The ever-changing theories of vaccines causing autism: Will they ever stop?

Shin

As a Malaysian, I’m surprised that Malaysia is one of the top countries whose people believe vaccines cause autism (Figure 1). Perhaps we are just not as vocal in voicing this issue, giving the illusion that vaccine hesitancy isn’t prevalent here.

The Ipsos Mori Perils of Perception Survey conducted 29,133 interviews across 38 countries in 2017. They revealed that 8–44% of people believed vaccines caused autism in children, 23–63% were unsure, and only 20–62% did not believe it. If you average them, nearly 6 in 10 people worldwide were unsure or believed that vaccines cause autism (Figure 1).

No wonder the World Health Organization (WHO) named vaccine hesitancy as one of the top 10 threats to public health in 2019.

<img src="https://cdn-images-1.medium.com/max/1000/1*J2_ILDxo1Yui9YzZCwpeXg.png" style="width:100%;border-radius:10px;margin-top:0" data-caption="Figure 1. Ipsos Mori Perils of Perception Survey (2017) on vaccines and autism." data-credit="ipsos.com" data-externalurl=""/>
Figure 1. Ipsos Mori Perils of Perception Survey (2017) on vaccines and autism.Photo byipsos.com

Why do people still believe that vaccines cause autism? As a science graduate, I was under the impression that this belief has been widely debunked. But I didn’t read into the details, and perhaps there might be a reason for this belief to sustain to this day.

A backdrop on autism

Autism spectrum disorder (autism) is a life-long neurodevelopmental condition that occurs in childhood due to certain brain changes. It affects 1–2% of children worldwide, about 4-times more often in boys than girls, likely due to how different sex hormones affect brain development.

The main symptoms are impaired social communication and restricted, repetitive behaviors, which are problematic enough to impair daily activities. People with autism may also face delayed developmental skills in language, movement, cognition, and behavioral and emotional control.

Only with the publication of the Diagnostic and Statistical Manual of Mental Disorders, third edition (DSM-III), in the early 1980s, was autism professionally defined. Before that, autism was thought of as childhood schizophrenia, mental retardation, or mere bizarre behaviors.

The cause of autism remains unclear. A combination of genetic, sex, maternal, childbirth, and environmental factors are known risk factors of autism, but the precise contribution of each factor is still ambiguous.

How the scientific basis for the autism-vaccine link started

This autism-vaccine belief began with a 1998 scientific paper, which, though retracted in 2010, still prevails as the founding proof of vaccines causing autism. Let’s see what the 1998 paper has to say.

Andrew J. Wakefield, a former physician, and colleagues had their paper, “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children,” published in The Lancet in 1998, which was retracted as late as 2010. Wakefield was the lead investigator of the paper. And The Lancet is a highly prestigious journal to this day.

The paper was a case series of 12 children with a history of developmental disorder (loss of acquired skills) and intestinal symptoms (diarrhea, abdominal pain, bloating, and food intolerance). Several tests were performed, such as vaccination history, bloodwork, ileocolonoscopy, brain scans, and neuropsychiatric assessments.

A history of the MMR (mumps, measles, and rubella) vaccine was identified in eight of the children before their behavioral problems began. Five of them had an early adverse reaction to the vaccine, such as rash, fever, delirium, and convulsion). And the average time from vaccination to the occurrence of behavioral symptoms was 6.3 days (range: 1–14 days). The MMR vaccine was thus linked to autism and other developmental conditions by either the child’s physician or parents.

Next, ileocolonoscopy revealed several abnormalities in the intestines, such as hyperplasia (tissue enlargement), loss of vascularity, and infiltration of inflammatory immune cells.

Wakefield et al. then cited the opioid excess theory of autism first proposed in 1979, where opioid peptides produced from the metabolism of gluten and casein are leaked into the bloodstream due to a leaky gut. Such opioid peptides then act on opioid receptors of the brain, altering neurotransmission and causing autistic symptoms.

Wakefield et al. also cited Thompson et al.’s study in 1995, which reported higher rates of inflammatory bowel disease in individuals who got the live measle virus vaccine compared to those who didn’t.

Linking the two led Wakefield et al. to conclude that the MMR vaccine inflames the intestines, resulting in a leaky gut and leaked opioids, which dysregulate brain neurotransmission and cause autism.

However, the opioid excess theory of autism — which forms the crux of Wakefield’s vaccine-autism link — was discredited in later years.

At least two studies from the U.K., in 2007 and 2008, found no differences in urinary opioid markers between children with and without autism. “These findings are counter to the putative mechanism of the leaky gut syndrome,” authors of the 2008 study wrote. “There is now a large body of work which refutes the theory and cannot replicate the findings.”

