Home History A lethal vaccine A lethal vaccineOf all countries, the United States currently has the strictest controls on new vaccines. It is not without reason. In 1955, a mistake in a laboratory meant that a new… History 17/06/2023 by Space Navy 0 Comment Of all countries, the United States currently has the strictest controls on new vaccines. It is not without reason. In 1955, a mistake in a laboratory meant that a new vaccine turned out to be extremely dangerous and in some cases fatal. As an experienced virologist, Bernice E. Eddy is not necessarily surprised when laboratory experiments lead to different results than she expected. Nevertheless, on August 30, 1954, she is shocked when she examines a specimen under a microscope. Bernice E. Eddy works on behalf of the American health authorities, and now it is her job to investigate the quality of a newly developed vaccine against polio, which has most often been called polio in Icelandic. Production of the vaccine has begun at Cutter Laboratories in Berkeley, California, and just a few days ago, Eddy injected the vaccine into a monkey but did not get the results she had hoped for. Many of the monkeys became paralyzed shortly after vaccination. To get to the bottom of this, she is now studying spinal cord samples from vaccinated monkeys under an electron microscope. Eddy runs cold water between skin and skin as she sees clusters of spherical particles appear on the glass plate under the lens. At first glance, the balls resemble tightly wound balls of yarn, but Eddy knows all too well what they are: living polioviruses. “It’s going to end in horror – I just know it.” Virologist Bernice Eddy when she discovers live viruses in vaccines. She immediately reports her findings to William Workman, head of the Office of Biological Control, which is part of the US Department of Health and Human Services and is supposed to monitor vaccine production. But Workman has a lot to do because the press and the public are clamoring for permission to be issued – every hour wasted costs new victims. That’s why the poor messages from Bernice E. Eddy never make it all the way to the expert committee that issues licenses for the vaccines of the various laboratories. After several hours of discussion, the committee decides to allow vaccines from all the laboratories. Bernice E. Eddy never receives any response to her report. It is clear to her that this could be a unique case, but she has a nagging suspicion. “It will end in horror – I just know it,” she said in a conversation with an acquaintance. A few weeks later, the biggest vaccine scandal in US history has become a reality. Historians estimate that around 120,000 children were injected with live viruses from the Cutter laboratories. Ten people died and many thousands were badly paralyzed after what later became known as the Cutter Incident or “The Cutter Incident”. However, this catastrophe also had positive consequences. That prompted the United States to introduce the world’s strictest controls on new vaccines before they are approved. Jonas Salk developed the first polio vaccine. It saved thousands of children, especially in the US. Widespread fear of paralysis The story of the polio vaccine initially seemed destined to be a continuous story of happiness. Ever since the beginning of the 20th century, polio had been ravaging the United States and Europe, and the victims were numerous. The disease mainly affected young children. They developed fever and sore throat and vomited or had diarrhea. Many children were paralyzed in their hands or feet, and some died when the paralysis reached the respiratory system. A bad epidemic in New York in 1916 killed 2,400 and crippled 9,000 for life. Most of the victims were under the age of ten. That is why polio and polio were among the names given to polio in the public’s mouth. Once here, scientists knew both the disease itself and its causes. At the beginning of the century, it became clear that this was a viral disease that was transmitted through the mouth, through faeces and through so-called droplet transmission, such as when the patient coughs or sneezes. But when it came to cure or prevention, scientists were at a loss. Parents forbade their children to go swimming or grocery shopping. There were also desperate measures: frog blood and earthworm oil were among the things believed to protect against polio. But no advice was enough. In the following decades, polio ravaged in severe epidemics. In 1952, 57,000 people were infected, and that was the largest number ever reached by a polio epidemic. Polio was so common that almost every American either knew someone or knew of someone who had been badly affected by polio. The fear of the disease was so great that in a 1952 poll, people found polio to be the second worst threat, second only to nuclear war. A concerted fundraising effort raised enough money to fund the research and development of a polio vaccine. The authorities did not fund any vaccines In the 1960s, the health and well-being of the American public was largely in the hands of private