Polio (commonly known as polio) is the second disease after smallpox that is expected to be eradicated by humans, however, some worrying developments have emerged so far this year, with imported wild poliovirus re-detected in Malawi and Mozambique in Africa after being designated polio-free by the World Health Organization in 2020, and vaccine-derived poliovirus in countries that have long been polio-eliminated such as the United Kingdom, the United States and Israel. In September, the United Kingdom and the United States were added to the list of polio outbreak countries by the World Health Organization.
On World Polio Day on 24 October, Aidan O'Leary, director of the World Health Organization's polio eradication programme, said he expected to stop polio transmission by 2023 and polio eradicate by 2026.
A research assistant at Queens College in New York, USA, prepares for a PCR response for polio on August 25, 2022.
Polio mainly affects children, and when the global polio eradication effort began in 1988, there were about 350,000 cases of wild-type poliovirus infection each year, and the virus became a nightmare for countless families: patients infected with the virus invaded the nervous system within hours, causing total paralysis; The hospital is full of "iron lungs", and many patients will not be able to live without this big machine for the rest of their lives.
How was this terrible infectious disease discovered and "eliminated" today? This time, will it really "make a comeback"?
Text | Han Mingyue PhD student in the history of science and technology at Peking University
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1 An ancient virus that has coexisted with humans to this day
The coexistence of poliovirus with humans may be as old as human history. However, there are few early records of it, and it is generally believed that the earliest surviving record of polio appeared on an ancient Egyptian stele in the 14th century BC. The tablet is carved with the figure of a priest leaning on crutches, one foot with a horseshoe-shaped deformity, and an unusually slender leg, typical of polio.
An ancient Egyptian stele created around the 14th century BC. It is now in the Carlsberg Museum of Sculpture and Art, Copenhagen, Denmark.
In addition, an old man on crutches depicted on an Etruscan (ancient central Italy) vase from about the 5th century BC, with obvious high spinal deformities and muscle wasting, may also be due to polio.
Vase from the 5th century BC. It is now in the Etruscan Museum in Rome, Italy.
In 1789, the British surgeon and pharmacist Michael Underwood (1736-1820) first described the clinical symptoms of polio (known as "lower limb weakness") in a treatise on childhood diseases, "Debility of the Lower Extremities". Underwood also made important contributions to pediatric medicine by describing a variety of childhood diseases for the first time.
Debility of the Lower Extremities, published in 1789. Digital download from Wellcome Library
In 1840, the German orthopedic surgeon Jacob von Heine (1800-1879) published the first medical report on polio, which was the first time the disease was recognized as a clinical entity. In 1890, Swedish pediatrician Karl Oskar Medin (1847-1927) first conducted an empirical study of polio and described the epidemic features of the disease. In honor of Heine and Medin, polio was once known as Heine-Medin disease, and bronze busts of the two doctors are also housed in the Polio Hall of Fame.
Heine on the left and Meidin on the right, their bronze statue in the Polio Hall of Fame.
Later studies have found that polio is an intestinal infection in which the virus is transmitted mainly through the fecal-oral route, but direct oral-oral transmission is less likely. Faecal-oral transmission can occur when exposed to contaminated food or water.
The poliovirus enters the body through the mouth, travels down the digestive tract, and eventually is excreted in the stool. Although it proliferates in small amounts in the lymph nodes of the throat and tonsils, it really multiplies in the small intestine. In most cases, the infection is mild, with initial symptoms including fever, fatigue, headache, vomiting, neck stiffness and pain in the limbs. Rarely, the virus invades the brainstem and central nervous system through the bloodstream, destroying nerve cells (or motor neurons) that stimulate muscle fiber contraction.
In the worst case, polio can cause irreversible paralysis (usually in the legs). The death cases are mainly due to paralysis of the respiratory muscles and severe damage to the brainstem (or medulla oblongata).
2 Polio epidemic
Although polio has a long history with humans, it has been endemic for a long time.