As follows, a 2009 systematic review of 14 studies from the U.S. did not support the use of gluten-free or casein-free diets (GFCF) in treating autism. “The data from these studies do not support the Opioid-Excess Theory,” the review authors wrote. “Until conclusive evidence is found in support of GFCF diets, restrictive diets should only be implemented in the event a food allergy or intolerance is detected.”

If the opioid excess theory of autism is invalid, the presumed mechanism of the MMR vaccine causing leaky gut and subsequent autism also becomes invalid. Now, the causative link between the MMR vaccine, inflamed and leaky gut, and autism crumbles.

Even Thompson et al.’s (1995) paper that Wakefield et al. relied on was flawed. Thompson et al. reported higher rates of inflammatory bowel disease in children who received the live measle virus vaccine than children who didn’t. But scientists had criticized that the unvaccinated children (controls) came from a different cohort — from a child-health study conducted before measles vaccines were available. Recruitment and follow-up methods, as well as baseline characteristics, were different between the two cohorts, rendering their comparison invalid. Plus, Wakefield himself co-authored this study.

Moreover, Wakefield et al.’s 1998 paper was a case series of 12 children. A case series is just a compilation of case reports, which by themselves are weak evidence. By right, case series or reports serve to generate new hypotheses for further studies in larger cohorts. After the 1998 paper was published, Wakefield refused to conduct additional studies to support his findings, despite being aware of the allegations against his paper.

In later years, more studies were conducted on the vaccine-autism link, finding no association whatsoever between the two. In one of the latest studies, scientists followed 657,461 children born from 1999 through 2013 in Denmark. This nationwide study revealed similar autism incidence between MMR-vaccinated and -unvaccinated children. This outcome was not influenced by autism-related risk factors or other childhood vaccinations.

But the greatest offenses Wakefield committed were data manipulation and child abuse.

Brian Deer, a British investigative journalist, exposed that the children’s accounts in the 1998 paper were inconsistent with medical reports and parent interviews (Figure 2). For instance, Wakefield et al. reported a range of 1–14 days in which autism occurred after MMR vaccination. But separate investigations revealed that some of the children had autism before vaccination, and some developed autism as late as 6 months after the MMR vaccine. Some children were not even diagnosed with autism.

Deer further uncovered that Wakefield filed a patent for single vaccines against measle virus (rather than the MMR combination) in 1997, on the basis of a safer vaccine, which is only safer if the MMR vaccine is dangerous. Wakefield also received nearly half a million pounds from lawyers to support the case that vaccines cause autism. These are major financial conflicts of interest that Wakefield concealed.

Aside from financial gains, Deer also found that Wakefield breached ethical issues by performing invasive procedures on the children, such as ileocolonoscopy, lumbar puncture, and MRI brain scan, without approval from the ethics committee. Some of the children were screaming and held down as the procedures were forced on them.

<img src="https://cdn-images-1.medium.com/max/1000/1*JGPax_pD4RN6AcDxJ0zAgA.png" style="width:100%;border-radius:10px;margin-top:0" data-caption="Figure 2. Summary of research misconduct (misreporting and manipulation) by Wakefield et al. in their 1998 paper in The Lancet." data-credit="Deer 2011" data-externalurl=""/>
Figure 2. Summary of research misconduct (misreporting and manipulation) by Wakefield et al. in their 1998 paper in The Lancet.Photo byDeer 2011

Why the vaccine-autism link prevails to this day

It took 12 years for Wakefield et al.’s (1998) paper to be retracted. Many were disappointed at the painfully slow process. And the damage done along the way is massive and irreversible.

MMR vaccine uptake declined right after the 1998 publication and remained so for years thereafter. To this day, MMR vaccine hesitancy remains undeterred, as evident in the 2017 Ipsos Mori Perils of Perception Survey, nearly 6 in 10 people across 38 countries were unsure or believed that vaccines cause autism (Figure 1). In 2021, a record high of nearly 40 million children were not fully vaccinated against the measles virus, partly due to pandemic disruptions and vaccine hesitancy.

As a result, measles — being a highly contagious and potentially fatal virus — still kills more than 200,000 people annually, mostly children.

Despite the widespread awareness that the 1998 paper of Wakefield et al. was fraudulent, autism-vaccine belief prevails for many reasons, one of which is that anti-vaccine theories kept evolving.

Now Wakefield has ditched the leaky gut or opioid access theory for thimerosal (a mercury-based vaccine preservative) poisoning, alongside other questionable scientists. But multiple lines of research did not support any association between thimerosal and autism. Thimerosal contains ethylmercury that human tissues eliminate quickly, which can’t accumulate in the body like methylmercury found in fish and shellfish.

