Paul Shattock and his Autism Research Unit at the University of Sunderland have discovered that autism shares traits with Gulf War syndrome the result of catastrophic chemical overload

The usual medical view is that most autism is due to a genetic disorder, and with good reason. The existence of so many families where autism and related spectral disorders appear again and again is compelling evidence.

However, this is probably not the whole story. Even the strongest proponents of genetic research are now beginning to talk in terms of ‘genetic fragility’ or ‘genetic predisposition’.

Genetic susceptibility is not a black or white, yes or no, issue. Taking the population as a whole, the genetic susceptibility to any form of illness is more likely to be in the shape of a

normal distribution curve. A few people will be immensely susceptible, the vast majority will be moderately susceptible and some will be immune whatever the size of the burden.

Incidence skyrocketing

Increasing reported levels of autism have been noted from many parts of the world, but this may reflect no more than an increasing awareness of the disorder and changing diagnostic criteria (Br J Psychiatr, 1998; 158: 403-9; BMJ, 1996; 312: 327-8).

However, two recent reports on autism and vaccination would suggest otherwise. One paper, by Taylor et al, showed a whopping 1700 per cent increase of reported incidence between 1979 and 1992 (Lancet, 1999; 353: 2026-9).

Another 1999 study report showed a 273 per cent increase in autism for the state of California over a similar period. Studies from the past 12 months indicate a continuing rise in the reported incidence (Changes in the Population of Persons With Autism and Pervasive Developmental Disorders in California’s Developmental Services System: 1987 Through 1998, report to the State Legislature from the California Health and Human Services Agency, March 1, 1999).

Informal and unpublished data from many parts of the UK (Thrower D, Evidence presented to HM Government, 1999) and other parts of the world are showing similar increases. Although not supported by official publications, parallel, staggering increases in incidence apparently are occurring in similar and related disorders such as dyslexia and attention deficit disorder (ADD), which may be combined with hyperactivity (ADHD). Indeed, reports from the US and Australia suggest that 10 per cent of school age children are currently taking Ritalin to ameliorate the symptoms of ADHD.

In other circumstances, such increases would be regarded as an epidemic and worthy of concern and considerable research. So far, environmental factors have been completely and utterly ignored by government funded agencies within the UK and throughout the world. If these increases are indeed genuine, then there must be factors, additional to the purely genetic, which trigger the problem.

Although there may be genetic elements or ‘fragilities’ involved in all of these situations, the fact that the increases have been so dramatic point to environmental factors.

Environmental agents

Numerous environmental factors have changed over the past 20 years in the UK. The use of lead paint has decreased dramatically, as has the use of mercury in pesticides and dental fillings. Asbestos has been largely removed from the environment, but there are increasing levels of aluminium in water and potentially toxic fumes and radiation from TV sets and computers.

One of the biggest changes is an increase in the use of attenuated strains or non infective versions of many diseases, introduced in the form of vaccines. At the same time, levels of mercury injected into infants in the form of preservatives (thimerosal) increases every time another infection is added to the list of recommended or mandatory vaccine programmes.

The other big change involves the fact that the older organochlorine (OC) insecticides have been replaced by those based upon organophosphorus (OP) compounds.

This leads us to a consideration of infectious agents and environmental chemicals, and their effects on the immune system, in what we have termed the ‘opioid excess theory of autism’ (see box below).

MMR vaccination

Dr Andrew Wakefield, of the Royal Free Hospital in London, which specialises in bowel disease, published a study of 12 autistic children showing that all 12 had gross intestinal abnormalities, with 11 showing ileolymphoid nodular hyperplasia, patchy chronic inflammation of the colon and abnormal growth of small nodules of lymphoid tissue (Lancet, 1998; 351: 637-41). Two children had thrush like ulcers plus huge swellings in the small bowel. In all cases, the children had been developing normally when they suddenly lost their speech and other skills, and began exhibiting symptoms of autism. Eight of the 12 developed autistic symptoms within 14 days of receiving the MMR jab.

All the other heavily quoted contributions to this debate (Lancet, 1999; 353: 2026-9; Lancet, 1998; 351: 1327-8; Autism, 1998; 2: 423-4) have relied on the manipulation of epidemiological data or, as in the case of Fombonne (Lancet, 1998; 351: 955) and Afzal (Lancet, 1998; 351: 646-7), are not relevant to the situation.

In a review of our own records, we attempted to demonstrate that those children who according to their parents showed dramatic and rapid behavioural regression within a very short time of receiving the combined MMR vaccine formed a separate subgroup within the autistic spectrum. We were able to outline certain clinical characteristics which we believe could be useful in defining this group.

In addition, our evidence suggested that certain children, diagnosed with some form of autism, have urinary peptide profiles at least in the majority of these children that differ significantly from those obtained from people who have more typical forms of autism. Wakefield’s work suggests there are identifiable biological differences (see box, p 2).

OP pesticides

When urine samples are taken from children diagnosed with autism and related disorders, a majority up to 80 per cent show increased levels of indolyl acryloyl glycine (IAG) in the urine, an abnormal metabolite of the amino acid tryptophan that may be created under certain conditions during tryptophan metabolism (Amino Acids, 1999; 17: 401-3).