In the 1930s, there were several small polio epidemics in England, the United States and the Atlantic island of St. Helena (part of the United Kingdom). In the late 19th and early 20th centuries, epidemics with wider coverage and greater numbers of people occurred in Scandinavia in northern Europe and in Massachusetts and Vermont in the United States.
Before the undulating epidemics passed, one of the worst polio epidemics in history broke out in the United States. Between 1916 and 1917, there were more than 27,000 cases of polio in the United States, killing more than 6,000 people. In New York City alone, there have been more than 9,000 cases of polio and about 2,400 deaths, almost all of them children under the age of five. At the time, the entire United States was surrounded by great panic, and the virus seemed to only hit children, and the consequences were severe. Some children are disabled for life, and many survivors can only spend the rest of their lives in the "iron lung", most likely very short. [Note: "Iron lung" was a device used at that time to help patients with muscle atrophy breathe]
"Iron lung" used in the 60s of the 20th century. Source: CDC Public Health Image Library
Although in 1916, Simon Flexner (1863-1946), then director of the nascent Rockefeller Institute for Medical Research, had observed the poliovirus under the microscope — "countless beating bright spots, no definite size and shape," research on polio was slow, with no specific treatment, no vaccine, and even unclear how it spread.
At that time, the spread of poliovirus and its severe consequences increased people's fears of the virus.
Poliovirus particles observed under an electron microscope after 1% uranyl acetate staining. Source: Boublik, M., & Drzeniek, R. (1977). Structural subunits of poliovirus particles by electron microscopy. Journal of General Virology, 37(1), 127-134.
In order to control the spread of the disease, on the one hand, the government isolates the sick people and the affected areas in accordance with the usual methods for treating the disease:
barricades to prohibit vehicles carrying children under the age of 16 from entering the city;
Hospitals receiving children with polio are segregated, and "lame" children are forcibly transferred to isolation hospitals; All public places are closed;
exile or killing of cats and dogs suspected of carrying the virus;
Spray disinfectant in the city, etc.
On the other hand, tropical medicine in the late 19th and early 20th centuries confirmed that common mosquitoes, lice, fleas and flies in life can spread diseases, and polio and cholera, typhoid fever, etc. are the main diseases in summer, so polio was once considered a "dirty disease", and maintaining the cleanliness of the living environment and personal hygiene became the top priority of residents:
City sanitation commissioners scrubbed streets with lime water to force homeowners to clean up rubbish around their homes;
The lid of the trash can is sealed, and the house is hung with a curtain to prevent flies from flying in;
Soap became a necessity of life, second only to bread and butter;
"Polio Instructions" appear in the news, in mailboxes and in shop windows, with the words "Please pay special attention to personal hygiene, drink the cleanest milk and water, do not let flies near food, do not swim in contaminated water"...
In 1950, after a polio outbreak in Virginia, Wyth County warned visitors not to stop here. Translation of the tagline: "Information for visitors: There are polio outbreaks in Wytheville and Wyth County. If you do not stop here on this tour, we welcome you to visit again next holiday. ”
But it turns out that the epidemic is not a "dirty disease" or a "disease of the poor" – the virus attacks children equally, rich or poor, regardless of skin color, rural and urban. And, because of improved sanitation, children are less likely to be exposed to pathogenic microorganisms at an early age. Specific to the impact on polio infection, infections that occur in early childhood tend to be mild, and antibodies left by the mother provide temporary protection; If the chance of forming antibodies at an early age is reduced, the symptoms of infection in adolescence are more severe.
By 1950, the peak age of onset of paralytic poliomyelitis in the United States had shifted from infants to children aged 5-9 years, with about one-third of cases occurring over the age of 15. [Note: In the 20s and 50s of the 20th century, polio epidemics occurred regularly in the United States and other industrialized countries, mainly in the summer. At the same time, paralysis and mortality from polio infection are increasing, with 57,628 infections reported in the 1952 polio epidemic in the United States, of which 21,269 (about 37 percent) had mild to disabling paralysis.
