Autism

Doing Your Homework, Plus 7 Treatment Strategies

The good news for parents of children with autistic spectrum disorders is that there's no need to reinvent the wheel; whatever your question, many concerned parents and dedicated clinicians have been there before you. Here's how to tap into the latest thinking.

RESEARCH

Your first stop is the Autism Research Institute, autism.com, where you can order a copy of the DAN protocol. Also visit physician Jeff Bradstreet's International Child Development Resource Center at gnd.org

READ

Several books describe unconventional approaches to treating autism with an emphasis on nutrition. Three of the most popular include Karyn Seroussi's now-classic book, Unraveling the Mystery of Autism and Pervasive Development Disorder: A Mother's Story of Research and Recovery, Children with Starving Brains: A Medical Treatment Guide for Autism Spectrum Disorder by Jaquelyn McCandless,M.D., and Facing Autism: Giving Parents Reasons for Hope and Guidance for Help by Lynn Hamilton.

FIND A DAN PRACTITIONER

The biomedical approach to treating autism is far too complicated to tackle on your own. To find a doctor or practitioner qualified to supervise treatment, use DAN's state-by-state listing, available at cgiworker.com/danlist/danlist. Once you've found a practitioner, he or she can test your child and then help you find the most appropriate options.

Here are a few promising treatment strategies:

1. Test Before Treating. A series of blood, urine, stool, and sometimes hair tests will reveal a great deal about the toxins your child has been exposed to, the condition of his or her digestive system, and the nutritional deficiencies and metabolic imbalances your child most likely suffers from.

2. Deal With Diet. Kids with autistic spectrum disorders appear to benefit significantly from specialized diets. For guidance on the popular glutein-free casein-free (GFCF) diet, or specific carbohydrate diet, visit gfcfdiet.com, or the Autism Network for Dietary Intervention (autismndi.com), or breakingtheviciouscycle, a website built around the work of nutritionis Elaine Gottschall.

3. Supplement with Vitamins and Minerals. To treat the metabolic issues that accompany, and perhaps underlie autism, you'll need a host of vitamins and minerals, including magnesium, zinc, B vitamins, omega-3 fatty acids, and vitamin A. Showing particular promise is a so-called quintet of metabolic enhancers, including tri-methyl-glycine, folinic acid, glutathione, allithiamine, and methyl B-12.

4. Experiment with Enzymes. In addition to specialized elimination diets, many parents trying the DAN protocol report benefits from digestive enzymes, including those made by Houston Neutraceuticals (houstonni.com) and EnZymAid by Kirman. A useful resource is Enzymes for Autism and Other Neurological Conditions by Karen DeFelice. She also has a website at Enzymestuff.com.

5. Detoxify. DAN practitioners favor chelation therapy as a way to rid the body of contaminants; some parents prefer the gentler route offered by homeopathy. Amy Lansky describes the dramatic improvement her son Max underwent, for instance, after undergoing homeopathic treatment in Impossible Cure: The Promise of Homeopathy.

6. Consider Growth Factors. These substances, such as IGF-1 developed by Barbara Brewitt, are showing promise in treating some children with autistic spectrum disorders. For more information, visit Biomedcomm.com.

7. Keep Up. New treatments and products are being developed all the time; stay abreast of the latest research by visiting the DAN website (autism.com) and attending autism conferences.

Is Autism a G-Alpha Protein Defect Reversible with Natural Vitamin A?

by Mary N. Megson, M.D., F.A.A.P.

Autism may be a disorder linked to the disruption of the G-alpha protein, affecting retinoid receptors in the brain. A study of sixty autistic children suggests that autism may be caused by inserting a G-alpha protein defect, the pertussis toxin found in the D.P.T. vaccine, into genetically at-risk children. This toxin separates the G-alpha protein from retinoid receptors. Those most at risk report a family history of at least one parent with a pre-existing G-alpha protein defect, including night blindness, pseudohypoparathyroidism or adenoma of the thyroid or pituitary gland.

Natural Vitamin A may reconnect the retinoid receptors critical for vision, sensory perception, language processing and attention. Autism spectrum disorders have increased from 1 in 10,000 in 1978 to 1 in 300 is some US communities in 1999. Recent evidence indicates that autism is a disorder of the nervous system and the immune system, affecting multiple metabolic pathways.

Autism has been defined by DSM-IV criteria as a childhood behavioral and neurological disorder with onset prior to three years of age. Autistic children and adults have qualitative impairments in social interaction and communication, including either a delay in or complete lack of language development. Furthermore, many people with autism engage in restrictive patterns of behavior including rigid adherence to routines and/or repetitive motor mannerisms such as hand flapping (1).

Autistic spectrum disorders have increased from 1 in 10,000 in 1978 to 1 in 300 is some US communities in 1999 (2). Recent evidence indicates that autism is a disorder of the nervous system and the immune system, and it affects multiple metabolic pathways.

This study of 60 autistic children and their families suggests that inserting a G-alpha protein defect, namely the pertussis toxin in the D.P.T. vaccine, (3) into genetically at-risk children causes autism. This toxin separates the G-alpha protein from retinoid receptors. Those most at risk report a family history of at least one parent with a pre-existing G-alpha protein defect, exhibited in disorders such as night blindness, pseudohypoparathyroidism or adenoma of the thyroid or pituitary gland (4).

This hypothesis asserts that treating these children with natural cis forms of Vitamin A may have the effect of reconnecting the hippocampal retinoid receptor pathways that are critical for vision, sensory perception, language processing and attention (5).

Many of these especially vulnerable children have tissue types of HREs DR 3, DR4, and DR5 (6). These particular tissue types form the tightest bonds with blocked RAR and RXR retinoid receptors (7).

Autism is a true developmental disorder. Many of these children are exposed to wheat at nine months, followed by exposure to the measles antigen at 12 to 15 months (8). The human measles antibody that is produced cross-reacts with intermediate filaments, which are known to be important for maintaining tight junctions and gap junctions between cells, gut mucosal integrity and cell to cell communication (10)(11).

Many of these children, who need natural, unsaturated cis forms of Vitamin A found in sources such as cold water fish like salmon, or cod, liver, kidney, and milkfat, are not getting this in the modern diet. Instead, they are dependent on Vitamin A Palmitate, found in commercial infant formula and lowfat milk. Unfortunately, absorption of Vitamin A Palmitate requires an intact gut mucosal microvilli surface at the right PH, in the presence of bile for metabolism (12). However, many of these children already have damaged mucosal surfaces due to unrecognized wheat allergy or intolerances.

The Role of Vaccinations in G-Alpha Protein Defects

When the live viral measles vaccine is given, it depletes the children of their existing supply of Vitamin A (13), which negatively impacts the retinoid receptors. Natural Vitamin A, in the cis form, is important for activation of T and B cells for long-term immune memory to develop (14) and is necessary for natural killer cell function (15). Scrimshaw, et al. (1968) reviewed over 50 studies of infection and nutrition and wrote, "no nutritional deficiency in the animal kingdom is more consistently synergistic with infection than that of Vitamin A" (16).

If artificial Vitamin A Palmitate binds the now free G-alpha protein, it deactivates by 90% the "off switch" for multiple metabolic pathways, involved in vision and cell growth, and disrupts hormonal regulation and metabolism of lipids, protein and glycogen (17). Measles, mumps and rubella titers are either significantly elevated or negative, in spite of one or two doses of the vaccine given to many of these children. Fish oils contain one retinoid metabolite, alpha 14 hydroxyretroretinol that has a role in T-cell activation, vision and growth of lymphoblasts (18). Further research is needed to understand the complete role of these metabolites in the immune system.

At 18 months of age, when the pertussis toxin is added, as "lymphocytosis proliferating factor," it creates a chronic autoimmune monocytic infiltration of the lamina propia in the gut mucosa (19) and may disconnect the G-alpha protein pathways, leaving some G-alpha modulated pathways unopposed. Consequently, the non-specific branch of the immune system is turned on, and without retinoid switching, cannot be down-regulated. The metabolic consequences could be far-reaching.

These 60 children and their families reveal possible consequences of losing the "off-switch" in G-alpha protein modulated pathways through abnormalities in lipid, glucose and protein metabolism in hormone regulation and in oncogene suppression and autoimmune disorders.

