by William J. Walsh, PhD, in chemical engineering from Iowa State University; researcher, group leader, and section head at Argonne National Laboratory for over 20 years; holder of six patents and author of more than 200 scientific articles and reports; volunteer in Illinois prisons for almost 20 years; and founder in 1974 of the Prisoner Assistance Project. In 1981, the United Way named him "Prison Volunteer of the Year" for metropolitan Chicago. In 1989 he founded, was the first president, and is now the senior scientist of the Health Research Institute and the Pfeiffer Treatment Center in Warrenville, Illinois. He has made numerous presentations on his research at institutions such as the American Psychiatric Association, the U.S. Senate, the Society for Neuroscience, and the National Institutes of Mental Health. The Pfeiffer Treatment Center is a not-for-profit outpatient clinic specializing in treatment of behavior disorders, learning disabilities, attention deficit disorder (ADD), autism, depression, bipolar disorders, and schizophrenia. Their web page address is: www.hriptc.org
Autism was first identified in the early 1940's by Leo Kanner, and incidence was initially believed to be about one in every 10,000 births. Incidence estimates steadily increased over the next 50 years and by 1990 the autism rate had risen to one per 1,000 births. Since 1990 there has been a shocking explosion in autism incidence and recent California studies indicate a rate approaching one per 100 births.
Autism has a strong genetic component, with 60% concordance in identical twins reared apart. However, the fact that this concordance isn't 100% suggests that environmental factors are also involved. Two years ago we met a pair of 38-year-old identical twins who were strikingly different. One brother was a successful businessman and community leader, but the other was severely autistic, mute, heavily sedated, and confined to an institution. Since our national gene pool hasn't undergone radical change, the autism epidemic must be a result of worsening environmental factors.
. . . MT proteins regulate Cu and Zn levels in blood, detoxify mercury and other heavy metals, assist immune function, enable breakdown of casein and gluten proteins, and assist in neuronal development.
Another change in the past 50 years has been the increasing incidence of "regressive autism". In 1950 most children diagnosed with autism exhibited clear symptoms of the condition soon after birth. Today, most autistic children experience normal development until about 20 months of age, followed by a sudden and horrifying decline. Countless families report that the same child that at 18 months of age was happy, singing, beginning to talk, and charming his/her grandparents-within weeks had transformed into a mute, unhappy child who shunned social contact and engaged in odd repetitive movements. The diagnosis of autism is often accompanied with a shocking prognosis: That the condition is incurable, the child may never speak again, and that placement in an institution might be a good idea. At present autism rates, about 40 U.S.A. families receive this news every day.
The Pfeiffer Treatment Center (PTC) began accepting autism-spectrum disorder (ASD) patients in 1994, and by 1999 had studied and provided nutrient therapy to more than 700 ASD children. An open-label outcome study in 1995 revealed that 85% of families reported significant improvements in autism symptoms following PTC chemistry-normalization therapy. Unfortunately, only a few of these children improved to the degree that they were no longer autistic. Most of the parents expressed satisfaction and gratitude for the partial improvements achieved, but my staff and I were far from satisfied since autism was still present in most of these patients.
In 2000, Dr. Bernard Rimland invited me to a one-day "think tank" in New Jersey, which was attended by about 45 autism researchers and clinicians. The participants included many of the big names in the autism field including Rimland, Wakefield, Pangborn, Bradstreet, McGinnis, Megson, Reichalt, Baker, Edelson, Bock, Holmes, Horvath, and Shattock. A microphone was passed around and each attendee summarized the advances they had made in research or therapy methods. I learned many things at this meeting, but was especially surprised to discover that the Pfeiffer Treatment Center had the largest number of ASD patients of those present and also the largest collection of chemistry data for this disorder. I went back to Illinois determined to create a computerized database, which might reveal some of autism's secrets.
In June 2000, three college interns and I (led by Jeffrey Tarpey, medical student at St. Louis University) computerized the chemistry results for 705 PTC patients with a presenting diagnosis of autism-spectrum disorder. Using the Diagnostic and Statistical Manual (DSM-IV), subjects with questionable diagnoses and patients with co-morbidity for seizures, serious head injury, depression, schizophrenia, Tourette's syndrome, and birth anoxia were excluded. The remaining 503 patients comprised the test population for this study:
Between 90 and 160 separate chemical analysis results from blood, urine, and tissues were available for each patient, and the resultant database included more than 75,000 separate chemical assays. We used this database (a) to measure the incidence of specific chemical imbalances and (b) to search for distinctive biochemical differences between patients with classic autism, Asperger's disorder, and PDD with autistic features. It was immediately evident that most of the autism-spectrum patients exhibited severe chemical imbalances. However, no significant differences between the three autism phenotypes were found, despite the great differences in symptoms.
In our initial database study, we found abnormal levels of copper (Cu) and zinc (Zn) in blood (p.0001, meaning the probability of this result occurring by chance is less than 1 in 10,000). These abnormal levels indicate a failure of the metallothionein (MT) protein system to fulfill its role in regulation of these metals. MT proteins are very versatile and are involved in other important functions in humans. In studying more than 3,000 published articles on MT proteins, we discovered that virtually all of the classic features of autism could result from a genetically weakened MT system. For example, MT proteins regulate Cu and Zn levels in blood, detoxify mercury and other heavy metals, assist immune function, enable breakdown of casein and gluten proteins, and assist in neuronal development. These data strongly suggest a universal MT disorder in autism-spectrum patients. These findings were reported1 at the May, 2001 annual meeting of the American Psychiatric Association and were the subject of a Jim Lehrer PBS newscast.