corporations and charities. The same was true for the development of the polio vaccine. The research was funded by funds from a fund called the “Research Foundation for Polio” and received donations from private individuals and charities. When Jonas Salk announced that his vaccine worked in 1955, most people thought that the authorities had already stockpiled the vaccine. However, the government was of the opinion that production and distribution were the role of companies in the market. The Polio Research Institute had nine million dollars allocated to the production. It was not enough to create herd immunity, but it was enough to protect the youngest and most vulnerable children. Fortunately, these years saw great progress in the development of vaccines against the disease. In fact, it was in large part thanks to one of the victims of polio, US President Franklin D. Roosevelt who had contracted polio at the age of 39. At the beginning of 1938, he founded the ” Foundation for Infantile Paralysis “. Although it was the president himself who founded the fund, there were no financial contributions from the state, but the institution had to rely on donations from private sources. The connection with the president had a lot to say, however, and caused a host of movie stars and other famous people to support this charity. Popular singer and actor Eddie Cantor suggested a fundraiser called the “March of Dimes” (“dime” being a nickname for a 10-cent coin) and took the idea for the title of a weekly news package in movie theaters called “The March of Times.” The fundraiser was held in January 1938 in celebration of the president’s 56th birthday and raised $85,000 for the new foundation. Salk found the solution The money raised in the March of Dimes, along with much more money, was used to support the country’s leading scientists for research. One of them was Jonas Salk. He was born in 1914, the son of Russian immigrants, and is both ambitious and meticulous, which are particularly suitable qualities for research in virology. Salk had to start from scratch, because although many scientists had tried, no one had succeeded in creating so much as a reasonably usable vaccine. But Salk’s hard work and precision paid off. For months, he cultivated the poliovirus that he kept alive in monkey kidneys. After filtering the viruses from the organic medium, the monkey kidneys, he treated the viruses with formalin, a chemical used in preservation. Salk hypothesized that this treatment would inactivate the viruses so that they would be unable to reproduce but would still be able to induce the immune system to produce antibodies. “The children lined up to get the vaccine. I had complete trust in him.” Donna Salk, when Jonas Salk vaccinated their children with his vaccine. Salk first tested the substance by vaccinating children at the DT Watsons Children’s Home just outside of Pittsburgh, and later mentally retarded boys and men at the Polk State School near Philadelphia. The attitude that there was something considered unethical about experimenting on children in institutions had not yet emerged. In the sixties of the last century, this point was almost undisputed. None of these children had any side effects and none of them developed polio. “These were the most exciting moments of my life. Everything that followed was insignificant in the context,” Salk later wrote about those days in 1952 when he was examining blood samples from vaccinated children under a microscope. To his great joy, he saw that the children produced antibodies, just as he had expected. “I did it!” he said excitedly to his wife, Donna. In 1953, he vaccinated both Donna and their three children, nine-year-old Peter, six-year-old Darrell and three-year-old Jonathan. “The kids lined up to get the vaccine,” Donna said later. “I had complete confidence in him.” Even in churches there was celebration Donna was not alone in putting all her trust in Jonas Salk. Journalists had found out about Salk’s experiments, even though they were supposed to be secret, and expressed their admiration. “Good news from the polio front,” Time magazine said next to a photo of Salk. Confidence grew even more the following year when Salk conducted a huge experiment in which 420,000 children received a vaccine, while 200,000 children in a control group received a placebo. In addition, 1.2 million children who received neither vaccine nor placebo were followed. In the 1960s, there was an epidemic of polio and many people had to be put in so-called “iron lungs” to help them breathe. The results of the experiment were that unvaccinated children were three times more likely to get polio than those who had been vaccinated. The results were presented on April 12, 1955 in front of a packed auditorium at the University of Michigan. Of the 500 in the audience, 150 were journalists or photographers. In American cinemas, 54,000 doctors watched the presentation on a special television channel. Before the presentation began, a large handcart with printed copies of the scientific article was placed in the hall for