Gathering the Evidence: ASD, New Findings, and Public Policy
By James Jeffrey Bradstreet
Issue 115, November - December 2002
Adapted from written supplement to oral testimony before the Government Reform Committee, US House of Representatives, June 19, 2002.
Autism is not a single entity, nor does it have simplistic genetic or epidemiological characteristics; rather, it represents a broad spectrum of clinical disorders that share behavioral and delayed-development features. Autism and its related entities are characterized by delayed neurodevelopment, lack or inappropriate use of language, stereotypical repetitive behaviors, and social withdrawal.
My colleagues and I at the International Child Development Resource Center (ICDRC) have been involved in describing and/or treating this disorder from its biological roots, as opposed to the genetic and psychiatric perspectives. We have medically evaluated and treated over 1,500 children with autism-related disorders. Therefore, our insights contribute primarily to an understanding of the immunology and toxicology of this condition.
In July 2001, I presented the ICDRC data on mercury burden and autoimmunity to the Institute of Medicine (IOM).1 There is a fundamental flaw in the analysis process of vaccine safety. The IOM has undertaken the process of drawing conclusions regarding separate pieces of the actual vaccine schedule when they are, in fact, an integrated event in an individual child's life.
I presented 221 children with autism spectrum disorders (ASD) who showed significantly (500 percent, on average) greater mercury burden when compared to neurologically normal controls. The study was based on routine heavy metal provocation challenge testing similar to that published in Environmental Health Perspectives in 2001.2 I did not try to infer a direct tie to thimerosal. Rather, it was apparent that some possible foundational problem in the metabolism of heavy metals was present in the autistic population. This observation could represent a significant predisposing factor in their vulnerability to mercury when used as a preservative--a point the IOM did not mention. It is also consistent with research regarding sulfur depletion in the presence of persistent viral infections. The literature is replete with references in the case of HIV.3 Rosemary Waring has found marked renal loss of sulfur in autism.4
Of most concern to me in the IOM's treatment of the mercury problems was the almost complete absence of regard for the compounding effect of thimerosal on pre-existing mercury levels. The National Health and Nutrition Examination Survey study from the CDC had already established that perhaps one in ten children is born to a mother with elevated mercury burden.5
Prevalence of ASD
The number of children with autism appears to be greater than previously suspected. Recent hearings of the Congressional Reform Committee revealed a broad consensus that autism spectrum disorders now represent an epidemic of neurodevelopmental problems for our youth. Various recent studies place the prevalence at 57 to 67 per 10,000 children, although older literature places the prevalence at 10 in 10,000 (1 in 1,000).6 However, this figure underestimates the problem for males. Boys suffer from autism at a 4-to-10-fold greater frequency than girls. So the actual problem for male children in this country is more accurately represented as 100 in 10,000 (1 in 100), or greater.
The 1997 US Census disability data reported that 2.4 percent of children ages five and under suffer from developmental delays; clearly many of these are ASD-related issues. Data from California further reveal that the rate of growth of ASD is doubling every four years.7 According to the CDC, 1 in 149 US children have autism.8 (That is the statistic for Brick, New Jersey, but the CDC implies it is consistent with the likely general statistics.) If the current epidemiology of autism is correct, it will affect approximately 1 percent of boys under 18, or an estimated current total of 364,540, as well as approximately 60,000 girls. This is considerably less than the figure of one million reported in Time Magazine's cover story (May 6, 2002), but probably far more accurate.
While no precise studies have attempted to look at the cost of correcting the biological problems associated with ASD, at least one report from England places the custodial costs of ASD in the range of $3 to 4 million per child per lifetime, with a societal cost that would likely be three times the individual cost. The cost of education, medical care, and therapies for behavioral and physical symptoms is staggering. Many of our families report having paid $50,000 per year to care for their child. The Individuals with Disabilities Education Act (IDEA) allows up to $35,000 a year for education of children with autism.
Much of this burden is already being carried by federal and state programs that provide for disabled children. Custodial care for autism can exceed $100,000 a year. The public education system is literally swamped with children. Any survey of public educators will quickly reveal the suddenness and magnitude of the ASD problem. They lack the therapists and trained special educators to deal with the problem, so children with severe disorders receive nominal meaningful intervention. The further loss of potential future earnings from the ASD children who will likely not be self-supporting is impossibly large to calculate meaningfully. Many parents must quit working to care for the child as well. We, as a nation, are therefore paying and will continue to pay an enormous price for this epidemic.
ICDRC estimates the minimal cost, in present value, of caring for those 420,000 existing children with autism at $1,260,000,000,000. So over the next 50 years, a little more than $1 trillion would be required if we stopped creating new cases today. Because autism is doubling every four years, this is likely an overly conservative estimate. The societal cost could easily be $3 to 4 trillion.