Case Studies

Our early experience with treatment with natural cis forms of Vitamin A in Cod Liver Oil (CLO) in these autistic children, followed by stimulation of blocked acetylcholine receptors for neurotransmitters affected with a blockage of G-alpha pathways in the cell, is promising. There are dramatic, immediate improvements in language, vision, attention and social interaction in some of these children, as evidenced by the following case reports.

My earliest evidence came from a ten-year-old boy diagnosed with autism by DSM-IV criteria (20). The patient’s parents suspect he has been reading since age four but his inability to communicate made this unverifiable. Over an eight-year period of regular visits I had never heard him speak. Standardized IQ tests revealed moderate mental retardation. His mother developed night blindness and hypothyroidism in college and had responded well to Vitamin A and thyroid hormone replacement. The patient’s mother’s sister was diagnosed in infancy with gluten enteropathy that had improved on a gluten free diet. She has had lifelong dry eyes and is night blind (treated with amber glasses.)

For these and other reasons I started the boy on cod liver oil (5,000 IU of Vitamin A, given in 2500 IU/b.i.d.) and a gluten free diet. After one week, he began to sit farther from the television and to notice paintings on the walls at home. He had always gone out of his way to follow the sidewalk and driveway to meet the school bus. On Vitamin A, he began to run across the grass directly from the front door to the school bus. After three weeks, he was given a single dose of Urocholine, an alpha muscarinic receptor agonist, to increase bile and pancreatic secretions and indirectly stimulate hippocampal retinoid receptors. It has minimal cardiac effect, is FDA approved, has been used safely in children since the 1970’s for reflux, and does not cross the blood-brain barrier, unlike secretin (21). It stimulates post-synaptic cell membranes via receptors for acetylcholine, a neurotransmitter in the parasympathetic system.

Thirty minutes after administration of the Urocholine, the patient, who was sitting in a chair, swung his feet over the side, pointed to a glass candy jar on my shelf and said, "May I have the red Jolly Rancher® please?" He had read the label on the candy in the clear jar. These were the first words he had spoken in eight years, and the first proof that he could read. We took him outside and he said, "The leaves, the leaves on the trees are green! I see! I see!" When I asked to take his picture he looked at the camera, smiled and waved. When he left the office I said, "See you later." He asked, "What time?"

In this child’s case, after several weeks of treatment with Vitamin A in CLO 3500 IU/day, the Urocholine acted like a switch. When absorbed, he immediately became socially engaged, made excellent eye contact, hugged his mother tightly and said, "I love you so much," looking at her face. At that point we both realized that this child had a blocked pathway. The change in language and social interaction was dramatic and immediate. Yet he reverted to the pre-treatment state of silence when the dose wore off. On lower daily doses of Urocholine (12.5 mg bid) along with the Vitamin A, his language and social interactions have continued to progress, albeit slowly.

I discussed the case with Dr. Bernard Rimland, head of the Autism Research Institute. He called me later to get permission for a mother in Kentucky to call me. She was frantic because her fourteen-week-old infant had stopped making eye contact, began to stare at lights and fans, stopped cooing and laughing and no longer turned to sound after early normal development. The mother reported she was night blind and had irritable bowel syndrome. By mother’s report, the infant was weaned and placed on standard formula, which was tolerated well. An audiological evaluation revealed normal auditory brainstem responses and tympanograms. The child went to a pediatric Ophthalmologist, who stated the child was farsighted. The exam was otherwise normal. The doctor was unable to get the infant to track in daylight, but when he placed an amber screen in front of his eyes he would easily track all objects.

I spoke with the child’s pediatrician who obtained a Vitamin A level. The value was 26 ug/dl (normal is 30-90 ug/dl). I instructed the mother to add 0.85 cc of CLO (Vitamins A/D) of cod liver oil to a bottle that night, and 0.85 cc CLO to a bottle at 11 am the next day. When the baby woke from his nap, he was back to normal, smiling, laughing, turning to sound, and tracking objects. As a developmental pediatrician, I have followed his development. By his mother’s reports, his receptive and expressive language, cognition, fine and gross motor skills are all normal for his age of nine months. He has remained on 0.85 cc CLO without significant increase in his vitamin A and D levels. He has had further immunizations without regression.

In both cases the improvement was so dramatic that it seemed we were dealing with a blocked pathway, presumably in the hippocampus or amygdala, with an intact cortex.

Effects of Blocked Retinoid Receptors

In December 1998, Ron Evans et al., at Cornell, isolated RAR-B and RXR receptors in the hippocampus in mice, which, when blocked, created long-term potentiation and depression of neurotransmission (22). The hippocampal pathways are important in spatial learning and memory. When mice with these blocked receptors were put in a maze, and then the maze was changed, these mice never learned to accommodate for the change. However, both normal mice and blind mice easily learned the new pathway with subsequent trials. Evans reported that these mutations affected cognitive functions such as learning and memory and reports that the mice acted as if "they had significant visual perceptual deficits." (23)

Of note, the hippocampus, on staining and electromagnetic exam, revealed no anatomic abnormalities. Presynaptic and post-synaptic responses were normal (24), so the authors concluded that the changes involved changes in inhibition or potentiation at the cellular level. The authors suggested that lack of retinoid signaling did not affect neuronal development (25).

Six of the autistic children I have tested also have had hypothyroidism. Recently reported was the association of central hypothyroidism when RXR receptors were blocked (26). These RXR receptors are nonspecific members of the superhormone receptor system, and have been identified as calcitonin/secretin, thyroid and retinoid receptors specific for binding with the short carbon chain cis forms of Vitamin A, found in liver, kidney, milkfat and CLO (27).

In the cell membrane, in the hippocampus (28) and retina (29) are G-alpha proteins with RXR and RAR-B receptors that potentiate or depress the signal in a given cell (30). Congenital night blindness is caused by a single protein deletion in G-alpha membrane proteins inside the cell attached to the retinoid receptors which traverse the cell wall, leading to decreased potentiation of the signal (29). Normally, the signal is amplified ten million times from stimulation by the time it exits the G protein coil, providing night vision in conditions of very low light. Gi alpha inhibits cAMP synthesis, closes Ca+ channels and opens K+ channels, while Gs alpha has the opposite effect (30). Both stimulatory and inhibitory G-alpha proteins modulate acetylcholine and adrenergic amines, neurotransmitters and chemokines, all affected in autism (31).

Vitamin A and Urocholine

Autism may be a disorder linked to the disruption of the G-alpha protein and the resulting effects on the retinoid receptors. These cell membrane proteins are coils that modulate sensory input. Cis forms of retinoids may act by replacing these receptors and by easily penetrating the cell membrane for more direct effects on nuclear retinoid pathways.

Many children treated with Vitamin A in CLO for two months followed by Urocholine show an immediate improvement in their autistic behaviors including improved eye contact, ability to socialize, and increased language use. Many have been able to toilet train easily and have begun to sleep through the night. Postganglionic parasympathetic muscarinic receptors innervate the bowel and bladder through sacral roots, and the pineal gland where melatonin is produced, through fibers from the upper cervical ganglia. This may be why the children are able to improve their sleep cycles and to toilet train on Urocholine and natural Vitamin A.

One of the first improvements noted on Vitamin A in CLO in children is the dis-appearance of the "sideways" glance at people and objects. By doing this, these children with poor rod function are getting their best three dimensional view of the object by directing light through the pupil onto the fovea (32), which is off-center in the retina, the area of the greatest intensity of red and green cones and greatest acuity. Improved eye contact is noted almost immediately in the autistic children on Vitamin A.

Importance of Binding Proteins

Cellular retinaldehyde-binding protein is important in transferring retinal from the photoreceptor to the retinal plasma epithelia. This binding protein is found in the retina and pineal gland. The human genome has sequence similarities with yeast SEC14 protein, which stimulates secretory activity of the Golgi apparatus (33).* These Muller cells are Potassium sinks, which are RXR and RAR-B receptors modulated by G-alpha proteins (34). If depolarization here is not "intensified" because of a G-alpha protein defect, this may decrease the stimulus to the brain from the neural retina. This protein binds only the 11-cis and other di and tri cis isomers of retinaldehyde to form a stable complex with opsin, the forms found in CLO (36).