journalists. “It works!” It works!” shouted journalists to one another after flipping through the main findings in this thick pile of documents. “It was an impasse. One of the doctors had tears in his eyes,” said one of the journalists later. “This is a wonderful day for the whole world. Here we are writing the history of mankind.” US Secretary of Health when it is clear that Salk’s vaccine works. Church bells rang all over the country. In factories, workers stood still for a minute, and in churches, synagogues and mosques, congregations united in a prayer of thanksgiving. Over one shop window, the owner hung a banner with the inscription “Thank you, Dr. Salk”. “One feels as if the war is over,” someone was quoted as saying. In the afternoon of that same day, a meeting was held with representatives of the health authorities who approved the vaccine after a quick review of the report. “This is a big day. This is a wonderful day for the whole world. Here we are writing the history of humanity,” said the Minister of Health Oveta Culp Hobby after signing the approval of the new vaccine. Production began immediately. 38,000 children, mostly first and second grade school children in many states of the United States were selected for the first vaccination group. Distribution went as planned. The very same evening, cardboard boxes with the inscription: “MULIPOPIA VACCINE” were delivered to doctors’ offices around the country. ESSENTIAL!” A seven-year-old girl died However, on April 24, 1955, just a few weeks after the first children were vaccinated, an ominous report came from a doctor in Idaho. One of his patients, a seven-year-old girl named Susan Pierce, had developed a fever and paralysis in her left arm, the arm into which the vaccine was injected. The next day, the phone rang with William Workman, the same representative of the health authorities to whom Bernice Eddy had sent her report on live viruses nine months earlier. Now, a one-year-old child had paralyzed his legs eight days after vaccination, the director of the Chicago Health Authority announced. A large number of children had been vaccinated before the authorities realized that something was wrong with the vaccine from the Cutter laboratories. This call was just the beginning. The next day, Workman had to answer the phone again. Now it was the California Department of Health that called. Two seven-year-old boys in San Diego had paralysis of the left arm seven days after vaccination. Later that day three more cases were reported, and the next day the first paralyzed patient, little Susan Pierce, was reported dead. Salk’s vaccine was produced in many places, but the vaccine that caused the disease all came from Cutter, a relatively unknown laboratory in Berkeley, California. Workman was confused. These children had received only one dose of the vaccine and not two as was the minimum required. It was also possible that these children had been infected before they were vaccinated, but it raised suspicions that in any case the children had become ill about a week after the vaccination. In addition, the paralysis seemed to start at the site of the vaccine injection. Doctors were also able to see that there was no polio epidemic where these children lived. An electron microscope shows round, active polio particles of the kind with which thousands of children were mistakenly vaccinated. Filled with despair US Surgeon General Leonard Scheele took no chances. On April 27, two days after receiving news of the first case, he recalled all vaccine from the Cutter lab. He also issued an announcement to calm the public. “First of all, I would like to assure the parents of children who have been vaccinated against polio this spring, that according to the best belief of the health authorities, there is nothing to fear,” said Scheele. He was wrong. Reports of vaccine-related illness were now pouring in. In the first 24 hours after the recall, a total of 11 vaccinees showed clear signs of polio. And 24 hours later, 25 children were either paralyzed or dead. Despair now spread, not least among doctors. School children received the vaccine for free, but the pharmaceutical companies also sold vaccines directly to doctors, many of whom had started vaccinating their own families. “I was on the phone non-stop for a whole 24 hours. Doctors at that time only vaccinated babies, but 90% of the people who called me were doctors who had vaccinated their own children, their mothers, aunts and neighbors and were now worried about what might happen,” said Tom Coleman, one of Salk’s assistants. Many employees of the pharmaceutical companies had also received the vaccine: “We were filled with despair. After all, our own children had also received this vaccine,” said Frank Deromedi of the Cutter Laboratory. Salk had miscalculated During all of this, health officials worked frantically to figure out what had gone wrong. All cases of disease and death were carefully investigated. Suspicion soon focused on two Cutter batches – numbers 19468 and 19764. The vaccine from these two batches had killed five children