3 The paralyzed president and "one dime per man"
In 1921, 39-year-old Franklin D. Roosevelt contracted polio, and he was the hottest star in the Republican Party at the time. In the summer of 1921, Roosevelt and his family were vacationing on Campobello Island in southern Canada, perhaps exhausted by a few days of swimming and boating, and feeling paralyzed when he suddenly fell from his boat into the icy waters of the Bay of Fundy. In the days that followed, his legs became weaker and weaker, his body ached, his fever persisted, and his skin became so sensitive that he could not even tolerate the gentle rubbing of his pajamas. Soon, Roosevelt's legs could not support him to stand, and he was completely incapacitated from the waist down. Under the diagnosis of Robert Lovett, a professor at Harvard University and a polio specialist, Roosevelt was diagnosed with polio. Doctors recommend that to fight polio, it is necessary to maintain good emotional and physical health and have a healthy immune system.
For three years after his illness, Roosevelt devoted himself to physical rehabilitation. He goes to the park near his home to swim several times a week, moving his lower limbs as much as possible supported by the buoyancy of the water. The swimming site became a spa in Georgia because he heard that the mineral-rich water had miraculously cured a young man who was also suffering from polio.
In October 1925, Roosevelt swam in a swimming pool in Hot Springs, Georgia. Photo courtesy of Franklin D. Roosevelt Presidential Library and Museum
Although swimming and hot springs did not get Roosevelt back on his feet, he not only became physically stronger, but also remained positive and optimistic during his rehab. With the support of his family, Roosevelt returned to politics in 1924 and was elected governor of New York in 1928 and president of the United States in 1933. Since then, he has served four consecutive terms as president, leading the United States out of economic crisis through World War II until he died of a cerebral hemorrhage in 1945.
Roosevelt rarely showed himself as a wheelchair to the public, even at home, using a dining chair on wheels. He doesn't want his disability to attract much attention, but the physical discomfort and pain he feels is real, and he often speaks publicly about the difficulties faced by polio patients.
To raise money to help polio patients, Roosevelt used his birthday to host a series of charity balls to raise money for the fight against polio. Under the slogan "Dance Together, Make Others Stand Up," more than 6,000 charity balls were held across the United States, and the first dance alone raised more than $1 million.
In addition to funding the treatment of polio patients, a small portion of the funds raised is allocated to support polio vaccine research projects.
In 1938, Roosevelt announced that the committee spawned from the birthday ball would be renamed the National Polio Foundation, with the primary goal of finding a cure for polio while providing patients with the best treatment available. When the foundation was launched, it introduced a new tagline, "March of Dimes" — a dime that everyone could send to the president of the White House.
After the initiative was released on the radio, it received a very enthusiastic response. Why not donate a dime to charity and get the chance to fight polio side by side with the president? Since then, a dime has become a symbol of the fight against polio. In January 1946, after Roosevelt's death, the United States issued a dime coin for Roosevelt's head to commemorate the president's contribution to the fight against polio.
The first from the left is a Roosevelt dime issued in 1946, and since then the dime in the United States has a Roosevelt head on the obverse; the second is a propaganda poster for the 1955 "One Dime per Man" campaign; The third is a photo of Mary Kosloski, a girl on a propaganda poster, with Randy Kerr, the first to be vaccinated against Salk in the spring of 1954. The two of them represent the two goals of the One Man, One Dime movement: healing and healing.
4 Machine "Iron Lung" with Sister Kenny
For a long time after the polio epidemic, there was no specific treatment for the disease, and many people chose to soak in hot springs, massage and other ways to relieve their pain. But for patients with severe paralysis, many have paralyzed weakness of the respiratory muscles and respiratory tract, that is, difficulty breathing and swallowing on their own, which is fatal for the patient.