There are four general classes of MT protein: MT-I and MT-II are found in cells throughout the body, with MT-III restricted primarily to the brain, and MT-IV to squamous epithelial cells in the upper gastrointestinal (G.I.) tract. MT functioning involves:
Since MT is directly involved in neuronal development and maturation of the brain, the timing of environmental insults is critically important. Temporary disabling of MT function during a specific stage of brain development (e.g., the speech center) may result in an enduring disability in this area. Multiple insults can result in multiple disabilities. If serious toxic insults are avoided until after age three, the brain and G.I. tract may have sufficiently matured so that autism is no longer possible.
Since our national gene pool hasn't undergone radical change, the autism epidemic must be a result of worsening environmental factors. . . . Today, most autistic children experience normal development until about 20 months of age, followed by a sudden and horrifying decline.
Researchers studying Wilson's Disease have found that MT can be disabled by a systemic overload of copper. Other conditions with the potential for disabling MT include (a) overloads of mercury or other toxic metals, (b) severe zinc deficiency, (c) abnormalities in the glutathione redox system, (d) cysteine deficiency, and (e) malfunction of metal regulating elements (MRE*s).
MT proteins have been the subject of intensive research and the mechanisms of formation and utilization are now well understood. This information provides a roadmap for treatment of persons with a compromised MT protein system. After autism onset, MT proteins may be chronically contaminated with excessive amounts of copper, mercury, and other toxic metals, which can weaken normal MT activity and can have an adverse effect on learning, socialization, behavior control, and immune function.
The Pfeiffer Treatment Center (PTC) has developed a nutrient therapy to promote MT protein activity in the G.I. tract, brain, and elsewhere. This protocol is based on 3,000 published articles describing MT synthesis, activation, and redox mechanisms. A total of 22 nutrients that enhance MT were identified and tested in informal clinical trials involving PTC staff and volunteer autism families.
The scientific literature clearly indicates that most of the body's MT is induced by zinc, with glutathione (a combination of three amino acids: glutamic acid, cysteine, and glycine (GSH)) needed for loading precursor MT with zinc and glutathione disulfide (GSSH) required for redox exchange. Selenium and the GSH/GSSH redox couple enhance (a) delivery of Zn to cells and (b) sequestering of mercury and other heavy metals. The equilibrium constants for binding of functioning MT to heavy metals are remarkably large, with the net result that Zn-MT is a "magnet" for these toxic metals.
MT proteins are composed of 14 amino acids and zinc. Many autism-spectrum patients are unable efficiently to cleave dietary proteins into the individual amino acids needed for MT synthesis. Our formulation includes all 14 amino acids, in the proportion found in MT. The large amount of cysteine required for MT synthesis is supplied in the form of oral glutathione (GSH), which breaks down in the G.I. tract with few side effects.
We found that aggressive zinc loading must precede full-scale MT-Promotion therapy for best results. Each molecule of MT requires 7 atoms of zinc (Zn) for proper functioning. If MT is formed too rapidly at the intestinal mucosa, temporary severe zinc depletion in the peripheral nerves (mostly in the spinal column) and the brain can occur, resulting in irritability and other side-effects.
Our best clinical outcomes have been achieved using a two-phase protocol: (1) preloading with Zn and augmenting nutrients, followed by (2) cautious, gradual introduction of MT-Promotion formulations.
The Pfeiffer Treatment Center (PTC) has submitted patent applications for the MT-Promotion formulations to ensure that they will be widely available at low cost. Because of the need for medical supervision, the MT-Promotion formulations are available by prescription only.
Promotion of the MT protein system is expected to provide many benefits to autism-spectrum patients including (1) elimination of toxic metals, (2) protection against future toxic exposures, (3) normalization of the G.I. tract, (4) improved behavior control, (5) improved immune function, and (6) enhanced development of brain neurons and synaptic connections. The first 5 benefits may be attainable in the first year of treatment, regardless of the patient's age. However, the rate of formation of new synaptic connections declines rapidly with age, and early intervention is critically important for development of speech, cognitive advancement, etc. Great patience is needed in treatment of older children, who can be expected to progress at a relatively slow rate. For example, it may require years for a 10-year-old to achieve the same cognitive progress achieved by a 2-year-old in a few weeks. Behavioral therapies, which shower the brain with impulses and promote neuronal development, are especially recommended in conjunction with MT-Promotion therapy.
In collaboration with a Canadian laboratory, PTC has obtained the world's first MT levels in the blood (red blood cells) of autistic-spectrum patients. The early work has included (1) development of reference normals and (2) comparison of MT levels in autistic subjects and age/gender matched controls. We have consistently found low levels of MT proteins in red blood cells of autistic subjects, compared to controls.
We propose that autism is a disease of metal oxidative stress, resulting from a genetically weakened MT protein system. We also are convinced that autism represents a brain that has not completely matured, rather than a damaged brain, and that MT-Promotion therapies are an effective way to enhance completion of brain organization and synaptic development. Since beginning MT-Promotion therapy, treatment outcomes at Pfeiffer are clearly better than in previous years. It is no longer an unusual event when a child becomes completely free of autism symptoms. However, we continue to experience occasional patients who fail to respond to our therapies.
Actually, I do believe that every
case of true autism involves an environmental insult plus weakened MT function.
The reason for the autism epidemic is a sharp worsening in environmental insult(s).
There is still much work to do, but the mysteries surrounding autism are rapidly
receding.
_____________________________
1Walsh, W., A. Usman, and J. Tarpey, "Disordered Metal Metabolism
in a Large Autism Population," New Research Abstracts, No. NR823,
page 223, American Psychiatric Association Annual Meeting, New Orleans, Louisiana,
May 2001.
Article from NOHA NEWS, Vol. XXVIII, No. 4, Fall 2003, pages 3-5.