and paralyzed 51. In late April, two Williams Workman employees, Karl Habel and William Tripp, began a detailed investigation of the Cutter laboratory and made a shocking discovery. The study found that five of the last seven production batches contained live viruses, a clear sign that something was seriously wrong in the lab. However, Habel and Tripp could not answer the question of how this had happened so far. Fatal decisions Converting the deadly polio virus into a safe vaccine was what Jonas Salk thought he knew all about. His self-confidence combined with poor supervision by the authorities was to cost both life and health. Most scientists believed that live but weakened viruses were needed for vaccines. Jonas Salk disagreed and instead decided to “deactivate” the virus. This made the virus incapable of multiplying, but it was still enough to activate the immune system and make it produce antibodies. For this procedure, Salk used formalin. However, he only tested the method on relatively small doses of the virus and then realized that it worked just as well on larger doses. However, handling a large viral population required much longer than Jonas Salk had anticipated. This oversight meant that live viruses could be hidden in the vaccine. Seven things that caused the horror A very dangerous virus was used There are three types of poliovirus, all of which are divided into substrains. Salk used all the models, including the Mahoney strain which is very difficult to deactivate. Poor filters An important step in production was to filter out all traces of monkey kidney, otherwise the viruses could retain their activity. The Cutter lab used fast glass filters that did not capture all cells. Experiments on monkeys were not enough In the Cutter laboratory, the product was tested by injection into the muscles and brains of monkeys without visible traces. Had the injection been made directly into the spinal cord instead, the probability of correct results would have increased. The Cutter lab lacked experience In contrast to other manufacturers, the Cutter laboratory had produced very little human medicine. For that reason, people were not sufficiently vigilant in the production process. The virus was in the refrigerator for too long The Cutter lab refrigerated the filtered virus for weeks before inactivating it with formalin. It was not according to safety standards and the laboratory was therefore the only one doing this. Lack of calculations Salk never calculated exactly how long it would take to treat viral doses for all viruses to be reliably inactivated. At the Cutter laboratory, this calculation was never attempted either, and this mistake was the main factor. The health authorities were sleeping on their guard Virologist Bernice Eddy discovered live viruses in a sample at the Cutter lab in November 1954. She immediately notified the relevant authorities, but no one responded. Observations and conversations with staff showed that the company complied with applicable regulations and performed the required tests. It wasn’t until Habel and Tripp called a meeting with representatives of all the vaccine manufacturers that something happened to them. Habel and Tripp expected that at the meeting it would become clear that somehow things were done differently at Cutter than the other manufacturers, and were therefore quite surprised when this turned out not to be the case at all. Namely, the representatives of the other companies pointed out that they had also had problems with deactivating viruses. Although Salk was certainly very thorough, it turned out that he had not calculated correctly how long the viruses would have to be treated with formalin. Salk knew that the disinfectant formalin inactivated viruses in small amounts, but his calculations for larger doses were based on a specific assumption – that the viruses were inactivated at the same rate regardless of the viral load. It simply did not turn out to be true. The polioviruses were easily deactivated when, for example, 100 vaccine doses were treated at once, but it happened much more slowly when the doses were many times larger. Salk had assumed that the treatment time could simply be doubled when the viral load was doubled. It soon became clear to Habel and Tripp that no one knew how long it would take to treat large doses of virus with formalin for no active viruses to remain. The fatal failure in the production of the polio vaccine prompted US authorities to begin extensive inspections before new vaccines are approved. The horror made American vaccines the safest in the world After the serious mistake in the Cutter laboratory in 1955, the American authorities introduced very strict requirements regarding the acceptance of vaccines. Even today, these are the strictest rules in the world. When Salk’s vaccine production began in the spring of 1955, vaccine development was almost completely independent of laws and regulations. If the minimum requirements were met, any laboratory could produce and test the vaccine according to its own rules. The tragic consequences