In 1928, Harvard School of Public Health professors Philip Drinker (1894–1972) and Louis Agassiz Shaw Jr. (1886-1940) built the first negative pressure ventilator, which works by placing the patient's body below the head in a sealed box, and by changing the air pressure in the box, the chest cavity expands or contracts, thereby helping the patient breathe. In October 1928, the "iron lung" was first used on an 8-year-old girl with respiratory failure due to polio, and her symptoms were immediately relieved when the machine was turned on. The principle of "iron lung" assisted breathing is: when inhaling, the gas in the sealed box is withdrawn, the patient's chest cavity is dilated, and the gas is inhaled into the lungs; On exhalation, the air in the sealed box is compressed, the patient's chest cavity is also retracted, and the gas is pressed out of the lungs.
Since then, the "iron lung" has been modified several times, and some have been added with small windows, allowing doctors and nurses to observe patients through the windows and reach in to make adjustments for patients. Although the "iron lung" was originally created only as a "stopgap measure" to help patients in emergencies and wait for patients to resume spontaneous breathing, its inventor Derrinke never considered it as a long-term device. But in the polio epidemic era, hospitals are full of rows of "iron lungs", and many patients may have to spend their lives with this big machine.
The "Iron Lung" ward at Haynes Memorial Hospital in Boston, Massachusetts, 1955. Image credit: National Museum of American History
The patient lay motionless on his back in the cold "iron lung", and the nurse occasionally came to check on the situation. A family member of a patient who had used the "iron lung" for a long time recalled, "At night, the patient lying in the "iron lung" was disturbed by all kinds of noisy sounds... The 'rattling' sound of the patient's breath, the 'creak' of the rubber sole rubbing when the nurse walks around the corridor, the 'stinging' sound when the nurse pushes the infusion stand away... Souls that cannot sleep can only engage in intense self-torture." The head of respirators at the Polio Fund also said, "The invention of the 'iron lung' was originally intended to benefit mankind, but seeing patients who have been using respirators for a long time so miserable, caregivers will inevitably begin to reflect... In fact, such patients can't do anything..." But it is undeniable that the "iron lung" has saved countless lives and countless families.
In the 30s of the 20th century, a method of splint fixation was popular in the United States: the patient's body was thoroughly immobilized with a wooden splint and plaster to prevent muscle and joint deformation. One polio expert disputed this, but he also knew that "it takes a lot of energy to prove that this method is ineffective or even harmful." Sister Elizabeth Kenny (1880-1952), a nun from Australia, challenged this, and she also brought humanist care. In the early 2030s, Kenny was caring for a girl maimed by polio in Australia, and with her help, the little girl got back on her feet and returned to a normal life. Since then, Kenny has helped several polio children in succession.
She has no medical training, but years of caring for patients have given her a keen intuition for the anatomy of the human body. In her eyes, polio-induced polio is more like a muscle spasm, and the key to treatment is to relax the affected muscles, and the immobilization of splints and casts only exacerbates the disability. Her approach is to relieve muscle spasms with warm compresses and gentle exercises, so that patients can relearn to use "unfamiliar" muscles, build image memories through repeated practice and optimism, and master movements that were once familiar.
Sister Kenny examines a polio child in 1942.
"Remind the brain not to forget how to walk." This is Nurse Kenny's secret to treating polio patients. Although Kenny's methods have been ridiculed and criticized by many, many of the patients she has cared for have made significant progress, with some children able to walk again and others able to get back up with crutches. "At that time, many children had to splint at the age of three, and for two years, the child himself forgot about the existence of the limb," and "if my child had polio, I would want him to accept Kenny's methods." ”
The machine "iron lung," Kenny's humanist approach, the fixation of splints and casts, and Roosevelt's favored swimming in hot springs have made many explorations to ease the suffering of polio patients and seek to restore bodily functions. What really brought humanity out of the polio nightmare was the invention of the vaccine.