Biological Evidence of Causality
The causal relationship of MMR (measles-mumps-rubella) to ASD is not a narrow view held by radical or renegade physicians. Rather, it is sound peer-reviewed science, which, while currently not widely accepted, represents a plausible hypothesis consistent with our observations and the totality of the data. Unfortunately, the present objections to the data are largely based on conclusions drawn from epidemiological studies. The data must be evaluated in their entirety, rather than critiqued bit by bit.
As a clinician treating hundreds of children with specific and measurable biological disorders, I draw very little comfort from the conclusions of epidemiologists. Nor do those conclusions help me explain or treat a child's inflammatory bowel disease or autoimmunity to vital brain components. What I have observed is a definable clinical disorder in which children present with antibodies to a variety of brain components; inflammatory bowel disease; heavy metal burdens, often accompanied by seizures; skeletal maturation delay; and a variety of significant biochemical abnormalities. The children I treat have symptoms consistent with encephalopathy with autistic features.
We are in the process of collecting data and analyzing the trends in our patient population. The case I present here, of my son Matthew, represents both well-established and some very new observations. We have accumulated simultaneous autoimmune and immune studies and viral polymerase chain reaction studies on blood, spinal fluid, and intestinal biopsies. These are combined with comprehensive biological studies. As yet, there are no controls for the viral spinal fluid data, but the immunological data do have controls. What this case means for the rest of the population of children with autism will have to wait for larger studies with reproducibility and necessary controls.
Matthew, who is now eight, seems very typical of many children I have examined over the past five years. He shares similar historical events and laboratory data with as many as 80 percent of our 1,500 patients. He went to term without complication in pregnancy and had an uncomplicated labor and delivery. He presented with an entirely normal first seven months.
At the end of that period he self-weaned, and standard formula was tried. This resulted in reflux and vomiting, so he was changed to predigested formulas with significant reduction in symptoms. The pediatrician noted slight delay in ambulation at 12 months, but in line with maternal developmental patterns. He had a protracted otitis media, which required tube placement by ten months and extended courses of antibiotics.
By 11 months, Matthew was seen in the ER for an acute febrile event not accompanied by seizures. It responded to IV antibiotics and outpatient treatments. Near 15 months he was seen for routine care and vaccinations. He was noted to be on track and developing normally. He received MMR, Hib (Hemophilus influenzae type b), and varicella vaccinations at that visit. Shortly after that he developed tantrums and bizarre behaviors. Then he developed diarrhea and hyperactivity, accompanied by a new symptom: night terrors. With the introduction of essential amino acids and taurine, these symptoms improved somewhat for about eight to 12 months. He then began slipping, with increased hyperactivity and unusual language and behaviors. By age three he was diagnosed as having pervasive developmental delays and tested at the lowest percentile for function in all areas. He started therapies and improved somewhat.
On his fourth birthday the original Wakefield paper was published and at nearly the same time, Matt received his MMR booster.9 (He received the full recommendations of the AAP for vaccinations during the mid- to late 1990s). Shortly thereafter, we noted staring spells, as did the special needs teacher in his title H program. The neurologist diagnosed seizures and tried several medications unsuccessfully. His diarrhea returned and his behavior declined. Several months later we learned about gluten- and casein-free diets, secretin, and intravenous immunoglobulin (IVIG) therapy. After a variety of studies confirmed autoimmunity to his brain, Matthew began IVIG at the suggestion of two department chairs of immunology at different medical schools. The results were dramatic, with improvement in behavior and bowel dysfunction, which had become explosive, with daily soiling past diapers.
The process of regression was not understood by Matthew's pediatrician or any of us in his family. Typically, it was variously dismissed as the result of the terrible twos, having an older sister, being a boy ("They're slower than girls, you know"), several ear infections, food allergies, or an attention deficit hyperactivity disorder.
If we are to believe the experts from the IOM and the Vaccine Safety Committee of the CDC, my son's autism was a coincidental event, and these double-hit MMR events are of no consequence, because MMR has nothing to do with autism. A few years ago, Neal Halsey, the eminent professor of vaccine safety, told the listening audience of CNN that it was natural for me to want to blame something for my son's autism, but that MMR was unquestionably not part of either the timing or autoimmune profile observed. I believe that medicine lacks the luxury of such amazing confidence. However, it seems extraordinarily improbable that Matthew's autoimmune encephalopathy and seizures are not MMR-related. A review of his lab data paints an unmistakable picture, recognizable to any skilled clinician.
Matthew's abnormalities include milk allergy early in life; multiple ear infections; transient gait abnormality up until about one year; rapid decline after each MMR or combination of vaccines with MMR; autoimmunity to myelin basic protein (the insulation of the central nervous system); seizures; immune deficiency with protracted low lymphocyte levels; inflammatory bowel disease; persistent measles virus genome in that inflammatory bowel disease; persistent measles virus in circulating monocytes; persistent measles virus genome in spinal fluid; antibodies to measles virus in spinal fluid; autoantibodies to myelin basic protein in spinal fluid; elevated ammonia; and low sulfate with resultant high mercury due to a loss of glutathione and cysteine.