P19 cells are neuron stem cells, which, in their response to their RXR and RAR receptors being stimulated by retinoic acid, undergo cell differentiation. As these cells differentiate, they express characteristics of epithelial cells. Many syndromes with neurocutaneous markers are associated with autism. These cells, upon differentiation, have a small voltage outward current, but when differentiated have large inward sodium, potassium and CA+ currents. As mature cells they synthesize acetylcholine, not catecholamines (37). Urocholine stimulates alpha muscarinic postganglionic parasympathetic acetylcholine receptors. Affected G proteins, trimeric guanine nucleotide binding proteins, rely on signals from protons, hormones, odorants, and neurotransmitters and either decrease transmission, causing less effect when stimulated by hormones, or increase transmission (38). Sensory abnormalities seen in these children may be due to a lack of modulation in signal in the cell membrane, but this warrants further study.

Abnormal Lipid Profiles

Also, there appeared to be a very high incidence of abnormal lipid profiles in the children. These serum values were drawn prior to the administration of Vitamin A in CLO, due to the known effect of retinol and the synthetic retinoids causing hyperlipidemia. Doses of Vitamin A in CLO in our trial are far below minimal supplemental doses required to induce elevations of lipids, especially triglycerides and VLDL. Of note, supplementation with fish oils with eicosapentenoic acid (EPA) and decosahexenoic acid (DHA) has been reported to reduce these lipid levels (39).

Blocked Neurotransmission

For many of these children, autism represents blocked neurotransmission that can be reconnected. Correcting immunodysfunction and their metabolic disorders will be important for prevention of future early heart, endocrine and malignant disorders of endothelial origin.

To quote Alfred Gilman, winner of the Nobel Prize for his discovery of G-alpha proteins, we have been "barbarians at the gate" of cellular function in multiple organ systems (40). These children have been devastated and we have abandoned them and their families from healthcare and rehabilitative services and appropriate educational opportunities.

The far-reaching metabolic consequences may be enormous, with potential links to not only autism, but dyslexia, attention deficit hyperactivity disorder (ADHD), bi-polar disorder, schizophrenia, Chronic Fatigue Syndrome, fibromyalgia, Type II hyperlipidemia, gluten enteropathy, cancer of the mucous secreting glands, and autoimmune disorders including muscular dystrophy and rheumatoid arthritis. S-Adenosylmethionine (SAMe), called a supernutrient, is an enzyme-important in acetylcholine synthesis. Loss of gut mucosal integrity would decrease by 85% gut absorption of CoA, shunting choline into homocysteine production. Increased production of acetylcholine may explain why a continuous dietary source of this nutrient makes people with multiple disorders feel better. Increased serum homocysteine levels have previously been associated with early cardiac disease (41). The incidence of mucous-secreting malignancies in parents and grandparents of the children in the study was 62 cases within 60 families. Cases of adenocarcinoma of the colon alone were seen in 1 in every 4 families when the lifetime risk is approximately 4 percent (42).

The current clinical trial using Vitamin A in CLO vs. placebo in a double blind, cross-over study is necessary prior to a trial using Vitamin A and Urocholine. Data from this trial is important and will have very broad ramifications, including rethinking infant formula composition and timing of immunizations. If this hypothesis is correct, we are one step closer to treatment and prevention of autism.

REFERENCES

1.Wolaich, ML, Felice, M, Drostart, D. The Classification of Child and Adolescent Mental Diagnoses in Primary Care. Elk Grove Village, Ill: American Academy of Pediatrics, 1996: 316-317.

2.Rollens, R. Testimony before the United States House Committee on Government Reform, Aug. 3, 1999. By permission.

3.Farvel, Z, Bourne, HR, Iiri, T. The Expanding Spectrum of G Protein Diseases. N Engl J Med 1999; 340: 1014, 1018.

4.Farfel, Z, Bourne, HR, Iiri, T., p. 1013.

5.Chiang, MY, Misner, D, Kemperman, et al. An Essential Role for retinoid receptors RARß and RXRa in long-term potentiation and depression. Neuron, 1998; 21: 1353-1361.

6.Sporn, M, Roberts, A, Goodman, D. The Retinoids: Biology, Chemistry and Medicine. Raven Press, 1994: 331.

7.Sporn, M, et al., 331.

8.Mandell, GL, Bennett, JE, Dolin, R. Principles and Practice of Infectious Diseases, 4th edn. New York: Churchill Livingstone, 1995: 1523.

9.Cohen, A., Bennett, J. Rheumatology and Immunology, 2nd edn. Orlando:Grune and Stratton, 1986: 442.

10.Sporn, M, et al., 636.

11.Fauci, AS. Harrison’s Principles of Internal Medicine, 14th edn. New York: McGraw Hill, 1998:510.

12.Sporn, M, et al., 231.

13.Sporn, M, et al., 231.

14.Sporn, M, et al. 536-537.

15.Sporn, M, et al. 531-532, 535.

16.Sporn, M, et al.,

17.Berman, D, Gilman, A, Mammalian RGS Proteins: Barbarians at the Gate. J Biol Chem. 1998; 273:1269-1272.

18.Wakefield, A, Murch, S, Anthony, A., et al. Ileal Lymphoid-Nodular Hyperplasia, Nonspecific Colitis And Pervasive Developmental Disorders In Children. Lancet 1998; 351:639.

19.Sporn, M, et al. 536-537.

20.Wolraich, ML, 316-317.

21.Arky, R, Physicians Desk Reference, 52nd edn. Montvale, NJ: Medical Economics Co.; 1997:1759.

22.Chiang, et al., 1353-1361.

23.Chiang, et al., 1359.

24.Chiang, et al., 1356.

25.Chiang, et al., 1359.

26.Sherman, SI, Gopal, J, Haugen, BR. Central hypothyroidism associated with Retinoid X Receptor—selective ligands. N Engl J Med 1999; 340:1075-1079.

27.Sporn, M, et al. 333.

28.Chiang, et al., 1353-1361.

29.Sporn, M, et al., 353.

30.Farvel, Z, et al., 1012.

31.Meisenberg, G, Simmons, W. Principles of Biochemistry, St. Louis: Mosby, 1998:577-594.

32.Sporn, M, et al., 352.

33.Luscher, C, Jan LY, Stoffel, M et al. G Protein Coupled Inwardly Rectifying K+ Channels (Girks) Mediate Postsynaptic But Not Presynaptic Transmitter Actions In Hippocampal Neurons. Neuron 1997; 3:687-695.

34.Zahraoui, A, Touchot N, Chardin, P, Tavitian, A. The Human Rab Genes Encode A Family Of GTP-Binding Proteins Related To Yeast YPT1 And SEC4 Products Involved In Secretion. J Biol Chem 1989; 264:12394-12401.

35.Sporn, M, et al.,356.

36.Sporn, M, et al.,356.

37.Sporn, M, et al., 484-485.

38.Farvel, Z, et al., 1012-1015.

39.Sporn, M, et al., 650.

40.Berman, DM, et al., 1269-1272.

41.Nygard, O, Nordrehaug, JE, Refsum, Ueland, PM, Farstad, M, Vollset SE. Plasma Homocysteine Levels and Mortality in Patients with Coronary Artery Disease. N Engl J Med 1997; 337:

42.Wijnen, JT, Vasen, HFA, Khan, PM, Zwinderman, AH, et al. Clinical Findings With Implications For Genetic Testing In Families With Clustering Of Colorectal Cancer. N Eng J Med 1998; 339:511.

Breakthroughs in the Evaluation and Treatment of Autism

Dear Parents, Friends and Relatives,

Here is an update of my synopsis of the "DAN" Conference (Defeat Autism Now), presented by Dr. Bernard Rimland, Dr. Jon Pangborn, Dr. Sidney Baker and their colleagues. The DAN Conference was formed by Dr. Rimland to bring together the world's foremost doctors and scientist to form an effective protocol to treat Autism. The DAN autism conference had so much important information, that I found it overwhelming, even with my Honors Degree in Biochemistry and my Medical Training as a doctor. It took me about 3 Dan Conferences before I really felt comfortable with all the information. The fourth DAN Conference was finally a breeze. So I spent hundreds of hours to put together my first synopsis of the DAN Protocol in order to help parents grasp what the essentials were. So many changes have occurred that I feel compelled to provide an update.