5 Show the way to vaccine preparation
Scientists have been figuring out how to make a vaccine ever since Karl Landsteiner (1868-1943) confirmed in 1909 that the causative agent of polio was a virus.
In the 2030s, two types of polio vaccines emerged:
One is the Parker-Brody vaccine, funded by the former American Polio Foundation (the birthday prom committee mentioned above), developed by bacteriologists William Parker and Maurice Brody. They used monkey brains to culture the poliovirus and then inactivated formalin, but the vaccine prepared in this way led to allergic encephalitis.
The other was the vaccine by dermatologist John Kollmer (1886-1962). He collected live polio virus and "attenuated" it in castor oil and castor protein. The vaccine prepared in this way vaccinated about 20,000 children and caused the deaths of nine children. Both vaccines were initially widely publicized by the media as a dawn of polio ending, but both ended in fiasco.
However, the failure of these two vaccines did not discourage scientists: first, Brody and Colmer's efforts to prepare vaccines represented the epoch of the vaccine production industry at that time; Secondly, there is no drug against the virus, and we can only hope that the vaccine stimulates the immune system to produce effective antibodies that can help the body resist when the virus attacks the body.
In 1949, David Bodian (1910-1992) published a paper describing the study of "Identification of Poliovirus Types", showing that there are three types of polioviruses in existence, the main difference of which is the capsid protein. All three viruses are highly virulent and can cause polio. The results of this laboratory study were validated in subsequent classification projects: type I virus covered 82% of the virus strains, type II accounted for 10%, and type III accounted for 8%. Determining the type of virus is equivalent to the "enemy" that needs to be fought is already very specific, which undoubtedly makes the preparation of the vaccine a big step forward.
Another serendipitous discovery led poliovirus research out of a dead end, where researchers once thought poliovirus grew only in neural tissue. Since the discovery of the causative agent of polio, the Rockefeller Institute of Medicine has been at the forefront of studying polioviruses.
But the polio strain they used is a highly neurotropic strain, and scientists at the Rockefeller Institute concluded that poliovirus could not survive in other tissues. In addition, the head of the Rockefeller Institute at the time was Flexner, an authoritative expert on polio. Authoritative experts in the most prestigious research institutions, under the double "guarantee", almost all of them accept the conclusion that poliovirus only grows in neural tissue.
As a result, scientists struggled to grow viruses in neural tissue, and research progressed slowly.
During a culture of varicella, John Enders (1897-1985) and his partners tried to inoculate type II poliovirus on excess muscle tissue culture media, and it was shown that poliovirus could multiply in muscle tissue. Since then, they have conducted several experiments that have finally proved that all three types of poliovirus can multiply in different human tissues, not just neural tissue.
[Note: Since the 20s of the 20th century, penicillin and streptomycin have been used in viral culture, which effectively prevents bacterial contamination and prolongs the time of virus growth. 】
In 1949, Enders published their findings. The discovery, which earned Enders and two colleagues the 1954 Nobel Prize in Physiology or Medicine, also charted the way to the preparation of polio vaccines.
By the 50s of the 20th century, research had confirmed that there are three types of poliovirus, all of which can be cultured in non-neurological tissue. At this point, polio vaccine research has entered a period of rapid development.
6 With the rollout of vaccines, polio is under control
In 1949, the National Polio Foundation hired Jonas Edward Salk (1914-1995) to lead the development of the polio vaccine. Most institutional experts at the time preferred the preparation of live vaccines, including Salk's strongest competitor, Albert Sabin (1906-1993). Previously, Salk had successfully prepared an inactivated flu vaccine and vaccinated millions of US troops. So he believes that an inactivated vaccine is feasible and insists on developing an inactivated polio vaccine.