So what would reasonable clinicians conclude for Matthew's medical diagnosis? Autism? Certainly not--unless they believed the hypotheses of Wakefield, Singh, and a handful of others who are arguing, as I am, that what we have come to call autism in fact represents a new disorder of immune, viral, and toxic origin.
About the only question left to answer is this: did the viral persistence cause the condition, or did the condition cause the viral persistence? In part, we need to consider the toxicity of thimerosal and Matthew's early gait disorder. Thimerosal becomes a neurotoxin as soon as it dissociates and liberates ethyl mercury. The levels of mercury obtained in the vaccine likely combined with environmental mercury from various sources to precipitate the early motor/coordination/gait problems. Researchers at the University of Florida have published their findings regarding early movement disorders as a predictor of future risk of autism.10 This may well be an association with the subtle effects of mercury, although that was not their conclusion. I believe we can assume the inherent "chicken or egg" question.
The implications of these findings could have incredible potential impact on public health policy and the future acceptance of voluntary vaccines by parents for their children. We desire safer vaccines and safer administration of vaccines, but we fear that a lack of government response to the concerns of researchers and parents will result in lowered overall immunity to numerous preventable disorders, because parents will reject some of the vaccines in their current forms. The request for a safer MMR vaccine was also presented by Imani and colleagues at Johns Hopkins.11 So we do not feel alone in our understanding of the apparent immunological flaws of the current trivalent vaccine.
These data are also public knowledge and have been presented at numerous professional and public forums, as well as through publication in mainstream medical literature including Pediatrics, The Journal of Pediatrics, British Medical Journal--Molecular Pathology, The American Journal of Gastroenterology, and recently in a press release from the American Society of Microbiology. Historically, high titer measles vaccine caused more mortality than expected due to the induction of immune deficiency. This caused a reversal of policy, and high titer measles vaccine no longer exists. By their nature, mass vaccination programs are in effect an ongoing open-label experiment. No study can adequately predict the long-term and subtle effects of a vaccine prior to introduction to a group as large as most of the population of our planet.
Unfortunately, as is true of many new discoveries in medicine, the initial reactions are skepticism or rejection. We have seen this historically with H. pylori and peptic ulcer disease, as well as during the emerging literature on AIDS and HIV. Eventually, the early observations in these disorders were proven accurate, medicine adapted, and acceptance became universal. We believe the same is true for mercury, MMR, and autism, despite the present political incorrectness of the findings.
1. Immunization Safety Review: Thimerosal-Containing Vaccines and Neurodevelopmental Disorders (National Academies Press, 2001), 47.
2. H. Frumkin et al., "Diagnostic Chelation Challenge with DMSA: A Biomarker of Long-Term Mercury Exposure?," Environ. Health Perspect. 109, no. 2 (2001): 167-171.
3. See, for instance, R. Breitkreutz et al., "Massive Loss of Sulfur in HIV Infection," AIDS Res. Hum. Retroviruses 16, no. 3 (2000): 203-209.
4. R. H. Waring and L. V. Klovrza, "Sulphation Deficit in 'Low-functioning' Autistic Children: A Pilot Study," J. Nutri. Environ. Med. 2000; 10, no. 1 (2000): 25-32. See also Waring's article in Biol. Psychiatry 46, no. 3 (1999): 420-424.
5. Morb. Mortal. Wkly. Rep. 50, no. 8 (2001): 140-143.
6. Fiona Scott et al., "Brief Report: Prevalence of Autism Spectrum Conditions in Children Aged 5-11 Years in Cambridgeshire, UK," in Autism: International Journal of Research and Practice 2002 (in press).
7. Sandy Kleffman, "Increase in Autism Alarming," Contra Costa Times, posted May 7, 2002.
8. J. Bertrand et al., "Prevalence of Autism in a US Population: The Brick Township, New Jersey, Investigation," Pediatrics 108, no. 5 (2001): 1155-1161.
10. Philip Teitelbaum, Proc. Natl. Acad. Sci. USA 95 (1998): 13982-13987.
11. Farhad Imani and Kelly Kehoe, "Infection of Human B Lymphocytes with MMR Vaccine Induces IgE Class Switching," Clin. Immunol. 100, no. 3 (2001): 355-361.
James Jeffrey Bradstreet, MD, FAAFP, is currently involved in research into the causes of autism with 15 medical schools in 11 countries. He is director of the US division of the Intercontinental Case Control Study of Autism and Its Relationship to Vaccines and serves on the board of directors of the International Child Development Resource Center in Palm Bay, Florida. Dr. Bradstreet and his wife have two children, Elizabeth (10) and Matthew (7). Matthew continues to be Bradstreet's inspiration for helping children and families affected by autism spectrum disorders.
For more information on vaccines see the Mothering Reprint: Vaccines: Mercury, Autism and Chronic Disease