In 1775, Gen. George Washington was fighting two enemies. His visible enemy was the British, with whom the Colonists had begun fighting at the battles of Lexington and Concord. Washington’s second enemy was invisible, but deadlier than British muskets: smallpox.
A smallpox epidemic threatened Washington’s Continental Army. Fortunately, Washington had experience with the disease (he had caught and survived smallpox while in the Caribbean Islands) and sought to have his troops inoculated.
Inoculation was new and controversial in Colonial America, even outlawed in places. It didn’t help that the method of inoculation practiced at the time was risky. “Called variolation, the procedure entailed making a small incision in a patient’s arm and inserting a dose of the live virus large enough to trigger immunity but small enough to prevent severe illness or death,” writes Andrew Lawler in an April 2020 National Geographic article.
But Washington was a firm believer in the science-based treatment. While soldiers already in the army were given a choice (and many refused), Washington insisted that all new recruits be inoculated. By the end of 1777, some 40,000 soldiers had been vaccinated.
“A compelling case can be made that his (Washington’s) swift response to the smallpox epidemic and to a policy of inoculation was the most important strategic decision of his military career,” Lawler quotes historian Joseph Ellis as saying.
This story touches on the dilemma of immunization as a medical treatment. On the one hand, vaccines have saved millions of lives. Yet despite being applauded as a medical miracle, vaccines have always generated a level of public distrust.
A powerful choice
“This is not a new problem. It has waxed and waned ever since we’ve had vaccines,” said Dr. Christopher Martin, a professor in the West Virginia University Schools of Public Health and Medicine. Martin also serves on the West Virginia COVID-19 Vaccine Medical Advisory Group.
“When it comes to vaccine hesitancy, people fall along the spectrum. At one end are people like me, who love vaccines. Whenever a new vaccine comes up that’s indicated for me, I get it right away,” Martin said.
“There’s another group at the other end of the spectrum that are completely resistant to any kind of data or argument. There’s nothing you can say. As my Irish father used to put it, you might as well ‘save your breath to cool your porridge.’”
But most people fall somewhere in the middle. These are the ones Martin tries to reach. “Calling someone anti-science isn’t helpful,” he said. “We have to tailor the message. In focus groups it came out that West Virginians’ concern is ‘I don’t want to be told to have this vaccine.’ They are concerned about personal liberties.
“That’s why our theme for the COVID vaccine is that it’s a choice. We try to get people to understand what a powerful decision they can make to protect themselves.”
An evolving history
A brief look at how vaccines developed in this country can shed light on the present cultural divide.
While variolation can be traced back to ancient China, it is Edward Jenner who is generally credited with devising the first vaccine. In 1796, he inoculated a 13-year-old boy with the vaccinia virus (cowpox) and demonstrated that it gave immunity to smallpox. The practice quickly became widespread.
Louis Pasteur began experimenting with attenuated vaccines in the late 1800s. Attenuation takes an infectious pathogen (a bacteria or virus) and makes it less virulent. Although weakened, the pathogen is still viable.
Pasteur developed a rabies vaccine in 1885. His research led to other attenuated vaccines, including ones for cholera, anthrax, measles, mumps, rubella and yellow fever.
Attenuated vaccines are in contrast to inactivated vaccines where a “killed,” nonviable version of the germ is used. Generally, inactivated vaccines do not provide long-term immunity; additional shots could be necessary (the annual flu shot is an example).
Over the next 200 years, mass implementation of the smallpox vaccine led to the disease being eradicated globally in 1979 — one of the greatest successes of modern medicine.
Campaign against polio
Research for a polio vaccine began in the 1930s. Jonas Salk was the first virologist to become a celebrity after he developed an inactivated polio vaccine in 1954.
Polio is a disabling disease caused by the poliovirus. It can infect a person’s spinal cord, causing paralysis and sometimes death.
Children are especially vulnerable, and 1950s American families were terrified of the disease. It was said fear of polio was second only to fear of the atom bomb. An epidemic in 1952 resulted in more than 21,000 paralytic cases and more than 3,000 deaths, according to the Centers for Disease Control.
In 1955, a nationwide polio inoculation campaign began for schoolchildren, sponsored by the March of Dimes. But the campaign was quickly suspended when it was discovered that Cutter Laboratories in California had produced defective batches of the vaccine.