of inoculation with a vaccine from the Cutter laboratory changed this environment. In June 1955, the control was transferred from a small sub-division in the Department of Health to the DBS (Division of Biologic Standards), which was a completely new organization and reported directly to the US Health Service. DBS was supposed to enforce the new and much stricter rules that the authorities now put in place. For example, requirements were made for a certain number of production batches that had to be completely flawless before the production was allowed to be used – a requirement that is still enforced today. Precisely because of the Cutter mistakes, vaccine production in the United States is now subject to one of the strictest regulations of any country. Now it is the FDA (Food and Drug Administration) that is in charge of the control and monitors both experiments and production as well as possible side effects of vaccines. Two years later, it became clear that the filters used in the Cutter laboratory were not as good as those of other manufacturers. As a result, cells from the monkey kidneys, where the viruses were cultured, were able to escape. If there was any remaining of these cell remnants, that remainder could protect the viruses in the formalin. It was to save time that people had chosen filters that allowed a faster flow through, but this had the disadvantage that it was not guaranteed that they would clean as surely as needed. Control failed Williams Workman’s staff discovered that Salk’s miscalculations and Cutter’s poor filters were not the only reasons for the crashes. The health authorities had also been rather hasty and had not monitored the production well enough. The warning from Bernice Eddy, for example, never got further than Williams Workman, who in his haste either forgot or did not pay attention to the information. Cutter’s production records also proved ineffective as the lab was not required to record information about discarded production. There was also no law on how long viruses could be refrigerated before treatment with formalin. All of this lack of oversight meant that relatively simple errors ended up causing catastrophes. After 1955, when Salk’s vaccine was introduced, the incidence of polio in the United States decreased rapidly. A few years later, Dr. Albert Sabin’s new vaccine was introduced. The vaccine won The tragedy that followed the mistake at the Cutter lab prompted health officials to immediately halt vaccinations. It was done on May 6, 1955, but vaccinations soon started again. A special committee had then been established which organized extensive and strict supervision to ensure full safety. Soon after this, the vaccine began to triumph, and by 1957 the number of polio cases had dropped to 5,600 from more than 57,000 in an epidemic five years earlier. Nevertheless, the Cutter accident had damaged the reputation of Salk’s vaccine so much that space was created for a new vaccine, developed by the Polish-American doctor Albert Sabin. The new vaccine was simply swallowed and it immediately became popular in other parts of the world. By 1961, it had also become more popular in the United States. Polio is now considered to have been eradicated in the western countries and the disease has become rare worldwide. A campaign by the World Health Organization (WHO) reduced the number of cases from around 350,000 in 1988 to just 175 cases in 2019. Historians now do not know how extensive this catastrophe was, but it is believed that around 120 thousand doses of live viruses were produced. The people who got sick then infected others and the incident thus caused a chain reaction, especially among families and neighbors. Of the children who were infected, 40,000 had limited muscle power, while 56 children were severely paralyzed and five of them died. Even if the laws and regulations had been followed, the Cutter laboratory had to pay large damages due to the basic warranty, but the “implied warranty” clause is an American standard clause in contracts and is intended to ensure that products meet basic quality requirements. Brian May, who was vaccinated with the Cutter vaccine at the age of four, received the highest compensation. He had to wear an “iron lung” for 16 months and was paralyzed in both arms and legs for life. He received $600,000 in compensation, the highest compensation ever paid. However, it was absolutely impossible for the Cutter laboratory to recover the lost trust. The authorities stopped vaccinations on May 6, 1955, but they soon resumed, after it had been ensured that the vaccine met all the requirements and constant quality control had been established. However, parents were hesitant for a long time and it took several months before vaccinations really spread again. Now the vaccinated could be absolutely sure. As a direct result of the incidents at the Cutter lab, strict control restrictions were placed on production – and the same has been true of all vaccines ever since. Read more about the polio vaccine Paul A. Offit: The Cutter Incident , Yale University Press, 2007.