At this point, I would like to point out that this is not medical advice, even though I am a Medical Doctor. Rather, this is a wish for your child or your loved one(s) to have the advantage of what took us eight years to discover. Please take this as a medical disclaimer. All suggestions here should be done at your own risk. Though, hopefully, the risk is minimal. These protocols are best done with someone who is familiar with the DAN Protocol, (a DAN Doctor). As I mentioned in my website, www.miriamjangmd.com, I am set up to treat Autistic individuals anywhere in the United States or Canada. Please feel free to contact us to treat your Autistic child, if you wish. In this synopsis, I will also be including some information about my son, Marky, to elucidate some finer points of treatment.

In the last six years of attending the "DAN" Conference annually, for the parents that have followed the "DAN" protocol faithfully, in almost its entirety, their children have made great gains. It has been reported that a fifteen- year old non-verbal male started speaking after correcting some of the biochemical abnormalities. Another eighteen- year old young lady started speaking for the first time after her biochemical abnormalities were regulated. There is now a protocol that is so effective that it is claiming 85 percent improvement! When you balance your child biochemically, all the other therapies work so much more easily, whether it's Applied Behavior Analysis (A.B.A.), Occupational Therapy (O.T.), Speech Therapy, etc. The child is happier, calmer and more focused. Very often, the child starts to retain what he is taught. One child even lost his "stim" behaviors after chelation. Wouldn't that be a dream? There is now some evidence that the gains made from ABA are not sustained as the years go by. It is believed that if the biochemical problems are not corrected, the toxins will eventually take away the gains one makes with the other therapies in many cases. There are no promises, but if you don't try, you'll never know how far your child can go!

In both Chinese medicine and Ayurvedic medicine, the sages believed that there were only two ways to health: one was to correct deficiencies; the other was to get rid of toxicities.

In Autism, the toxicities often are:

1. Mercury (and other heavy metals). Most Autistic children, genetically, cannot detoxify well. So when these heavy metals accumulate from vaccines in the form of Thimersol, (a preservative), in dental amalgams, in utero, from the mother's blood, seafood, water, etc., these children run into more trouble. Mercury toxicity creates a clinical picture very similar to Autism, even in adults.

Mercury binds to sulfur in cysteine, an amino acid present in many enzymes. There is solid evidence that one of these enzymes shuttles the innocent immune stem cells into the pathway Th1. In the absence of this enzyme, these cells get shuttled into the pathway Th2. The pathway Th1 converts the immune cells to fight viruses and yeasts. The pathway Th2 converts the immune cells to cause food allergies, asthma, eczema, and autoimmune diseases. Which pathway do you prefer? That is why, in Autistic kids, many have food intolerances and high yeast overgrowth. It might also be why many people believe that the predisposed infant cannot fight the measles virus in the MMR vaccine and ends up with Autism, days, weeks or months after the MMR vaccine (www.909shot.com) Evaluation and chelation (removal) of mercury and other heavy metals is a must. If the child has mercury dental amalgams, they must be removed ASAP!

An important finding is that about 85 percent of Autistic kids are high in Copper and low in Zinc. Furthermore, these kids are very low in an important protein call Metallothionein, or MT Protein. This MT Protein acts as a magnet to Mercury and protects the Autistic individual from further harm caused by mercury, among other important functions. This protocol claims that even older Autistic individuals can be helped, that great gains could still occur. Very often, parents of older Autistic children despair because it seems that there is nothing that can help these children. It seems that this particular protocol can help! Still, generally, the younger the child, the faster and more the improvements are. Also, the sooner that the casein and gluten free diets are started, the faster the progress is.

2. Food intolerances - because of toxins, maldigestion and abnormal gut flora, Autistic children develop the "leaky-gut" syndrome. Chains of amino acids (peptides) that are not supposed to leak through the bowel membranes into the bloodstream, do. This, in turn, sensitizes the body to these foods. Also, these peptides mimic eurotransmitters, so that they bind up the normal neurotransmitter receptor sites, affecting the development and function of the brain, adversely (This problem is metabolic and not just immunologic). The most common allergens and peptide sources are: casein (all dairy products), gluten (in wheat, barley, rye, oats), soy, and corn. Please note that eating one crouton is as bad as eating a whole loaf of bread. It has to be 99-100% avoidance. There are many hidden sources of gluten and casein. For instance, it is reported that McDonald's French fries are coated with gluten to keep the fries from clumping together, and yet this gluten does not show up in their product list.

A good resource is the Feingold diet. Also check on the websites that are in this synopsis. Again, just because your child does not go berserk after casein or gluten, it does not mean that they are O.K. with these substances; there is the problem of delayed hypersensitivities that symptoms do not show up until days later. Also, the byproducts of casein and gluten are toxic to the brain and will prevent your child from recovering as far as he or she should. Many DAN Doctors would not even enter a treatment agreement with you unless you agree to be serious about this diet! I know how hard this diet is; remember that I have a child on this horrible diet, too!

3. Yeast - because of the reasons mentioned previously, overgrowth of yeast happens in the majority of these kids. The byproducts of yeast overgrowth are toxic to the Autistic child. One must control yeast by diet (there are many books on yeast-free diets), anti-yeast medications (Diflucan, Nystatin, etc.) and pro-biotics (different strains of lactobacilli - some are tougher than others; some do not survive in the hostile environment of the gut). Remember that a normal IgG or IgM antibody test against Candida is not indicative of having no problems with yeast. The IgA test is the important one to see if there is yeast in the gut. There are excellent books on yeast-free diets. Most importantly, avoid sugar-laden foods!

In Autism, many children are picky eaters. Even if they are not, they often lack necessary enzymes and liver function to digest and absorb properly.

THE DEFICIENCIES FALL UNDER:

Vitamins

Essential fatty acids

Amino acids

Minerals

Enzymes and co-enzymes

I will include a list of supplements that Marky is taking. There are many protocols, with many rationales. When we write down the dosages, please take into consideration that Marky is 11 years old and weighs 75 pounds. Please adjust your dosages according to your child's weight. We include brand names with the supplements, just to be helpful, but there are many good companies, with many excellent products out there. If you are obtaining your supplements from other sources, make sure that they are casein and gluten free. If possible, they should be soy, corn and dye free as well. Different children will have different needs. Once you have the tests results, you will have to experiment with what works with your child. This list of supplements works well for many Autistic children. The most important fact to remember is that different Autistic kids responds to different treatments, our job is finding the treatment that makes a big difference!

TESTS NECESSARY TO DETERMINE TOXICITIES AND DEFICIENCIES

1. Hair analysis: In Marky this test indicated high lead levels. The absence of mercury, in this test, does not indicate that your child's mercury level is normal. If you cannot detoxify Mercury, it will not show up excreted in your hair. Watch for elevated antimony, which can also be a problem for Autistics. Lead often shows up high in this test.

2. Elemental analysis: packed erythrocytes In Marky, this test showed high mercury, copper and antimony. This test would show mineral deficiencies, as well as high levels of metals.

3. 24-hour urine elemental analysis: If this test is negative, it does not mean that the mercury is not high. In many cases, one would have to use a chelating agent to do a challenge test. In the challenge test, the chelating agent moves the mercury from the intracellular space into the extracellular space, so that it can be measured. If your child is not toilet-trained, you might want to do a 6-hour or 12-hour urine test, instead.

4. Plasma amino acids: Marky was deficient in 13 out of the 23 amino acids tested). These kids cannot digest well because of poor pancreatic and/or liver, biliary function. Often amino acid supplementation helps mental function. Many key enzymes cannot be produced in amino acid deficiencies. The 24-hour urinary amino acid works better than the plasma amino acid if your child is toilet-trained.

5. C.D.S.A. (Comprehensive digestive stool analysis): Marky showed very poor ability to absorb fat, hence, he was very deficient in vitamins A, D, E and beta-carotene. Marky's lactobacillus level in the bowels, was zero, even though we were giving him 60 billion a day. This test indicates what is happening to digestion and absorption. It would tell you how to repair the bowel condition and what is needed to help digestion.

6. Anti-Candida Antibody Test - IgA, IgG, IgM: Initially, these were very high in Marky, but after three years of antifungal treatment, they are now normal. You need to monitor the yeast level every two or three years after treatment, as recurrence often happens, especially when you are chelating.

