A century ago, one of the biggest safety concerns about vaccines involved bacterial contamination. In 1916, four young children died in South Carolina after receiving typhoid vaccine that had been contaminated with Staphylococcus aureus bacteria. Twelve years later, 12 children in Queensland, Australia, died from tainted immunizations against diphtheria.
In the 1930s, vaccine makers began using a preservative called thimerosal to stave off microbial growth in their products. For the next six decades, it didn’t receive much notice; ill effects appeared limited to minor local injection-site reactions, according to the US Food and Drug Administration.
That changed in 1999, when US health officials asked pharmaceutical companies to remove thimerosal from vaccines. There was no evidence that it caused harm in the quantities used, but thimerosal contains a form of mercury, and questions had emerged about whether it could cause neurotoxicity when given in childhood vaccinations.
Vaccine makers have removed it from all but a few shots, such as multidose vials of flu vaccine. In the meantime, subsequent studies have confirmed no link between thimerosal in vaccines and neurodevelopmental issues, including autism, and autism rates have continued to rise.
So public health experts were puzzled when the preservative appeared on the agenda for this week’s meeting of outside vaccine advisers to the US Centers for Disease Control and Prevention.
“I actually don’t know any pediatric practices that even use that multidose influenza vaccine,” said Dr. Sean O’Leary, a pediatrician at Children’s Hospital Colorado and former liaison to the CDC’s Advisory Committee on Immunization Practices, or ACIP, for the American Academy of Pediatrics.
The group is meeting on Wednesday and Thursday for the first time since US Health and Human Services Secretary Robert F. Kennedy Jr. dismissed the committee’s previous 17 members, claiming they had conflicts of interest, and days later installed eight new advisers. Public health experts and lawmakers have called into question the credentials and backgrounds of some of the new panelists, and just before the meeting began, one member withdrew during the financial holdings review, an HHS spokesman said, bringing the panel down to seven.
A presentation “regarding thimerosal in vaccines” is scheduled for Thursday morning, followed by “proposed recommendations” specifically about thimerosal in flu vaccines, according to an agenda posted Monday. The meeting is scheduled to conclude with a vote on the latter, a move that could lead to official CDC policy if adopted by agency leadership – or, without a confirmed director in place, by Kennedy.
The last-minute addition of thimerosal to the agenda was a red flag for vaccine experts, who consider the science settled and fear that Kennedy – who led an anti-vaccine group called Children’s Health Defense – is seeking to sow doubt about vaccine safety. Another former Children’s Health Defense leader, Lyn Redwood, is slated to make a presentation on the topic at the meeting.
Here’s how thimerosal became such a hot-button issue.
A focus on mercury
In 1997, Rep. Frank Pallone, a New Jersey Democrat concerned about mercury pollution in his community’s lakes and rivers, attached an amendment to a US Food and Drug Administration reauthorization bill that would require the agency to catalogue intentionally introduced mercury compounds in drugs and food.
That led to a possibly startling discovery: “As people looked in vaccines, there was the potential that, by six months of age, infants could have received more thimerosal than was listed in several sources of what was considered safe levels of mercury,” said Dr. Walter Orenstein, who was director of the National Immunization Program at the CDC at the time.
But those limits were set for methylmercury, the kind found in some fish, which is known to be toxic. Thimerosal contains ethylmercury, a different compound that’s “intrinsically less stable, and more readily metabolized, than methylmercury,” said Dr. Matthew Rand, an associate professor in the Department of Environmental Medicine at the University of Rochester who studies mercury toxicity.
That means it’s cleared from the body more quickly than methylmercury, according to the CDC, “and is therefore less likely to cause any harm.” The FDA notes that there were no existing guidelines for ethylmercury.
Still, the finding led to a number of emergency meetings among federal health officials and outside groups to determine what should be done, Orenstein recalled.
“While there was no evidence of harm from thimerosal, the general feeling was, ‘let’s get rid of it, because we don’t need it,’ ” he said. Moving to single-dose containers alleviated the need for a preservative, although it came at a higher expense for manufacturers.
