Anne Gottsdanker has only hazy memories of the April day in 1955 when she became one of the first children in the country to receive Dr. Jonas Salk’s polio vaccine. She was 5 years old and got a shot six days after it was approved.
She also remembers bits of the life-altering experience she endured about a week later. Gottsdanker and her family were on their way home to Santa Barbara, Calif., after visiting her grandparents near the Mexican border. Her head hurt during a stop for ice cream, and she threw up in the car. Before long, she couldn’t move her legs.
Gottsdanker was one of 120,000 children inadvertently injected with the live infectious poliovirus from a vaccine manufactured by a northern California laboratory. About 70,000 people developed muscle weakness, 164 were severely paralyzed ― including Gottsdanker ― and 10 died.
Now, as President Trump vows to distribute a COVID-19 vaccine by year’s end under a program called “Operation Warp Speed,” she worries that the ambitious plan could backfire. Despite the remarkable success of vaccines in the 20th century, several immunization efforts ― even Salk’s triumph over polio ― have harmed some of the people they were supposed to protect. Health experts say haste or carelessness played a role in those missteps.
“It horrifies me,” said Gottsdanker, 70, a retired college professor in Lancaster, Calif., who uses a wheelchair, has multiple health problems, and would welcome a coronavirus vaccine, as long as it has been proven safe. “What people don’t realize is that when a person catches a disease through a vaccine, it won’t just affect them then. It will affect their entire life.”
Some scientists who have worked on vaccines, as well as historians who have studied them, share her concern. If a poorly designed or manufactured vaccine is distributed, they argue, it could erode public confidence in vaccines in general and exacerbate declining rates of childhood immunizations, already a serious problem.
But Dr. Francis Collins, director of the National Institutes of Health, which is involved in Operation Warp Speed, said the “Star Trek”-evoking name reflects technological breakthroughs that have made it possible to develop and test vaccines on humans faster than ever.
The Cambridge biotech Moderna, he noted, began testing the first potential COVID-19 vaccine in a clinical trial a mere 63 days after company scientists obtained the genetic sequence for the virus. Moderna is injecting genetic material that instructs cells to make proteins that provoke an immune response. Researchers have explored that approach for several years, but it has yet to produce an approved vaccine.
“It’s not about cutting corners when it comes to safety and efficacy,” said Collins, who discovered the genes associated with a number of diseases and led the Human Genome Project of the 1990s. “The warp speed part is to figure out how to do all the right things but cut out the delay. I want to be very reassuring about that.”
Trump unveiled the program on May 15 at a Rose Garden news conference. The aim, he said, was to make hundreds of millions of doses of a vaccine available by year’s end through a partnership between the government and drug companies. Traditionally, vaccines take years, if not decades, to develop. Trump likened the new effort to the World War II-era Manhattan Project, which produced the first nuclear weapons.
Although Trump questioned the safety of vaccines before he became president ― he repeatedly cited a discredited link between childhood vaccines and autism — the scientific evidence that their benefits far outweigh risks is overwhelming.
Dr. Paul Offit, author of “The Cutter Incident: How America’s First Polio Vaccine Led to the Growing Vaccine Crisis,” a 2005 book about Gottsdanker and other children infected with the live poliovirus, wrote that “no single medical advance had a greater impact on human health."
Vaccines have completely or largely eliminated such dreaded diseases as measles, diphtheria, rubella (German measles), whooping cough, and polio in the United States. Smallpox, a scourge estimated to have killed 500 million people worldwide, was officially declared eradicated in 1979, according to the World Health Organization.
Nonetheless, that remarkable record has occasionally been marred by blunders in which haste conspired with problems in design or manufacturing to produce a vaccine that was ineffective or dangerous.
No episode illustrates the high stakes more than the largely forgotten debacle at Cutter Laboratories in Berkeley, Calif., one of the worst pharmaceutical disasters in history.
Polio terrified Americans in the 1950s, when it ranked second only to the atomic bomb as the biggest fear in public opinion polls. Deadly summer outbreaks prompted parents to keep children away from swimming pools and movie theaters. Photographs of young polio survivors with heavy braces on withered legs or bed-ridden in iron lungs fueled the urgency to find a vaccine.
On April 12, 1955, scientists announced that the Salk vaccine made from a killed poliovirus had been tested on nearly 2 million children and was safe and effective. Six days later, Anne Gottsdanker and her 7-year-old brother, Jerry, were injected with the vaccine by their pediatrician. It had been manufactured by Cutter, one of five companies that obtained Salk’s formula.
But Cutter’s vaccine contained the live poliovirus, not a killed one to stimulate an immune response without making people sick. The company had departed from Salk’s safe production protocols as it hurried to make the vaccine, including how long the virus must be treated with formaldehyde to inactivate it.
“Mass production is actually the hardest part of making a vaccine,” Offit, author of the Cutter book, said in an interview. He directs the Vaccine Education Center at Children’s Hospital of Philadelphia and is co-inventor of a vaccine to prevent rotavirus infections, which cause diarrhea. Cutter, he said, “made it badly.”
Jerry Gottsdanker didn’t get sick, but Anne lost complete use of her right leg and most of her left leg.
A suit filed against Cutter by her family and that of another injured child went to trial in 1957 in Oakland, Calif. The legendary personal injury lawyer Melvin Belli represented the Gottsdanker family. He had Anne walk with her crutches in front of the jury.
“It was embarrassing," she recalled. Of her paralyzed legs, she said, “You don’t lose the feeling, but the motor neurons are killed off. You tell your leg to move, and it just goes, ‘Really? You want me to do what?' ”
The jury awarded the two children and their families a total of $147,300 in damages.