Cutter was one of five companies producing the polio vaccine. A flaw in the lab’s manufacturing process led to batches of vaccine being distributed where the virus was not inactivated. As a result, more than 200,000 children received a polio vaccine that contained live, viable virus. It was later determined that the faulty batches caused an estimated 40,000 cases of polio, with about 200 cases leading to paralysis. Ten children died.
As tragic as these numbers were, they were a small fraction of the casualties caused by natural polio each year during this period.
The incident led to tighter federal regulations overseeing the production of vaccines. Pharmaceutical companies made improvements to their production processes and applied more rigorous safety testing. The inoculation campaign was resumed and polio cases began to drop.
The Salk vaccine was later replaced by an oral attenuated vaccine. Many of the Baby Boom generation remember lining up as schoolchildren in the 1960s to swallow a sugar cube dosed with the polio vaccine.
By 1979, there were no new cases of polio originating in the United States. The World Health Organization and other groups are still working to eradicate polio globally.
Litigation and shortages
Not surprisingly, Cutter Laboratories was taken to court over its botched rollout of the vaccine. In the landmark case they were declared not at fault, but still liable for their product. This “liability without negligence” decision would have major repercussions for the pharmaceutical industry.
Dr. Paul A. Offit addressed the mixed legacy of this legal precedent in his 2005 book, “The Cutter Incident: How America’s First Polio Vaccine Led to the Growing Vaccine Crisis.” He contends that the verdict in the court case against Cutter made vaccine manufacturers an easy target for litigation and huge monetary awards from juries.
Such litigation persisted despite overwhelming consensus from the scientific and health communities that vaccines were low risk and that adverse effects were rare. Pharmaceutical companies began to shy away from vaccine research and manufacturing because of liability issues.
Pharmaceutical and biotech companies continued to be hauled into court throughout the 1970s and 1980s, and supplies were threatened. By 1985, for example, only one company was still making the pertussis vaccine (for whooping cough) — a critical vaccine for childhood safety.
“Vaccines were the first medical product almost completely eliminated by litigation,” Offit said, discussing his book in an American Enterprise Institute video in 2006.
Congress saw that action was needed to protect vaccine manufacturers and health care providers and passed the National Childhood Vaccine Injury Act in 1986, which included the National Vaccine Injury Compensation Program.
This law created a special “vaccine court” to handle disputes and shield vaccine manufacturers from most lawsuits. The law was upheld in a Supreme Court ruling in 2011.
Despite this protection, vaccine shortages became an intermittent problem. Offit gives more examples. In 1998, the tetanus vaccine was in such short supply that its use was restricted to emergency rooms. The flu season of 2003-2004 began early and created a demand that exceeded supply. The following year proved even worse — with 30 million fewer doses of flu vaccine than the year before.
There have been shortages of nine of the 12 vaccines routinely given to children — including the vaccine for meningitis (pneumococcus).
“Parents could only hope that their children weren’t among the thousands permanently harmed or killed by pneumococcus every year,” Offit writes.
Distrust derails Lyme disease vaccine
Lyme disease is a bacterial infection transmitted to humans through the bites of certain types of ticks. Symptoms include fever, fatigue, joint pain and rash. Left untreated, the disease can lead to serious joint and neurological complications. The CDC says cases are on the rise. EPA studies show that climate change is likely a factor in increasing the range of ticks that carry infection.
Only one company has ever marketed a Lyme disease vaccine. SmithKline Beecham (now GlaxoSmithKline) licensed the LYMErix vaccine in 1998, and would end up distributing some 1.5 million doses.
Anecdotal reports surfaced of people who said they developed arthritis after getting the vaccine. Lyme disease itself can cause chronic arthritis, but controlled case studies did not show a higher incidence of arthritis as an adverse effect of the vaccine.
An advisory panel by the Food and Drug Administration confirmed this conclusion, as did a report from the National Institute of Allergy and Infectious Diseases, which concluded that “the rate [of arthritis] was not shown to be elevated among vaccine recipients.”
According to CDC statistics, some 23% of adults in the U.S. get some form of arthritis (in West Virginia, the figure is 33.6%). In all likelihood, the people who developed arthritis would have done so regardless of whether they received the vaccine or not.