In 1999, the FDA sent a letter to manufacturers of US vaccines requesting their plans to remove thimerosal, and by 2001, the compound had been removed from or reduced in all vaccines routinely recommended for children under 6 in the US, according to the CDC.
The message from public health agencies, Orenstein said, was “we’re going to make safe vaccines even safer.”
Parents seeking answers
But the die was cast. Vaccines had already been tied to autism in 1998 by British doctor Andrew Wakefield, who published a since-retracted paper that claimed the measles-mumps-rubella vaccine was linked to autism, although not because of thimerosal – the MMR vaccine never contained the preservative.
Still, parents of children with autism were seeking answers.
One of those parents was Redwood, who said that in 1999, she tallied up her son’s mercury exposure and found “at two months of age, he had received 125 times his allowable exposure to mercury based on EPA’s guidelines in his weight.”
“That was a real answer for me,” Redwood said in a video posted by Children’s Health Defense this month, “because my son at this time was almost 5 years old, and he had regressed developmentally after his first year of life and was diagnosed with autism.”
Redwood, a nurse practioner, decided to become an advocate, speaking at events and publishing papers about thimerosal and autism.
The uproar over a potential link between thimerosal and autism came as a surprise to Orenstein and colleagues.
“Mercury itself had never been implicated as a major cause of autism,” Orenstein said. “But this was a major, major concern.”
It led to a number of studies of the issue, including a 2004 assessment by the Institute of Medicine (now known as the National Academy of Medicine) that concluded “the body of epidemiological evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism.” It made the same conclusion for MMR vaccines and autism.
A 2010 study by the CDC also found no link. And “even after thimerosal was removed from almost all childhood vaccines, autism rates continued to increase,” the agency noted, “which is the opposite of what would be expected if thimerosal caused autism.”
Still, those who continued to push the disproven autism connection included Kennedy, who published a book in 2014 called “Thimerosal: Let the Science Speak.” Its subtitle calls for the “immediate removal of mercury – a known neurotoxin – from vaccines.” It rejects the findings of the 2004 Institute of Medicine report and warns that millions of children in the US and around the world “appear to be at risk of injury from the thimerosal in vaccines.”
Thimerosal is still present in “a small percentage of flu vaccines, confined to multidose vials,” according to a post from the Vaccine Integrity Project, a group focused on countering vaccine misinformation that was started at the University of Minnesota’s Center for Infectious Disease Research and Policy, or CIDRAP.
The group suspects that thimerosal is included on ACIP’s agenda this week – with a presentation by Redwood and a vote by the committee – “to put greater focus on and generate more public discussion about vaccine risk.”
CDC staff also posted its own review of the data, citing nearly two dozen studies showing “the evidence does not support an association between thimerosal-containing vaccines and autism spectrum disorder or other neurodevelopmental disorders.”
During her Senate Health, Education, Labor and Pensions committee confirmation hearing on Wednesday, Dr. Susan Monarez, President Donald Trump’s pick to lead the CDC, said, “I have not seen a causal link between vaccines and autism.”
A fateful decision
The decision to remove thimerosal from most vaccines, despite no evidence of harm, had other consequences. At the same time the FDA made its request to vaccine makers, US health authorities advised that babies born to mothers known to be negative for hepatitis B not receive a shot for that virus at birth, but at two months to 6 months of age, as thimerosal was phased out.
But about 10% of hospitals “suspended use of the hepatitis B vaccine for all newborns, regardless of their level of risk,” wrote Dr. Paul Offit, a vaccine scientist at the Children’s Hospital of Philadelphia and a member of the FDA’s outside advisory committee on vaccines, in a 2007 perspective piece in the New England Journal of Medicine. “One three-month-old child born to a Michigan mother infected with hepatitis B virus died of overwhelming infection.”
Orenstein looks back on the decision to remove thimerosal as a hard one.
“The fear would be keeping it in there, doing a study over two or three years and then it showed harm, and lo and behold, for three years, we used this vaccine and this component was harmful,” he said. “Since we didn’t know what the results would be of any of the studies at the time, we thought it better to just get it out of there.
“The autism issue,” he added, “didn’t play any role in the initial decision.”