The Scientist Behind the Pap Smear Saved Countless Women from Cervical Cancer
For decades, women around the world have made the annual pilgrimage to their doctor for the dreaded but potentially life-saving Papanicolaou test, a gynecological exam to screen for cervical cancer named for Georgios Papanicolaou, the Greek immigrant who developed it.
The Pap smear, as it is commonly known, is credited for reducing cervical cancer mortality by 70% since the 1960s; the American Cancer Society (ACS) still ranks the Pap as the most successful screening test for preventing serious malignancies. Nonetheless, the agency, as well as other medical panels, including the US Preventive Services Task Force and the American College of Obstetrics and Gynecology are making a strong push to replace the Pap with the more sensitive high-risk HPV screening test for the human papillomavirus virus, which causes nearly all cases of cervical cancer.
So, how was the Pap developed and how did it become the gold standard of cervical cancer detection for more than 60 years?
Born on May 13, 1883, on the island of Euboea, Greece, Georgios Papanicolaou attended the University of Athens where he majored in music and the humanities before earning his medical degree in 1904 and PhD from the University of Munich six years later. In Europe, Papanicolaou was an assistant military surgeon during the Balkan War, a psychologist for an expedition of the Oceanographic Institute of Monaco and a caregiver for leprosy patients.
When he and his wife, Andromache Mavroyenous (Mary), arrived at Ellis Island on October 19, 1913, the young couple had scarcely more than the $250 minimum required to immigrate, spoke no English and had no job prospects. They worked a series of menial jobs--department store sales clerk, rug salesman, newspaper clerk, restaurant violinist--before Papanicolaou landed a position as an anatomy assistant at Cornell University and Mary was hired as his lab assistant, an arrangement that would last for the next 50 years.
Papanikolaou would later say the discovery "was one of the greatest thrills I ever experienced during my scientific career."
In his early research, Papanikolaou used guinea pigs to prove that gender is determined by the X and Y chromosomes. Using a pediatric nasal speculum, he collected and microscopically examined vaginal secretions of guinea pigs, which revealed distinct cell changes connected to the menstrual cycle. He moved on to study reproductive patterns in humans, beginning with his faithful wife, Mary, who not only endured his almost-daily cervical exams for decades, but also recruited friends as early research participants.
Writing in the medical journal Growth in 1920, the scientist outlined his theory that a microscopic smear of vaginal fluid could detect the presence of cancer cells in the uterus. Papanikolaou would later say the discovery "was one of the greatest thrills I ever experienced during my scientific career."
At this time, cervical cancer was the number one cancer killer of American women but physicians were skeptical of these new findings. They continued to rely on biopsy and curettage to diagnose and treat the disease until Papanicolaou's discovery was published in American Journal of Obstetrics and Gynecology. An inexpensive, easy-to-perform test that could detect cervical cancer, precancerous dysplasia and other cytological diseases was a sea change. Between 1975 and 2001, the cervical cancer rate was cut in half.
Papanicolaou became Emeritus Professor at Cornell University Medical College and received numerous awards, including the Albert Lasker Award for Clinical Medical Research and the Medal of Honor from the American Cancer Society. His image was featured on the Greek currency and the US Post Office issued a commemorative stamp in his honor. But international acclaim didn't lead to a more relaxed schedule. The researcher continued to work seven days a week and refused to take vacations.
After nearly 50 years, Papanicolaou left Cornell to head and develop the Cancer Institute of Miami. He died of a heart attack on February 19, 1962, just three months after his arrival. Mary continued to work in the renamed Papanicolaou Cancer Research Institute until her death 20 years later.
The annual pap smear was originally tied to renewing a birth control prescription. Canada began recommending Pap exams every three years in 1978. The United States followed suit in 2012, noting that it takes many years for cervical cancer to develop. In September 2020, the American Cancer Society recommended delaying the first gynecological pelvic exam until age 25 and replacing the Pap test completely with the more accurate human papillomavirus (HPV) test every five years as the technology becomes more widely available.
Not everyone agrees that it's time to do away with this proven screening method, though. The incidence rate of cervical cancer among Hispanic women is 28% higher than for white women, and Black women are more likely to die of cervical cancer than any other racial or ethnicities.
Whether the Pap is administered every year, every three years or not at all, Papanicolaou will always be known as the medical hero who saved countless women who would otherwise have succumbed to cervical cancer.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five:
- Kids stressing you out? They could be protecting your health.