Cutter’s devastating mistake led to rigorous government regulations of vaccines. But the legal precedent also discouraged drug firms from making vaccines for other diseases, Offit said. That trend that has only begun to change with the COVID-19 epidemic. As of last year, only four major drug companies were manufacturing vaccines.
In 1976, there was a different kind of vaccine debacle.
That February, an Army recruit at Fort Dix in New Jersey died from the flu, and other recruits fell ill. Two weeks later, health officials blamed a new form of swine flu that appeared to be eerily similar to the strain that caused the 1918 Spanish flu. That pandemic is blamed for at least 50 million deaths worldwide, according to the Centers for Disease Control and Prevention.
President Gerald Ford hastily convened a group of scientists to assess the situation and in March announced a government-funded plan to vaccinate “every man, woman, and child in the United States." More than 40 million people soon got vaccinated, including Ford, who was photographed smiling as the White House doctor jabbed him.
But it turned out that the 1976 flu wasn’t related to the 1918 virus. People who were infected suffered only a mild illness. The vaccine, however, caused side effects in some children, including high fevers and sore arms. And several hundred people who were inoculated developed Guillain-Barre syndrome, a rare disorder in which the body’s immune system attacks nerves, although it remains uncertain whether the vaccine was responsible.
Some critics accused Ford of manufacturing a public health emergency to boost his reelection prospects, but David Oshinsky, a Pulitzer Prize-winning historian, said he believes Ford sincerely wanted to avert an epidemic. Nonetheless, Oshinsky said, the rush to deploy an ill-conceived vaccine undermined the faith that many Americans had in science, sowing the seeds of today’s anti-vaccine movement.
“There are public opinion polls that say 50 percent of people will take a COVID-19 vaccine when it comes out,” said Oshinsky, director of the Division of Medical Humanities at the NYU School of Medicine, who recently cowrote an article in the Journal of the American Medical Association about the dangers of rushing a vaccine. “That means that 50 percent won’t take it, and that has a direct correlation with the anti-vaccine movement gaining traction as a result of what happened in 1976.”
A recent episode on the other side of the world illustrates how a vaccine can backfire if isn’t rolled out cautiously.
In 2016, the government of the Philippines began a massive campaign to inoculate nearly 1 million schoolchildren with the first vaccine for dengue fever. A painful mosquito-borne tropical disease, dengue afflicts hundreds of millions of people around the world.
Sanofi, the French pharmaceutical giant, had worked on the vaccine for 20 years and tested it on more than 35,000 children. The company shared its results in a 2015 article in the New England Journal of Medicine. Dr. Scott Halstead, a Bethesda, Md., physician who is considered one of the world’s foremost authorities on viruses spread by mosquitoes, remembers reading the results with growing alarm.
In children who had never been exposed to the dengue virus, the vaccine created antibodies that actually appeared to worsen the disease if the youngsters were later infected, he said. Indeed, young children who received the vaccine and later caught dengue were more likely to be hospitalized with severe illness than those who hadn’t been vaccinated.
Halstead wrote several articles in scientific journals and even made a video to warn the Philippine government not to distribute the vaccine, called Dengvaxia. Nonetheless, government officials moved forward with the immunization campaign. About a year and a half later, Sanofi announced that it had found evidence that the vaccine did in fact increase the risk of hospitalization in children with no prior exposure, and the program was halted.
The government revoked the license for the vaccine. It also filed criminal charges against Sanofi officials and former and current Philippine health officials over 10 deaths that it said were linked to use of the vaccine. A public backlash against vaccines contributed to major outbreaks of measles in the Philippines.
Halstead fears something similar could happen if a COVID-19 vaccine is rushed.
“There’s enormous pressure to come up with a vaccine,” said Halstead, 90, who has written an unpublished paper on challenges facing the creation of a COVID-19 vaccine. “This, unfortunately, is a complicated virus, and it’s going to require more care. That’s why it’s so important to remember history."
Collins, the head of the NIH, said scientists involved in Operation Warp Speed are aware of historical problems with several vaccines. But he said vaccine development has changed so much in recent years that some concerns are unwarranted. For example, he said, there couldn’t be another Cutter incident with a COVID-19 vaccine because none of the formulas under serious consideration by federal officials uses a killed virus.
Instead, scientists in the government and at drug companies and academic laboratories are collaborating on a mix of cutting-edge approaches. They include vaccines that rely on genetic material, called messenger RNA, to teach a person’s immune system to defend against the coronavirus, and vaccines that use a harmless virus as a Trojan horse to deliver the genetic sequence for the coronavirus into human cells to produce an immune response.
There are more than 120 coronavirus vaccines in development worldwide, and Collins said that “if everything goes right,” he thinks one could start being rolled out by year’s end. That would require drug companies to manufacture huge quantities of vaccines before the completion of clinical trials and to discard them if the vaccines don’t pass muster, he said.
To make that financially tenable, the government is bankrolling some private efforts. In the case of Moderna, the federal Biomedical Advanced Research and Development Authority pledged up to $483 million in April to help the biotech manufacture a messenger RNA vaccine, before the first phase of the clinical trial was even completed. The government made the commitment even though no mRNA vaccine has ever been approved.
“But that doesn’t mean you’re going to go forward if you see a safety problem or an efficacy problem,” Collins said.
With COVID-19 blamed for the deaths of more than 100,000 Americans and a lockdown that is only starting to ease, “I don’t think anyone wants us to be on Operation Slow Boat," Collins said. “We are anxious to get it done, but not to compromise on safety.”
Jonathan Saltzman can be reached at firstname.lastname@example.org