Autism represents itself both diagnostically and functionally as a spectrum of disorders. On one end of that spectrum one could place classic autism and on the other, Attention-deficit Disorder (with PDD and Asperger's Syndrome somewhere in the middle). These terms (or diagnoses) would genetically be referred to as the phenotype (the observed representation of one's genetic makeup). One's actual genetic make-up or genotype was mostly suspect, and without current technological advances it would remain invisible. It is known that despite the combined symptomatology (phenotype ) that presents as autism, different children have different issues. Some children on the spectrum have chronic gastrointestinal problems ( e.g. reflux, abdominal pain, constipation, diarrhea, mal-digestion, mal-absorption), others immune dysregulation ( e.g. allergies, recurrent infections, autoimmune phenomenon), still others present with problems with metabolic abnormalities ( e.g. methylation abnormalities, transulfuration problems, metallothionein dysregulation, detoxification problems) and some have all of these and other physiologic symptoms. Detoxification in and of itself may be at the crux of these failed biochemical pathways; but even if it is, it is not alone in the physiological challenges that affected children struggle with. Despite the fact that an ARI survey of parents showed chelation as the single most effective intervention in affected children, we can not pretend that it is a miracle intervention for all. The dramatic rise in the rate of autism and related disorders without any concordant change in diagnostic criteria led us to look at environmental factors that may have combined within particular genetically predisposed individuals to conspire toward the development of autism (and related disorders). It is the premise, within the DAN! (Defeat Autism Now!) Movement, that these underlying biochemical abnormalities and problems are if not the cause, then significant contributors to the disorder and it is by addressing these biochemical abnormalities at the source that the reversal of autism can become a reality.

Almost all illness results from some combination of environmental effect and genetic predisposition. This in some small way answers the painful question, "Why my child?" Because despite the alarming increases in the rate of autism, which over the last 10 years has been 700% nationwide, many children are not affected. It may be that the same environmental insults do not cause the same illness in children with different genetic; and therefore biochemical, make-up (e.g. one person with exposure to mercury might detoxify it completely; another might be unable to and develop neuropsychiatric problems, while yet another might develop thyroid problems). One area that is offering new insight into the reasons "why" is in the field of Genomics. It is now possible to assess weaknesses in a person's genetic make-up that would reflect their ability to clear heavy metals from their bodies or make the enzymes crucial for detoxification. By supporting these "weak" pathways with the necessary enzymatic co-factors, it is possible to ')ump start" these sluggish biochemical reactions. Of course, the 'map is not the terrain', and

genetic weakness in a particular area (and concordant support of that enzymatic pathway) will not always dictate a successful therapy. The dysfunction of these pathways can lead to a buildup of by-products or toxins (e.g. Mercury and other heavy metals) and this "build-up" will poison the very pathway that was designed to clear the toxins. This is why it can become necessary to

-cleanse through some kind of formal detoxification, and precisely the reasoning behind a comprehensive approach and the need for an "integrative" solution to the problems we find in our kids.

Because children on the spectrum have such tremendous biochemical individuality, it is necessary that the interventional and diagnostic approach to them is equally diverse. In doing this the approach must be a combination of both empiric and evidence-based medicine. Empiric therapies make use of clinical experience and are in some ways less scientific. There is not a specific test available to justify a particular intervention; however it might be 'time-honored' and have little risk associated with it and significant benefits. A good example of this might be a dietary intervention like a casein and gluten-free diet. There is scientific evidence that indicates that it has value, but no validated test that tells us that it is necessary in a particular case. Evidence based therapy depends upon specific testing and treatment is based upon redressing abnormal lab or test values. An example of this might be an abnormally high ammonia level in the blood. High ammonia levels are know to cause neuropsychiatric symptoms and treatment would be directed toward lowering the ammonia levels with an end-point of improving cognitive ~ function. Because autism's origins are as yet not perfectly defined and are indeed different in iJi! different children, then it would make sense that the clinical approach would need to be an intelligent and measured balance of both empiric and evidence-based therapies that would differ from child to child. Physicians must address the underlying causes physiologically as a means of reversing the neuropsychiatric symptomatology .

There are consistent trends in the biochemical make-up of autistic spectrum children. There are consistently low sulfur amino acids, plasma sulfur, reduced glutathione, abnormally low carnitine levels, zinc & selenium plasma levels. We see elevated blood ammonia levels, ratios of copper to zinc in the serum, microbial metabolites in the urine, brain autoantibodies in serum, titers for virus immunoglobulin especially measles virus, and abnormally high elemental toxins on provocative challenge (e.g. mercury, lead, arsenic, cadmium and aluminum). It is in the vein of these biochemical abnormalities that treatments are tailored: orthomolecular supplementation for amino acids, vitamins, minerals and macronutrients; immune therapy for autoimmune disease and immune dysregulation; detoxification for abnormal metabolites and heavy metals and naturopathic and allopathic interventions to address the physiologic symptoms and disease processes that result from these abnormalities (e.g. antifungals and antibiotics to address infection~ antihistamines, mast cell stabilizers and leukotriene inhibitors to address allergy and the inflammatory cascade that may result~ enzyme therapies to aid in digestion and concurrent nutrient absorption). What we have learned is that regardless of the end-point for symptom resolution is that our approach must be integrative, as the challenges are all interrelated. Detoxification is the ultimate example of this, as we are hamstrung in our ability to pull poisons from our kids before we have established a requisite measure of balance to their gut ecology , their diet, their immune function and their biochemistry. And in effect these balancing acts are, in fact, part of the detoxification process. Understandably, it is chelation that carries our banner especially because of its potent and protaganistic role; but we must not forget the need for r balance in the healing process.

The approach is wholism, addressing the whole patient, from biochemistry to physiology to psychology to spirituality and everything in between. Autistic spectrum disorder is a cataclysm, where body systems and biochemical pathways fail. Biomedical interventions and the DAN! .Model endeavor to synergistically restore, rebuild and support the damage and the inherent weaknesses that are present so as to normalize the body's function and allow the body's innate healing capacity to take over.