7. Food allergy test - IgE, IgG: In food allergies, the IgE mediated response is obvious - you get an immediate reaction like hives, itchy eyes or difficulty with breathing. With the IgG mediated response, it's a delayed reaction, so that you may not even get the stuffy nose or headache until three days later. Please note that food allergens change, so that it is a good idea to repeat this test every year or two. The food allergens act as toxins and would interfere with your child's mental functioning, etc. For instance, one child became toilet-trained, two weeks after the allergens were removed. (ImmunoLab does a good job on this test).

8. CBC and Differential, CHEM 25: This is just to make sure that the blood count is normal and that the liver and kidneys are working well enough to chelate, if necessary.

9. Serum ceruloplasmin and copper that need to be tested in acid etched test-tubes and plasma Zinc done in EDTA test-tubes- this is done before and after Zinc loading before the actual Metallothionein Promotion takes place.

All these tests are available through Great Smokies Lab, 1-800-522-4762, (except the anti-Candida antibody - that is from ImmunoSciences Lab). Test # 8 can be done in any lab at all. Your doctor can also consult a Great Smokies staff doctor to go over all the results and recommendations, once the results are back. Dr. Pangborn is one of the world's geniuses in Biochemistry; he consults for Great Smokies.

The other labs that are also excellent for these tests are:

Biocentre Lab........1-800-494-7785

ImmunoLab.......1-800-231-9197

Immunosciences.......1-800-950-4686

Meridian Valley Lab.......1-253-859-8700

Metametrix........1-800-221-4640

Dr.'s Data Lab.......1-800-323-2784

Please note that only your doctor can order test kits from these labs.

USEFUL RESOURCES:

1. Dr. Sidney Baker's Book, "Detoxification and Healing" ISBN 0-87983-709-8 Publisher: Keats Publishing Inc. This book is easy to read and is very important to understanding Autism, or how to stay healthy yourself. In addition, Dr. Baker's web site is a very valuable source of information on Autism and healing. www.sbakermd.com

2. DAN Protocol: $25.00 Explanation of all of this material, more accurately and more scientifically. Phone: 619-281-7165 (Autism Research Institute). www.autism.com/ari

3. "Children with Starving Brains", by Jacquelyn McCandless M.D. A book that every Autistic child's parent should read and study ISBN 1-883647-09-6. It is a well-written book on the DAN protocol.

4. Another very informative web site is www.rxforautism.com

5. Web sites for casein and gluten free diets are: www.gfcfdiet.com www.gfcfkids.com and www.missroben.com

6. Dr. Megson at the Pediatric and Adolescent Ability Center www.megson.com

7. Valuable information on mercury can be found on the following sites: http://altcorp.com/autism.htm : http://www.house.gov/reform/hearings/healthcare/00.07.18/index.htm : http://www.cureautismnow.org/sciwatch/invest.cfm.

SUPPLEMENTS:

1. Transfer Factor: This is the first substance that we gave Marky that made a substantial difference in having him become more sociable, co-operative, calm, having great eye-contact and more speech. Transfer factor is extracted from colostrum or blood. It can be given by injection or orally. Transfer factor may have anti-viral properties, so that if you have the flu, and you take 9 capsules a day for three days, you may shorten the natural course of the flu. Initially, we did not believe that the MMR vaccine contributed to Marky's Autism, because Marky's Autism did not manifest until he was two years old. But if there were no viral inflammation, the transfer factor would not have worked. We noticed a difference in Marky in less than a week. Transfer factor also improves the environment in the gut.

There are two commercial sources of oral Transfer Factor that we are aware of:

a) Chisolm's Lab (Phone: 1-800-664-1333) This is a specific Transfer Factor against childhood flus, viruses, including MMR, DPT. At the present time, I recommend immune factor #4; they are supposed to be coming out with one specific to Autism soon.
Dosage: 1 cap/day. Dr. Bradstreet (www.gnd.org) had good results with this.

b)Life (Phone: 1-888-454-3374) This is a non-specific Transfer Factor. You start with 1 capsule 2x 1 day, then 3x 1 day, up to 3 capsules 3x/day. Dr. Peter Bock had the kids maintain this dosage for 3 months, then backed off to 1 capsule, 3x/day for maintenance.

2. DANplex (Phone: 1-800-792-6670). This is a vitamin/mineral/amino acid nutritional supplement, compounded by Hopewell Pharmacy, under the recommendations of many of the DAN doctors. Some people prefer Super-NU- Thera from Kirkman's 1-800-245-8282. There is also a good tasting multi-nutrient-Brain Child from Michael Lange, 1-831-465-9405.

3.Omega Brite (Phone: 1-800-383-2030). This is the best source of omega-3 and omega-6 essential fatty acids ("essential" means that the body cannot produce it from something else). These fatty acids are necessary for the maintenance of the cell membranes as well as cell-to-cell communication. Dr. Andrew Stoll has found that a dosage of 1 capsule, 3x/day, helped many Autistic children. When you are on this product, you don't need to continue with flaxseed oil or evening primrose oil.

4. Sphingolin (Ecological Formulas 1-800-888-4585). Many Autistic children have anti-myelin antibodies. You can do a specific blood test for this or just give a trial of this supplement. It is inexpensive and has no side effects that we know of, at the proper dosage. The dose is a half a capsule a day, regardless of the child's size. Please note that you should not be on Sphingolin and Secretin at the same time.

5. Cod Liver Oil (Kirkman Labs 1-800-245-8282). Dr. Megson (www.megson.com) has done remarkable research on the necessity of obtaining vitamin A (the "cis" form) from cod liver oil. It turns out that most of the vitamin A (including vitamin A from beta-carotene), is in the "trans" form, a form that we cannot utilize. The "cis" and "trans" forms are mirror images of each other; the "cis" form works better on the human body. The dosage is 1 capsule 3x/day.

There is also a good tasting, orange-flavored one called Dale Alexander's Cod Liver Oil, by Twinlabs, in many health food stores.

6. Digestive Enzymes: These help to break down the foods that the kids eat, into absorbable components. Most of the kids have very poor digestion. I recommend taking EnZym-Aid (Kirkman's), with another enzyme, which contains lipase, (such as b, c or d below), to break down the fats since EnZym-Aid has no lipase in it.

a)EnZym-Aid (Kirkman's). Phone: 1-800-245-8282

b)Plantizyme (Thorne's). Phone: 1-800-228-1966

c)Megazyme (Whole Foods). Creon - 10. Creon - 20 by prescription

7. Probiotics: This is to supply the body with "good" bacteria to keep down the yeast growth and to acquire many other health benefits from them. This is well explained in Dr. Sidney Baker's book. Remember, some lactobacilli do not survive the hostile environment of the unfriendly pH's in these children's intestines.

a)Lactobacillus sporogenes (Thorne) 1-800-228-1966 - This is a tougher form of lactobacillus since it is in the spore form.

b)Enterogenic concentrate (Preventhium)

Phone: 1-800-755-1327 (They often have phone problems)

Fax: 1-770-831-8610

c)Pro-Bio Gold (Kirkman's)

Phone: 1-800-245-8282

d)Cuturelle has the reputation that it can actually colonize in the gut. Many health food stores carry it.

8. Mineral Supplements

a)Citramin I or II (Thorne). Phone: 1-800-228-1966

b)Trace minerals (Thorne). Mineral supplementation is a must in chelation on the "off" days. Phone: 1-800-228-1966. It is also a good idea to add extra Zinc, as this mineral seems to be deficient in most Autistic kids. Zinc must be taken on an empty stomach, at bedtime, for best absorption.

9. D.M.G. (Kirkman's). This helped 40% of the Autistic kids in Dr. Rimland's study. You may need higher doses than you think in order to have a great effect. DMG helped Marky calm down, almost over-night after his car accident. He was pinching and biting himself and others to the extent of drawing blood. Now he is on 12 capsules a day. Phone: 1-800-245-8282

10. Fibre: Arabinex or Medibulk (Thorne) 1-800-228-1966. This is important for the health of the intestines as well as the survival of the lactobacilli.

11. Secretin This substance is helping a lot of Autistic kids, but not as many as originally thought. It is available in I.V., oral and skin patch forms. Again there is controversy as to whether the latter two forms work.

12. I.V. Glutathione: There have been some benefits with this therapy as far as calmness and getting rid of "tics" are concerned, as well as some acceleration in cognitive abilities. Of course, Glutathione is also available in oral and topical forms.

