers continue to study NGF even to this day, and the continued research has been able to increase our understanding of diseases like HIV and Alzheimer's. </p><p>Levi-Montalcini never stopped researching either: In January 2012, at the age of 102, Levi-Montalcini published her last research paper in the journal PNAS, making her the oldest member of the National Academy of Science to do so. Before she died in December 2012, she encouraged other scientists who would suffer setbacks in their careers to keep pursuing their passions. "Don't fear the difficult moments," Levi-Montalcini is quoted as saying. "The best comes from them." </p>
In July 1956, a new drug hit the European market for the first time. The drug was called thalidomide – a sedative that was considered so safe it was available without a prescription.
Sedatives were in high demand in post-war Europe – but barbiturates, the most widely-used sedative at the time, caused overdoses and death when consumers took more than the recommended amount. Thalidomide, on the other hand, didn't appear to cause any side effects at all: Chemie Grünenthal, thalidomide's manufacturer, dosed laboratory rodents with over 600 times the normal dosage during clinical testing and had observed no evidence of toxicity.
The drug therefore was considered universally safe, and Grünenthal supplied thousands of doctors with samples to give to their patients. Doctors were encouraged to recommend thalidomide to their pregnant patients specifically because it was so safe, in order to relieve the nausea and insomnia associated with the first trimester of pregnancy.
Niko von Glasow, born in 1960, is a German film director and producer who was born disabled due to the side effects of thalidomide.
For 3000 years, civilizations all over the world were brutalized by smallpox, an infectious and deadly virus characterized by fever and a rash of painful, oozing sores.
Doctors had to contend with wars, floods, and language barriers to make their campaign a success.
Smallpox was merciless, killing one third of people it infected and leaving many survivors permanently pockmarked and blind. Although smallpox was more common during the 18th and 19th centuries, it was still a leading cause of death even up until the early 1950s, killing an estimated 50 million people annually.
A Primitive Cure
Sometime during the 10th century, Chinese physicians figured out that exposing people to a tiny bit of smallpox would sometimes result in a milder infection and immunity to the disease afterward (if the person survived). Desperate for a cure, people would huff powders made of smallpox scabs or insert smallpox pus into their skin, all in the hopes of getting immunity without having to get too sick. However, this method – called inoculation – didn't always work. People could still catch the full-blown disease, spread it to others, or even catch another infectious disease like syphilis in the process.
A Breakthrough Treatment
For centuries, inoculation – however imperfect – was the only protection the world had against smallpox. But in the late 18th century, an English physician named Edward Jenner created a more effective method. Jenner discovered that inoculating a person with cowpox – a much milder relative of the smallpox virus – would make that person immune to smallpox as well, but this time without the possibility of actually catching or transmitting smallpox. His breakthrough became the world's first vaccine against a contagious disease. Other researchers, like Louis Pasteur, would use these same principles to make vaccines for global killers like anthrax and rabies. Vaccination was considered a miracle, conferring all of the rewards of having gotten sick (immunity) without the risk of death or blindness.
Scaling the Cure
As vaccination became more widespread, the number of global smallpox deaths began to drop, particularly in Europe and the United States. But even as late as 1967, smallpox was still killing anywhere from 10 to 15 million people in poorer parts of the globe. The World Health Assembly (a decision-making body of the World Health Organization) decided that year to launch the first coordinated effort to eradicate smallpox from the planet completely, aiming for 80 percent vaccine coverage in every country in which the disease was endemic – a total of 33 countries.
But officials knew that eradicating smallpox would be easier said than done. Doctors had to contend with wars, floods, and language barriers to make their campaign a success. The vaccination initiative in Bangladesh proved the most challenging, due to its population density and the prevalence of the disease, writes journalist Laurie Garrett in her book, The Coming Plague.
In one instance, French physician Daniel Tarantola on assignment in Bangladesh confronted a murderous gang that was thought to be spreading smallpox throughout the countryside during their crime sprees. Without police protection, Tarantola confronted the gang and "faced down guns" in order to immunize them, protecting the villagers from repeated outbreaks.
Because not enough vaccines existed to vaccinate everyone in a given country, doctors utilized a strategy called "ring vaccination," which meant locating individual outbreaks and vaccinating all known and possible contacts to stop an outbreak at its source. Fewer than 50 percent of the population in Nigeria received a vaccine, for example, but thanks to ring vaccination, it was eradicated in that country nonetheless. Doctors worked tirelessly for the next eleven years to immunize as many people as possible.
The World Health Organization declared smallpox officially eradicated on May 8, 1980.
A Resounding Success
In November 1975, officials discovered a case of variola major — the more virulent strain of the smallpox virus — in a three-year-old Bangladeshi girl named Rahima Banu. Banu was forcibly quarantined in her family's home with armed guards until the risk of transmission had passed, while officials went door-to-door vaccinating everyone within a five-mile radius. Two years later, the last case of variola major in human history was reported in Somalia. When no new community-acquired cases appeared after that, the World Health Organization declared smallpox officially eradicated on May 8, 1980.
Because of smallpox, we now know it's possible to completely eliminate a disease. But is it likely to happen again with other diseases, like COVID-19? Some scientists aren't so sure. As dangerous as smallpox was, it had a few characteristics that made eradication possibly easier than for other diseases. Smallpox, for instance, has no animal reservoir, meaning that it could not circulate in animals and resurge in a human population at a later date. Additionally, a person who had smallpox once was guaranteed immunity from the disease thereafter — which is not the case for COVID-19.
In The Coming Plague, Japanese physician Isao Arita, who led the WHO's Smallpox Eradication Unit, admitted to routinely defying orders from the WHO, mobilizing to parts of the world without official approval and sometimes even vaccinating people against their will. "If we hadn't broken every single WHO rule many times over, we would have never defeated smallpox," Arita said. "Never."
Still, thanks to the life-saving technology of vaccines – and the tireless efforts of doctors and scientists across the globe – a once-lethal disease is now a thing of the past.