- A new device unlocks the heart's secrets
- Super-ager gene transplants
- Surgeons could 3D print your organs before operations
- A skull cap looks into the brain like an fMRI
This article originally appeared in One Health/One Planet, a single-issue magazine that explores how climate change and other environmental shifts are making us more vulnerable to infectious diseases by land and by sea - and how scientists are working on solutions.
On a warm summer day, forests, meadows, and riverbanks should be abuzz with insects—from butterflies to beetles and bees. But bugs aren’t as abundant as they used to be, and that’s not a plus for people and the planet, scientists say. The declining numbers of insects, coupled with climate change, can have devastating effects for people in more ways than one. “Insects have been around for a very long time and can live well without humans, but humans cannot live without insects and the many services they provide to us,” says Philipp Lehmann, a researcher in the Department of Zoology at Stockholm University in Sweden. Their decline is not just bad, Lehmann adds. “It’s devastating news for humans.
”Insects and other invertebrates are the most diverse organisms on the planet. They fill most niches in terrestrial and aquatic environments and drive ecosystem functions. Many insects are also economically vital because they pollinate crops that humans depend on for food, including cereals, vegetables, fruits, and nuts. A paper published in PNAS notes that insects alone are worth more than $70 billion a year to the U.S. economy. In places where pollinators like honeybees are in decline, farmers now buy them from rearing facilities at steep prices rather than relying on “Mother Nature.”
And because many insects serve as food for other species—bats, birds and freshwater fish—they’re an integral part of the ecosystem’s food chain. “If you like to eat good food, you should thank an insect,” says Scott Hoffman Black, an ecologist and executive director of the Xerces Society for Invertebrate Conservation in Portland, Oregon. “And if you like birds in your trees and fish in your streams, you should be concerned with insect conservation.”
Deforestation, urbanization, and agricultural spread have eaten away at large swaths of insect habitat. The increasingly poorly controlled use of insecticides, which harms unintended species, and the proliferation of invasive insect species that disrupt native ecosystems compound the problem.
“There is not a single reason why insects are in decline,” says Jessica L. Ware, associate curator in the Division of Invertebrate Zoology at the American Museum of Natural History in New York, and president of the Entomological Society of America. “There are over one million described insect species, occupying different niches and responding to environmental stressors in different ways.”
Jessica Ware, an entomologist at the American Museum of Natural History, is using DNA methods to monitor insects.
In addition to habitat loss fueling the decline in insect populations, the other “major drivers” Ware identified are invasive species, climate change, pollution, and fluctuating levels of nitrogen, which play a major role in the lifecycle of plants, some of which serve as insect habitants and others as their food. “The causes of world insect population declines are, unfortunately, very easy to link to human activities,” Lehmann says.
Climate change will undoubtedly make the problem worse. “As temperatures start to rise, it can essentially make it too hot for some insects to survive,” says Emily McDermott, an assistant professor in the Department of Entomology and Plant Pathology at the University of Arkansas. “Conversely in other areas, it could potentially also allow other insects to expand their ranges.”
Without Pollinators Humans Will Starve
We may not think much of our planet’s getting warmer by only one degree Celsius, but it can spell catastrophe for many insects, plants, and animals, because it’s often accompanied by less rainfall. “Changes in precipitation patterns will have cascading consequences across the tree of life,” says David Wagner, a professor of ecology and evolutionary biology at the University of Connecticut. Insects, in particular, are “very vulnerable” because “they’re small and susceptible to drying.”
For instance, droughts have put the monarch butterfly at risk of being unable to find nectar to “recharge its engine” as it migrates from Canada and New England to Mexico for winter, where it enters a hibernation state until it journeys back in the spring. “The monarch is an iconic and a much-loved insect,” whose migration “is imperiled by climate change,” Wagner says.
Warming and drying trends in the Western United States are perhaps having an even more severe impact on insects than in the eastern region. As a result, “we are seeing fewer individual butterflies per year,” says Matt Forister, a professor of insect ecology at the University of Nevada, Reno.
There are hundreds of butterfly species in the United States and thousands in the world. They are pollinators and can serve as good indicators of other species’ health. “Although butterflies are only one group among many important pollinators, in general we assume that what’s bad for butterflies is probably bad for other insects,” says Forister, whose research focuses on butterflies. Climate change and habitat destruction are wreaking havoc on butterflies as well as plants, leading to a further indirect effect on caterpillars and butterflies.
Different insect species have different levels of sensitivity to environmental changes. For example, one-half of the bumblebee species in the United States are showing declines, whereas the other half are not, says Christina Grozinger, a professor of entomology at the Pennsylvania State University. Some species of bumble bees are even increasing in their range, seemingly resilient to environmental changes. But other pollinators are dwindling to the point that farmers have to buy from the rearing facilities, which is the case for the California almond industry. “This is a massive cost to the farmer, which could be provided for free, in case the local habitats supported these pollinators,” Lehmann says.