As yet, there’s no published evidence that IAG has any marked physiological activity (though this possibility is being investigated in our laboratory). But, given its molecular size and structure, it is likely that the only known precursor for IAG indolyl acrylic acid (IAcrA) possesses considerable potential for activity. In particular, it could become involved in the structure of cell membrane fats, greatly increasing their permeability to other molecules.

As far as autism is concerned, what particularly interests us is the effect of IAcrA on the permeability of the intestinal wall and the blood brain barrier. Increased permeability would permit the increased translocation of biologically active peptides from the intestines to the central nervous system.

In Hartnup disease and phenylketonuria (PKU), the cause of the increased levels of IAG in the urine is believed to be purely genetic, but there could be other reasons. Through our associated studies, we have found what appears to be elevated levels of IAG in certain other conditions, in particular, in those experiencing symptoms commonly known as ‘Gulf War syndrome’.

At this time, we are investigating the possibility that OP based pesticides may be at least partly responsible for these abnormally elevated levels. Certainly, the US and UK forces deployed in the Gulf would have been exposed to such compounds, as are those suffering from ‘sheep dip syndrome’ (‘fruit pickers syndrome’ in the US). All of these individuals experience marked psychological as well as physical effects.

OP compounds were developed as agents of war (‘nerve gases’) and insecticides because of their ability to cause paralysis by inhibiting certain enzyme systems and, in particular, those involving anticholinesterases, thereby affecting the central nervous system and muscle control. OP compounds tend to be non specific in their actions and may affect other enzyme systems as well.

Most interesting in terms of autism is the effect of OP compounds on the enzymes involved in tryptophan metabolism (Biochem Pharmacol, 1992; 44: 2243-50; Eur J Pharmacol, 1993; 248: 237-41). Diazinon, an OP pesticide, has been reported to seriously interfere with the metabolism of tryp tophan via the kynurenine pathways, an intermediate amino acid in tryptophan metabolism. This, in itself, could be sufficient to push tryptophan metabolism towards producing IAG. If there are also effects on the enzyme tryptophan hydroxylase (which we are currently investigating), then this may be an additional impetus towards creation of the abnormal metabolite IAG.

The Gulf War only lasted a few days, but it was by far the most toxic war in history. In addition to the pesticides (mainly OPs) used by the allies to protect their troops and any which may have been derived from other sources, both troops and civilians were exposed to toxic products from burning oil wells. Soldiers had the additional burden of up to 12 separate vaccinations, some containing the mercury based preservative thimerosal, all administered on the same day. There was also the very strong likelihood that depleted uranium which, in spite of its name, is still radioactive was absorbed. In effect, our soldiers were exposed to all the main forms of modern contamination in combination with an unusually stressful and threatening situation. It would be astonishing if these individuals, given such exposure, returned from the Gulf War with their health intact.

The symptoms of Gulf War syndrome are similar (but not identical) to those seen in myalgic encephalitis (chronic fatigue syndrome). As with autism, the appearance of the symptoms might be explained by the combined effects of environmental factors, such as pesticides, and infections, which may be natural or induced through vaccines on individuals of varying genetic fragility.

Another line of evidence which points to a similar cause between the two syndromes is the reported usefulness of dietary interventions, specifically, elimination of gluten and casein. This has been shown in several studies to ameliorate some of the symptoms of Gulf War syndrome and other forms of autism (Autism, 1999; 3: 45-69) and is supported by personal reports at our own institution.

If this is true, increasing levels of OP compounds in the environment would, through a sequence of stages, result in increasing permeability of membranes of the intestines and the blood brain barrier as well as other membranes, such as those lining the respiratory organs. The increased permeability of such membranes would permit the passage not only of peptides, but of slightly larger polypeptides or even protein material. These molecules could be large enough and present in sufficient quantities to cause antibodies to be produced which, in turn, generate allergies or hypersensitivities.

Thus, we could anticipate increased incidences of autism and its associated disorders as well as hay fever, hypersensitivities and afflictions of the intestinal tract. Bovine spongiform encephalopathy (BSE; Creutzfeldt Jakob disease) might be explained in this way.

It was soon after the switch from the older organochlorine to OPs (between 1979 and 1982) that these problems arose. BSE made its first appearance between 1984 and 1986, followed by ‘new variant’ CJD the human form a couple of years later. Interestingly, it is reported that the first victims of new variant CJD were farmers. Perhaps this was, as reported, because of their proximity to afflicted cattle, but it could also have been as a consequence of their intimate and frequent contact with OP pesticides. The damage from OPs would then have facilitated transmission of the disease.

There appears to be an increase in the incidence in autism and of many other disorders which, at first sight, are apparently unrelated. The increases are real and not merely the aftermath of improved diagnoses. If this is the case, environmental factors are certain to be involved. There are many possible factors, but two important common areas are the infectious products introduced by vaccination programmes and the wholesale use of OP insecticides.

But, with thousands of pesticides awash in the environment and dozens of vaccination jabs into the arms of infants, the genie is already out of the bottle. Only after an entire generation is exposed will we know for sure.

!APaul Shattock

Paul Shattock is head of the Autism Research Unit, University of Sunderland.

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