13. Metallothionein Promotion Therapy: This seems like a really exciting therapy with promising results as mentioned earlier in this synopsis. There is basically 2 phases to this protocol. The first phase is to increase the zinc and to decrease the copper. The second phase is to give the body the amino acids necessary to build the MT Protein. The MT Protein will then help the body heal and catch up in the necessary areas. Taurine interferes with Zinc absorption, so no Taurine on the days of Zinc Therapy.

14. A very exciting area is being researched at Harvard Mass. General Hospital where hundreds of Autistic kids are being endoscoped by Dr. Tim Buie. The findings are, that even in the absence of G.I. symptoms, there is inflammation of the gut. When the gut is given the appropriate therapies to heal, the Autistic symptoms greatly recede.

If you live outside the US, you might need to find the non toll-free number through a friend. In some cases, your friend might have to order it and ship it to you, as regulations may not permit shipping outside the country. This applies to all the toll free numbers mentioned.

Please remember that, if you introduce your child to a new supplement, it is not unusual for the child to experience some adverse effects for a short while. These effects may include hyperactivity, skin rashes and behavioral regressions. When this happens, it does not necessarily mean that you should discontinue the supplement, unless the adverse effects are dangerous, or persistent. Usually these side effects wear off in a few days. Please remember to start with a very low dose, even as low as a quarter capsule. If there are adverse effects, stay at this dose until the adverse effects are gone, then proceed to a slightly higher dose, etc. Marky became hyperactive for a few days, when we first started most of these supplements. In addition, you may not see the beneficial effects of these supplements for a period of time. Also remember that just because a therapy did not work before, it does not mean that you should not re-visit that therapy at a later time, for instance, after you clean up the gut problem. Please consult your doctor about any adverse effects that persist or cause concern.

GENERAL POINTERS TO CHELATION

1. Make sure your child is balanced nutritionally - i.e. amino acids, vitamins, minerals etc., before chelation. If the child is very out of balance, chelation may lead to seizures (especially if the child is low in magnesium or taurine)

2. Do not take mineral supplements on the days of chelation, but make sure you do take them on "off" days. Even though the agents are not supposed to affect calcium and magnesium, I found that taking extra amounts of these reduces the muscle twitching and headaches. The revision in the chelation protocol advises us to take some Zinc and some selenium even on the days of chelation. We find that doing this helps cut down the irritability by quite a bit. Also, Kirkman (1-800-245-8282) now has packages of replacements and supplements to support chelation.

3. In dosing of the DMSA or DMPS, chelating agents, remember to remind your doctor, to "go low" and to "go slow"!

4. Make sure you have a knowledgeable doctor supervising the chelation - what blood parameters to monitor etc. Dr. Rimland's institute, Autism Research Institute, has a list of doctors who are familiar with the DAN protocol. Phone: (1-619-281-7165). Again, we are set up to treat Autistic individuals anywhere in the U.S.A. or in Canada, so you can contact us at the e-mail or phone number at the beginning of this document, if you wish. We are passionate about giving our Autistic children their best chance!

5. There are three agents for chelation of mercury:

a) DMPS (Heyl is the purest brand) oral, I.V. or I.M.

b) DMSA (Chemet, Succimer). (Kirkman makes a very palatable form) oral.

c) DMSA with ALA (alpha lipoic acid) oral.

Allithiamine- this is a mild chelator and is used as a cream on the soles of the feet. The advantage of this treatment is that you don't end up with so many problems with over-growth of yeast and different bacteria as you do with DMSA or DMPS.

There are many chelation protocols, please consult either the web site of the Autism Research Institute www.autism.com/ari. Most chelation is done orally; some doctors implement the oral chelation with I.M. shots of DMPS.

Please note that most of the information from this DAN Conference (including the Autistic child's underlying inability to detoxify, deficiency states and toxicity and the treatments as discussed), is not yet widely accepted by the medical profession. The conventional medical community takes a very long time to embrace and accept new ideas. Don't be surprised if your doctor regards this information with skepticism (as I once did). You may need to find a DAN Doctor (see # 4 above) or a doctor who is open-minded enough to supervise the testing and treatment with you.

SUMMARY

In the beginning of this journey, I did not believe all the theories and explanations, presented at the DAN conference, even although I greatly respected the presenting doctors and scientists. How can so many things be going wrong, biochemically, in our Autistic kids? Throughout the years, we would try this therapy and then that therapy, with very minimal results. When we finally did all the testing recommended, we were shocked! All the things that they postulated at the DAN conference, turned out to be true for our son. Marky could not detoxify. He had high levels of mercury, lead, copper and antimony. Marky could not digest or absorb fat and was deficient in fat-soluble vitamins. Marky was also deficient in 13 out of the 23 amino acids tested. Marky also had yeast overgrowth, as indicated by his anti-Candida antibody test. He was allergic to 21 food items!

In a nutshell, we are trying to correct Marky's deficiencies, by giving him the supplements mentioned, as well as his amino acid supplements. We are trying to eliminate his toxicities by anti fungal therapies, probiotics, a diet free from his identified food allergens, and soon, by chelating the heavy metals. We are continuing Special Education Classes for three hours a day, individual tutoring for 6 hours a day, his Occupational and Speech therapies. It's really quite a lot, but then, the rewards are worth it! Marky is calm, happy, focused and interactive. Both his teacher and tutor state that he is learning faster and retaining what he learns. Also, both his expressive and receptive language has progressed markedly. We still have a long way to go, but hopefully, the chelation will give us additional improvement.

The DAN doctors and scientists now believe that Autism is a biochemical disease that can be helped greatly through much effort and persistence. I used to think that organic foods were for the truly neurotic. Now I believe that, for ultra-sensitive people, like our Autistic kids, organic foods are a necessity. Who knew that they could be, not only sensitive to so many foods, but also to dyes, preservatives, molds and fungi? In many cases, filtered water is also a must. So, be curious and be persistent. Take good care of yourselves so that you can endure this arduous journey called "Autism"!

Remember, the lesson is in the journey, not in the destination.

"Spiro, Spera" "While I breathe, I hope" Never give up!

God bless you and good luck!

ADDENDUM

1. There is significant evidence that the measles virus, in the form of the vaccination, MMR, plays an important role, in the etiology of Autism.

2. There are other more "in depth" tests as well, among them are:

Intestinal permeability

Detoxification profile

Vitamin profile

Essential fatty acids profile

All the tests for different antibodies, and immunoglobulins

3. This Metallothionein Promotion Therapy is claiming excellent results and bears watching and trying. We certainly intend for all our patients to be on it, after evaluation.

4. When the test results for the plasma or urinary amino acids are back, and you know what amino acids are necessary, a good compounding pharmacist is College Pharmacy (Colorado), Phone: 1-800-888-9358.

5. Prayer is very important! (Probably the most important)! "My Father, if it be possible, let this cup pass from me..." In our prayers, we alternate between praising God and groveling to Him!

6. If you find something that works for you, don't be afraid to pass it on to us, and to others; we would be very grateful.

7. Don't be afraid to do some of the tests or take some of the tests yourself. Remember that there is a genetic component to Autism so that the defects might be present, but to a slighter degree, in other members of the family. Also, don't forget that Autism is just a part of a spectrum that includes A.D.D., A.D.H.D., obsessive-compulsive disorder, manic- depressive disorder etc. Many members of the family feel and perform so much better on the diets and some of the supplements that these kids are on. You might want to have your mercury dental amalgams replaced. There is a Dental Materials Compatibility Test by Clifford Labs, (1-719-550-000), to find out which amalgams will not be toxic to you, in the long run.

8. Please feel free to photocopy this and distribute this to anyone who might benefit from it. You might want to send copies of this to your local and national parent support groups for Autism. Think big! We want as many children to benefit from this information, as possible. Maybe you might want to mail this out to other countries and ask your contacts there to forward this document to the local and national parent support groups there. This goes for all useful information that you might have. Let's not fight Autism alone, but as a united group!

Again, God bless you and good luck!

Miriam Jang, MD

Taking It to Vaccine Court

Rising rates of autism in California (long curve) and in U.K. (short curve). Start of MMR vaccination shown by arrows (CA, 1978; U.K., 1988).