For bees and other insects, climate change can harm the plants they depend on for survival or have a negative impact on the insects directly. Overly rainy and hot conditions may limit flowering in plants or reduce the ability of a pollinator to forage and feed, which then decreases their reproductive success, resulting in dwindling populations, Grozinger explains.
“Nutritional deprivation can also make pollinators more sensitive to viruses and parasites and therefore cause disease spread,” she says. “There are many ways that climate change can reduce our pollinator populations and make it more difficult to grow the many fruit, vegetable and nut crops that depend on pollinators.”
Disease-Causing Insects Can Bring More Outbreaks
While some much-needed insects are declining, certain disease-causing species may be spreading and proliferating, which is another reason for human concern. Many mosquito types spread malaria, Zika virus, West Nile virus, and a brain infection called equine encephalitis, along with other diseases as well as heartworms in dogs, says Michael Sabourin, president of the Vermont Entomological Society. An animal health specialist for the state, Sabourin conducts vector surveys that identify ticks and mosquitoes.
Scientists refer to disease-carrying insects as vector species and, while there’s a limited number of them, many of these infections can be deadly. Fleas were a well-known vector for the bubonic plague, while kissing bugs are a vector for Chagas disease, a potentially life-threatening parasitic illness in humans, dogs, and other mammals, Sabourin says.
As the planet heats up, some of the creepy crawlers are able to survive milder winters or move up north. Warmer temperatures and a shorter snow season have spawned an increasing abundance of ticks in Maine, including the blacklegged tick (Ixodes scapularis), known to transmit Lyme disease, says Sean Birkel, an assistant professor in the Climate Change Institute and Cooperative Extension at the University of Maine.
Coupled with more frequent and heavier precipitation, rising temperatures bring a longer warm season that can also lead to a longer period of mosquito activity. “While other factors may be at play, climate change affects important underlying conditions that can, in turn, facilitate the spread of vector-borne disease,” Birkel says.
For example, if mosquitoes are finding fewer of their preferred food sources, they may bite humans more. Both male and female mosquitoes feed on sugar as part of their normal behavior, but if they aren’t eating their fill, they may become more bloodthirsty. One recent paper found that sugar-deprived Anopheles gambiae females go for larger blood meals to stay in good health and lay eggs. “More blood meals equals more chances to pick up and transmit a pathogen,” McDermott says, He adds that climate change could reduce the number of available plants to feed on. And while most mosquitoes are “generalist sugar-feeders” meaning that they will likely find alternatives, losing their favorite plants can make them hungrier for blood
Similar to the effect of losing plants, mosquitoes may get turned onto people if they lose their favorite animal species. For example, some studies found that Culex pipiens mosquitoes that transmit the West Nile virus feed primarily on birds in summer. But that changes in the fall, at least in some places. Because there are fewer birds around, C. pipiens switch to mammals, including humans. And if some disease-carrying insect species proliferate or increase their ranges, that increases chances for human infection, says McDermott. “A larger concern is that climate change could increase vector population sizes, making it more likely that people or animals would be bitten by an infected insect.”
Science Can Help Bring Back the Buzz
To help friendly insects thrive and keep the foes in check, scientists need better ways of trapping, counting, and monitoring insects. It’s not an easy job, but artificial intelligence and molecular methods can help. Ware’s lab uses various environmental DNA methods to monitor freshwater habitats. Molecular technologies hold much promise. The so-called DNA barcodes, in which species are identified using a short string of their genes, can now be used to identify birds, bees, moths and other creatures, and should be used on a larger scale, says Wagner, the University of Connecticut professor. “One day, something akin to Star Trek’s tricorder will soon be on sale down at the local science store.”
Scientists are also deploying artificial intelligence, or AI, to identify insects in agricultural systems and north latitudes where there are fewer bugs, Wagner says. For instance, some automated traps already use the wingbeat frequencies of mosquitoes to distinguish the harmless ones from the disease-carriers. But new technology and software are needed to further expand detection based on vision, sound, and odors.
“Because of their ubiquity, enormity of numbers, and seemingly boundless diversity, we desperately need to develop molecular and AI technologies that will allow us to automate sampling and identification,” says Wagner. “That would accelerate our ability to track insect populations, alert us to the presence of new disease vectors, exotic pest introductions, and unexpected declines.”