Even though no credible evidence surfaced to link the vaccine to these claims, that didn’t stop anti-Lyme vaccine groups from forming or media outlets from carrying their anti-vax message to the general public. A class action lawsuit was filed on behalf of 121 people.
“It was a fiasco that has really never occurred to any other vaccine,” said Dr. Stanley Plotkin, an emeritus professor of pediatrics at the University of Pennsylvania and veteran vaccine researcher, in a 2019 Scientific American article.
With demand dampened by the distrust and backlash, the company pulled the LYMErix vaccine from the market in 2002. Today, 20 years later, there still is no available human vaccine for Lyme disease.
COVID-19 vaccines: Urgency and suspicion
While Lyme disease is not deadly, the same can’t be said of COVID-19. But a significant segment of the population is showing hesitancy over receiving either of the two COVID-19 vaccines currently being distributed.
Advances in immunology, microbiology and molecular genetics have led to new categories of vaccines in recent years. Both the Pfizer/BioNTech and Moderna COVID-19 vaccines approved by the FDA for emergency use are made from messenger RNA (mRNA).
These vaccines are different from traditional vaccines discussed above, in that they do not contain either weakened attenuated virus or inactivated virus proteins.
Instead, mRNA uses synthetic genetic material that encodes a harmless piece of viral protein — in this case, the spike protein in the SARS-CoV-2 coronavirus.
The synthetic mRNA issues this code to the body’s cells and “teaches” them to build the protein, which triggers the body’s immune response, the same as with a natural infection. This builds up our immunity to the virus. How long this immunity will last is still unknown.
The Pfizer and Moderna vaccines are the first mRNA vaccines to advance through all the clinical trial stages and be approved for use.
“These vaccines use a new platform [mRNA], but there’s no additional risk,” Martin said. “Long before COVID came out, we had done the science. All the pioneering work has been done.”
In fact, research into mRNA vaccines has been ongoing for decades. “If there was a real problem with the technology, we’d have seen it before now for sure,” said Michael Goldman, a professor of immunology and director of the Innovative Medicines Initiative, in “Horizon,” a European Union research and innovation publication.
Some people have expressed concerns, not with the mRNA platform as such, but with the compressed time frame in which COVID-19 vaccines were rushed into production.
But one of the advantages of the mRNA platform is speed. It takes far less time to produce a synthetic mRNA vaccine than with traditional vaccines.
Also, as Martin points out, in this case the companies began manufacturing the vaccines before clinical trials were completed. “They did steps in parallel, which was a financial risk, not a safety risk,” Martin said.
“There is nothing different about the clinical studies that were done. I’ve had both doses. The only negative experience for me is knowing it’s not yet available for more people.”
Martin adds that psychological considerations come into play surrounding vaccine hesitancy. “Nothing is risk free,” he said. “But we aren’t very good at perceiving risk accurately. Subjectively, doing nothing feels safer. People feel that doing something — making a choice to get the vaccine — is more risky. But it is clear that if you don’t get vaccinated, you are at greater risk.”
After releasing its instructions to the cells, the mRNA is quickly broken down by enzymes and does not enter the nucleus of a cell. “It’s not DNA. It has nothing to do with your genetic material,” Martin said. “And it’s not possible to get COVID from the vaccine.
“Allergic reactions are possible, but very, very rare. If it happens, a reaction is entirely manageable. Vaccination clinics are easily equipped to handle that.”
Some people have reported mild symptoms, particularly after the second shot. In a statement, the FDA said that “the most commonly reported side effects, which typically lasted several days, were pain at the injection site, tiredness, headache, muscle pain, chills, joint pain, and fever ... more people experienced these side effects after the second dose than after the first dose.”
But Martin takes issue with calling these side effects. “You might feel unwell or have a low-grade fever,” he said. “That’s not a side effect — that’s the primary effect. That’s just your immune system at work. It means you are going to be one of the 95% who are protected.”
Scientists question whether COVID-19 will ever be eradicated, as with smallpox, or even largely eliminated, as with polio. What is certain is that, whatever happens, vaccines — and the public’s willingness to trust them — will play a major role.
Ultimately, overcoming a pandemic isn’t just about science. It’s about culture and the perceptions that people bring to science.