Parents say mercury in shots caused their children's autism, and they want drug firms to pay. The industry calls its defense rock-solid.

By Myron Levin

Times Staff Writer

August 7, 2004

As parents of two severely autistic boys, Kevin and Cheryl Dass of Kansas City , Mo. , face a world of heartache and worry.

Last year Kevin, a FedEx driver, and Cheryl, a part-time hairdresser, spent $27,000 on therapy for their sons. Financially exhausted, they are gnawed by these questions:

How will they continue the special help that Dillon and Kyle, their 4 1/2 -year-old twins, so desperately need? Willthe boys — who barely speak, are not toilet-trained and go bonkers when taken out in public — ever be able to live on their own? If not, what will become of them when Kevin and Cheryl are gone?

"It's torn our life apart, it really has," Kevin Dass says. And, he insists, it didn't have to happen. The boys were born prematurely and alarmingly small. Yet at 3½ months, Dass says, they were given four shots in a single day, including three containing small amounts of mercury, a neurotoxin.

"They were still in the hospital on oxygen, staying alive, and they put this poison in them," Dass says. "They were fried. They were totally fried."

Like many anguished parents of autistic kids, the Dasses blame the condition on thimerosal, a mercury-based preservative that until recently was added to many routine children's shots.

Thimerosal was used to keep bacteria out of vaccines sold in multi-dose vials. But there were no studies beforehand of its possible effects on the developing brains of infants. And health officials, who aggressively expanded immunizations during the 1990s, did not consider that mercury exposure for millions of children would exceed federal guidelines.

Now, in a dispute overflowing with bitterness and rancor, more than 4,200 families, including the Dasses, are demanding compensation to help pay for their kids' special needs. Their claims have inundated an obscure branch of the U.S. Court of Federal Claims in Washington , sometimes called the "vaccine court."

The parents are pushing a disturbing theory: that their children were casualties of the war on disease, suffering brain damage from thimerosal by itself or in combination with measles virus in the measles-mumps-rubella vaccine. They blame mercury from vaccines and other sources for an epidemic rise in autism and related neurological disorders.

They theorize that their children were devastated because they were less able than most kids to clear mercury from their bodies.

Vaccine makers and health officials strenuously dispute the claims. While voicing compassion for the children and their families, they say there is no proof that tiny exposures — typically 1 part mercury per 10,000 parts of vaccine — can cause brain damage.

"There's simply no reliable scientific evidence" that thimerosal causes autism, said Loren Cooper, assistant general counsel for GlaxoSmithKline, the global pharmaceutical giant.

Dr. Stephen Cochi, head of the national immunization program at the U.S. Centers for Disease Control and Prevention, argues that only "junk scientists and charlatans" support the thimerosal-autism link.

In May, a committee of the national Institute of Medicine declared that evidence "favors rejection" of the thimerosal-autism link. Opposing studies, the panel said, were riddled with "serious methodological flaws."

In response, parent activists point out that some studies have indicated a link. They also charge that data were manipulated in one key study cited by the Institute of Medicine, and that authors of other studies had ties to vaccine makers.

At stake are not only vast sums of money but reputations and careers. Vaccine makers face a potential litigation nightmare. And the allegations confront two agencies: the Food and Drug Administration, which licenses vaccines, and the CDC, which is in charge of seeing that children are immunized against everything from polio to whooping cough.

The immunization program has been hailed as a spectacular success, responsible for saving countless children from illness and death. But if the parents are right, thousands of their children have become collateral damage.

For now, the main battleground is a tiny tribunal most people have never heard of.

The vaccine court was created in 1986 as Congress' response to a liability crisis. In rare cases, vaccines were being blamed for catastrophic injuries and even death. Makers were threatening to quit the business, which in turn threatened the vaccine supply.

The National Vaccine Injury Compensation Act shielded the industry from civil litigation by instituting a system of no-fault compensation. Under the law, aggrieved families file petitions, which are heard by special masters in the vaccine court. Successful claims are paid from a trust fund fed by a 75-cent surcharge per vaccine dose. The Department of Health and Human Services oversees the fund, with the Justice Department acting as its lawyer.

The autism case is approaching a crucial stage: a hearing within the next few months in which experts will joust over whether mercury causes autism.

If the verdict is no, the case ends there. If the special master finds for the parents, individual claims will be heard. A flood of successful claims could exhaust the $2-billion fund.

Big vaccine makers such as Merck, Wyeth and Aventis-Pasteur, along with Glaxo, are watching with trepidation. Though safe from liability in the vaccine court, they are anxious because claims have begun to leak into the civil courts.

Under the law, petitioners who have gone more than 240 days without a ruling in the vaccine court can opt out and file a civil suit. More than three dozen families who've waited long enough have opted out, and more are sure to follow. A handful of suits are set for trials next year in Texas , Pennsylvania , Maryland and Georgia .

A legal Catch-22 could doom many claims in both the vaccine court and civil courts. The compensation law requires that petitions be filed within three years of the first sign of injury. In many cases, by the time children were diagnosed with autism and parents learned of their mercury exposure, the deadline had passed. This technicality could cause as many as 60% of the petitions to be discarded in the vaccine court, lawyers for the parents say. And some civil courts have decreed that people who did not file on time in the vaccine court can't pursue civil litigation.

"The parents are going through hell. The children are going through hell," said Richard Saville, a lawyer for some of the parents. "What we're trying to avoid - is a situation in which no court ever hears their complaint."

Even so, families who reach the civil courts may gain some advantages there. They will have access to internal industry documents that are not available in the vaccine court. Moreover, whereas the vaccine court pays medical and living costs and up to $250,000 for pain and suffering, civil juries can award punitive damages as well.

Vaccine makers insist that their defense is rock-solid.

The evidence "is so overwhelmingly one-sided that we are confident that juries will overcome their natural sympathy for plaintiffs and decide these cases as science dictates," said Daniel J. Thomasch, lead outside counsel for Wyeth.

Privately, however, some industry figures conceded that when it comes to sick children and brokenhearted parents, science doesn't always win the day.

The companies "are terrified" of huge jury awards because "the injuries are so grave," said Kevin Conway, a lawyer for parents. "It's not just the kids, it's the parents, it's the siblings. These people just live emotionally exhausted and financially devastated lives."

Even if the companies are exonerated, victory will not come cheap. An industry representative, who predicted vaccine makers will win every case, said it could cost them hundreds of millions of dollars to do so.

Autism is the most severe of a range of neurological conditions called autism spectrum disorders. It limits the ability to communicate, form relationships and respond appropriately to the environment. Symptoms can include loss of language and eye contact, extreme withdrawal, violent or repetitive behavior, and extreme sensitivity to light and sound.

One in every 166 U.S. children suffers from an autism spectrum disorder, according to an estimate by the CDC and American Academy of Pediatrics. In California , the number of cases rose 273% from 1987 to 1998, according to the state Department of Developmental Services.

It's been suggested that broader definitions and better reporting are behind the apparent spike. But a study in 2002 by the MIND Institute at UC Davis found that these are at most minor factors, and that the increase is real.

In the search for a cause, thimerosal only recently became a suspect.

The compound is 49.6% ethyl mercury, not the methyl mercury found in fish and power plant emissions. Both forms are toxic, though some research suggests ethyl mercury is more quickly purged from the body.

Developed 75 years ago by Eli Lilly & Co., thimerosal has been used in vaccines since the 1930s and was the main ingredient in Merthiolate, an antiseptic daubed on millions of skinned knees before it was taken off the market 20 years ago.

Medical literature includes reports of thimerosal poisoning at a sufficient dose - along with advice to curb its use. Perhaps most alarming was a 1977 report on the thimerosal-linked deaths of 10 babies in Canada .

According to the article in Archives of Disease in Childhood, the antiseptic had been used to treat exomphalos, a type of umbilical hernia. Tissue and blood tests revealed high mercury levels in the dead infants. Moreover, the authors said, it "is extremely unlikely" that babies who survive the treatment "escape neurological damage, which may be subtle."

Mercurial antiseptics should be tightly restricted or banned from hospitals, they wrote, "as the fact that mercury readily penetrates intact membranes and is highly toxic seems to have been forgotten."