In 1952, Salk administered his inactivated vaccine to 43 children at the D.T. Watson Home for Disabled Children; later vaccinated a school child with intellectual retardation. In early 1953, Salk published the vaccination in the Journal of the American Medical Association, causing an uproar among his peers; During the same period, he introduced his work on a television talk show, which attracted strong public attention. In April, Salk vaccinated his wife and three sons with inactivated polio vaccine.
In 1954, the "largest public health trial in history" was conducted in the United States, and more than 400,000 children were vaccinated against Salk. In April 1995, the results of the trial were announced, the vaccine was proven to be effective against polio, and the Salk vaccine was approved.
Raw statistics for the trial. Source: They Should Walk.
But not long after the results of the test were announced, the "Carter Incident" occurred. More than 200,000 vaccines prepared by Berkeley Carter's lab were contaminated with uninactivated viruses, and the injection of contaminated vaccines caused 70,000 infections, 164 cases of severe paralysis and 10 deaths. After the Carter incident, people's trust in the Salk vaccine has declined, and the universal vaccination program has slowed down. This episode gave the Sabine vaccine the opportunity to "come later".
[Note: In fact, between 1955 and 1961, about 100 million people in the United States were vaccinated against Salk; In 1961, there were 1,312 cases of polio infection in the United States, a 97% drop from 1952, which cannot but be attributed to the Salk vaccine. 】
Salk at the hospital's virus research lab in Pittsburgh, USA.
Since 1957, Sabin has successfully carried out clinical trials of oral live attenuated vaccines in the Soviet Union and other places. In 1961, the Sabin vaccine received marketing authorization in the United States. Because the Sabin vaccine was taken orally rather than injected, its convenience and efficiency quickly made it mainstream in the world and gradually replaced the Salk vaccine.
In the 50s of the 20th century, a schoolchild in Baltimore, Maryland, USA, received a polio vaccine.
With the rollout of the vaccine, polio was brought under control. After 1979, wild poliovirus was eradicated in the United States.
In 1988, the World Health Assembly adopted a resolution on the global eradication of polio, marking the launch of the Global Polio Eradication Initiative; In 1999, wild poliovirus type II was eliminated; In 2000 and 2002, the Western Pacific and Europe were certified polio-free; In 2012, Nigeria reported the last case of wild poliovirus infection type III; In 2014, India was certified polio-free. Currently, only Afghanistan and Pakistan still have WPV1 circulating.
7 Is it "making a comeback" again?
The most effective measure to prevent polio is polio vaccination. Currently, the most commonly used vaccination method is oral polio vaccine. The vaccine contains a weakened active poliovirus, which, when taken, replicates in the intestines, making the body immune. However, this weakly active virus can spread in the environment when it is released from the body, especially in areas with poor sanitation or overcrowding.
When immunity to poliovirus in an area is reduced to a certain level, attenuated viruses in oral vaccines can spread for a longer period of time. As the number of replications increases, the strain may revert to a form of the virus that causes paralyzing polio, known as vaccine-derived poliovirus (VDPV).
The polio case reported in New York State is caused by VDPV, and the patient has not been previously vaccinated and has no antibodies against the poliovirus. Following the emergence of this case, New York State intensified its polio vaccination coverage campaign and worked with surrounding states to test wastewater samples for poliovirus.
The U.S. Centers for Disease Control and Prevention said all cases were linked to people who were unvaccinated or had weakened immune systems. Most U.S. adults were vaccinated in childhood and are adequately protected.
Looking back at the century-long struggle against poliovirus, we can see humanity's confidence in continuing to write the "history of extinction" of infectious diseases. Polio is one of the few diseases that can be eradicated, with global polio cases decreasing from 350,000 cases of paralysis in 1988 to 33 reported in 2018 since the first vaccine became available. For vaccinated people, there is little risk to the virus.
But as long as one child is infected with poliovirus, children in all countries remain at risk of contracting the disease. Vaccination remains the most effective polio control measure at present, and may we see the day when polio is eradicated, "the world's children will not know the disability caused by this terrible disease."
(Some images in this article are provided by the author.) ）
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