Next, another type of vaccine adjuvant, aluminum, was blamed for causing autism, based on reports finding elevated aluminum levels in the brain of children with autism. As most children are vaccinated, the vaccine was assumed to be the source of the increased brain aluminum. But no credible evidence has substantiated this assumption. In fact, aluminum exposure from dietary sources (such as breast milk and formula) is about the same as all the vaccines an infant normally takes in the first year of life, and the total aluminum exposure is still far lesser than the toxicity limit.

But the only plausible vaccine-autism link is arguably the Hannah Poling case in 2008. Hannah was 19 months old and healthy when she received five vaccines in one day due to prior delays. Two days after vaccination, she developed lethargy, irritability, and fever. She then faced developmental delays for the upcoming months and years and was diagnosed with autism and encephalopathy related to a pre-existing mitochondrial disorder.

Her parents sued the government for compensation under the Vaccine Injury Compensation Program and won, which the anti-vaccine movement used as legal proof that vaccines cause autism.

Hannah’s case was actually published as a case report in 2006, with her father, Jon S. Poling, MD, Ph.D., a neurologist, being the lead author. In this paper, Poling and other scientists argued that mitochondrial disorder compromised the cell’s energy levels. Coupled with excessive immune activation, be it from vaccination or infection, the resulting oxidative stress generated may overwhelm the cells. As the brain is highly metabolically active, it may be the first organ to be affected in this manner.

Poling et al. ran further analyses in their paper. They compiled clinical data on 159 patients with autism and 94 patients of a similar age with other neurological disorders, and compared the patients’ biomarker profiles. Higher levels of aspartate aminotransferase in the autism group were noted (46% vs. 22% of patients). Creatine kinase levels were unusually high in the autism group too (47% of patients), but this data was lacking from the control group. This led to the conclusion that almost half of the autism cases also have underlying metabolic abnormalities.

But other experts highly doubt Poling et al.’s arguments for many reasons:

  • For one, mitochondrial genetic disorders are incredibly rare, with an estimated incidence of 1 in 5000. The claim that almost half of autism patients have a mitochondrial disease appears misleading, which may or may not stem from an underlying genetic mutation.
  • Second, encephalopathy can produce neurological symptoms similar to autism. As a result, some experts argued that Hannah’s case wasn’t the typical autism case and thus isn’t generalizable.
  • Third, mitochondrial diseases are caused by gene mutations. So, “there is no way a vaccination can cause a mitochondrial disease,” said Salvatore DiMauro, MD, professor of neurology.
  • Fourth, winning the Vaccine Injury Compensation Program may not indicate actual vaccine injury. For instance, Dorothy Werderitsh won compensation for the hepatitis B vaccine she believed caused her multiple sclerosis. But hepatitis B vaccine neither caused nor exacerbated multiple sclerosis in several controlled cohort studies.
  • Fifth, a case report by itself can’t prove cause and effect. No solid evidence has shown that mitochondrial dysfunction drives autism, mainly due to the scarcity of research in this area. So, the scientific basis of the vaccine-mitochondrial-autism link is weak.

Overall, “…this was not a case of vaccines causing autism,” as Rahul K. Parikh, MD, Ph.D., associate professor of medicine, put it well. “Rather, this is a case where the court deemed it plausible that vaccines aggravated an underlying disease caused by bad mitochondria, and that some of the symptoms Hannah showed were similar to autism.”

So, it seems plausible that vaccinations may play a role in Hannah’s developmental disorders: encephalopathy and autism-like features. But strict conditions must be met for a case like Hannah’s to occur. You need five vaccinations in a day and a pre-existing rare mitochondrial genetic disease. And even then, the vaccines may only be involved in aggravating the disease process, not causing the disease. Not to mention that it could have been infections that triggered Hannah’s developmental downfall, as her father admitted in his published case report of her daughter.

“There is an incredibly small but real chance that a vaccine could aggravate an underlying mitochondrial disorder, which has been linked to regressive autism in a miniscule fraction of children,” Bobby Duffy, professor of Public Policy, said it well. “There are US court rulings [like Hannah’s case] that we could legitimately take as evidence of this being a hazard, but they are vanishingly rare, and the risk is therefore effectively non-existent. But that is a difficult point to communicate.”

In the end, the vaccine-autism belief prevails to this day because people will always come up with reasons to blame the vaccine, even if the reasons are not scientifically sound. In an unfair situation when a precious child develops autism, it’s human nature to seek justifications for the misfortune. Yet, despite decades of research, the precise cause or trigger of autism remains unknown and may not exist given that autism is a multifactorial disorder. Vaccines are an attractive target to blame because a large community already shares the same sentiment — that big pharma will do anything for profit, including deception. But little did they realize that Wakefield and others are in it for the profit (and fame) too.

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