However, thimerosal remained the most popular of several preservatives used by vaccine makers to avoid the risk of bacteria from repeated needle insertions into multi-dose vials. Vaccines also come in single-dose vials or disposable syringes that do not require preservative. But doctors and clinics traditionally preferred multi-dose vials because they were cheaper and easier to store.

No one would have cared but for this confluence of trends: autism rates were rising, while more mercury was being injected into kids.

The CDC sets the country's immunization schedule, which, in effect, has the force of law, since in many places children can't enter day care or school or qualify for public assistance unless their shots are up to date.

Mercury exposure increased markedly in 1991, when the CDC added hepatitis B and Haemophilus influenza type b, or Hib, vaccines to the schedule.

Because these were mostly sold in multi-dose vials, children whose dutiful parents stayed current with their shots received as many as nine injections with as much as 187.5 micrograms of mercury in their first six months of life — exposures well above Environmental Protection Agency guidelines.

This was disclosed in 1999 in a federal review, which showed that health authorities had ignored the rising exposures as they added shots.

In e-mails to colleagues at the time, Dr. Peter Patriarca, a senior FDA official, acknowledged that the agencies were open to attack. The FDA could be charged with "being 'asleep at the switch' for decades by allowing a potentially hazardous compound to remain in many childhood vaccines, and not forcing manufacturers to exclude it from new products," he said in a June 29, 1999, e-mail later disclosed at a congressional hearing.

It didn't take "rocket science" to track the rising exposures, Patriarca wrote. Critics may wonder "what took the FDA so long to do the calculations? Why didn't CDC and the advisory bodies do these calculations when they rapidly expanded" childhood immunizations?

In July 1999, the CDC and American Academy of Pediatrics called on vaccine makers to remove thimerosal as a precaution. Manufacturers began switching to single-dose containers. By 2002, thimerosal was present only in trace amounts in routine vaccines.

Now it is making something of a comeback. This year, the CDC added flu shots to the vaccine schedule for children 6 months and older. Aventis, the only producer of flu vaccine for infants and toddlers, makes it both in single-dose and mercury-containing multi-dose vials. The CDC has spurned appeals to recommend thimerosal-free shots for all children and pregnant women — fearing parents might refuse a shot for their kids if they couldn't get it mercury-free.

Exasperated by the agency's stance, lawmakers have filed bills in Congress and several states, including California , to ban thimerosal from pediatric vaccines.

Cochi of the CDC says such bills are ill conceived. He says children die of the flu, including more than 140 last year, while the risks of thimerosal are at most theoretical. He blames the uproar on those eager "to capitalize on the tragedy of parents with children who have autism, because they see a huge pot of gold at the end of the rainbow."

"That's the other side of this story," Cochi said, "that it has the potential to be a gigantic scam on the American taxpayer."

Of all the resentments of the parents, the idea that they are out for a buck seems to gall them the most.

And when they talk about their lives — the social isolation, financial distress and bleak prospects of their children — many can't help but weep. At such times, it's easy to see why vaccine makers would rather not face them in court.

Kyle and Dillon Dass arrived three months early in January 2000 — weighing 1 pound, 7 ounces and 2 pounds, 15 ounces, respectively. That was six months after the appeal to remove thimerosal from vaccines.

Kevin, their father, keeps a copy of an advisory sent to doctors by the Academy of Pediatrics shortly before his sons were born. "If there are limited supplies of thimerosal-free products available, priority should be given to use in premature infants," it says.

At 3 1/2 months, the boys got four shots in one day. Three contained thimerosal, according to medical records the Dasses later obtained.

At the time, the couple had never heard of thimerosal, but Cheryl Dass said she questioned giving several shots to her tiny babies. She did not put up a fight, however, deciding, "Oh well, you know what you're doing because you save lives everyday."

Lyn Redwood, who lives near Atlanta , says her son Will began receiving doses while still in the womb.

Redwood, a former nurse, had amniocentesis during pregnancy. Because her blood was Rh negative, after the procedure she was given shots of gamma globulin to protect her fetus from an illness called Rh incompatibility disease.

Years later, Redwood said, she was amazed to learn that the two gamma globulin shots during pregnancy, and a third when she was breast-feeding, contained thimerosal.

Will, who has pervasive development disorder, a milder form of autism, had received an additional 237.5 micrograms of mercury in vaccines by the time he was 1 1/2 , Redwood said.

Even so, he seemed to progress nicely until his first birthday. Redwood recalled that he started to walk, talk and generally do things on time — before suddenly regressing and slipping away. "He stopped looking at us. He stopped playing…. It was like 'Invasion of the Body Snatchers,' " she said. "Somebody had taken away my baby's soul and just left a shell of him in there."

The bizarre and disruptive behavior of many autistic children can make their families virtual prisoners in their homes.

Going out in public "is a train wreck," said Cheryl Dass. It's impossible to do the family things others take for granted, like going to a movie or church or "even to pick out a pumpkin."

Kelly Kerns of Lenexa , Kan. , who has an autistic daughter and twin sons, said, "We're not the families that are doing baseball and birthday parties.

"I'm a mother that lives in a tunnel," she said. "I haven't been to a family reunion in four years. My family doesn't understand. They wouldn't understand.

"I used to be a decent person, and I just have acid rolling from my lips every time I open my mouth," Kerns said. "I ask God every day what did I do to deserve this. What did these kids do to deserve what they got?"

Some parents are hopeful, though not holding their breath, for help from the vaccine court. Others say they'd just as soon get a chance to bloody the industry in a civil trial.

Said Georgia Mueller of Kansas City , who has an autistic son: "I want it to hurt" the manufacturers, because they "never did the research to make sure this was safe."

Major CDC Study on Thimerosal Flawed

Author Admits Findings Incorrect

The author of a major study of the link between Vaccinations and Developmental Disorders which is widely quoted by the Centers for Disease Control and Prevention (CDC) has admitted that the study is inaccurate in its findings. Dr. Thomas Verstraeten, of the CDC's National Immunization Program, is quoted as saying, "One thing is for sure, there is certainly under-ascertainment of all these [conditions] because some of the children are just not old enough to be diagnosed." This was confirmed by a professor who has reviewed the research. He stated that there were too few children in the study to pick up all cases of autism.

The study in question has been widely quoted as evidence that Autism and other Pervasive Developmental Disorders are in no way linked to the vaccines which are routinely given to children around the world. Now it seems this conclusion is invalid and the true relationship has yet to be discovered.

Additionally, it appears that the CDC is now reversing its stand. According to the Sunday Times, the Centers for Disease Control and Prevention has found a "statistically significant" link between mercury in vaccines and developmental disorders, including Attention Deficit Disorder and speech and language delays. The CDC, however, still recommends vaccinations with thimerosal containing vaccines, saying there are safety measures in place to prevent overdoses of mercury.

Autism rates around the world are rising and the rise coincides with the availability of more vaccines containing mercury, a lowering of the age at which vaccines are given to babies and the introduction of the combined MMR vaccine, which does not contain mercury, but which has been linked to Autism by some researchers.

Now that the research quoted by the CDC and other governmental agencies has been found inadequate, and since there are research findings which suggest a link between mercury and developmental disorders, it is time to begin serious research into these issues. In addition, the link between the MMR vaccine and Autism should be explored further, since it appears to be associated in some way with the increased rates.

In spite of the dangers of mercury exposure in infants, the CDC continues to recommend that, "State and local immunization programs or private health care providers should use the vaccines available in their stock. All vaccines are safe and effective as stated by FDA." Yet the American Academy of Pediatrics and other medical groups has called for the removal of mercury from all vaccines. Why then does the CDC continue to state that they should be used? While they say they are working cooperatively with vaccine manufacturers to implement a plan to reduce and eventually eliminate future purchases of thimerosal containing vaccines for federal programs, it appears that these moves may be too little, too late. While the government is, "working cooperatively," with the manufacturers, more and more children are being exposed to potentially toxic levels of mercury and more and more families are having their lives destroyed by its effects. The time to act is now.

Congressman Dan Burton (R-Indiana) and others have called for the removal of all vaccines containing thimerosal. So far their words have fallen on deaf ears. Vaccines with excessive levels of mercury are still being routinely used and there is no clear end in sight. Until adequate research is done either proving or disproving the relationship between these vaccines and neurological damage, their use should be discontinued. Vaccines which do not contain thimerosal are available and their use should be mandated by the federal government.

A Testimony to Congress