The Environmental Toxin Sampling Liability Theory of Autism

“NO ONE KNOWS WHAT CAUSES AUTISM” is repeated in scientific articles, in news reports by people who do not take the time to research for themselves what is actually known about autism.  In “Causes”, I introduce a description of a process that is seen in the full literature on environmental and genetic causes of autism.  However, I do not spend sufficient space in the book outlining it in full detail.  Here, I offer a more complete description that I hope will help those without science degree understand how autism comes about, the roles of genes and environmental toxins, and what we all can – and must do – to help kids with autism have better days, but also to shut down the epidemic of autism.

OUR INFANTS are exposed to environmental toxins before birth.  Every agricultural and industrial toxin in our air, water, and food that makes it into our bodies has the potential to disrupt key biological pathways that are critical for life.  Some of us are more sensitive to these toxins than others.  When that sensitivity is inherited, and has a genetic basis, the genes that confer that risk are called “Environmental Susceptibility Genes”.   Some chemicals, like estrogen mimics, disrupt hormonal patterning.  Others disrupt basic biochemical processes essential to life – like the cell’s ability to divide normally, or to rid itself of waste and toxins. Some toxins target specific cells, while others have a more widespread effect throughout the body.  Some disrupt or alter our immune system; others make it into the brain, and disrupt key processes like the need to get rid of excess glutamate, or the ability to create complex local neurological connections between nerve cells during learning.

We are all constantly bathed in toxins, from PCB’s, which accumulate in the environment, to organic solvents and chemical that reflect a highly industrialized way of life.  The cars with drive, the clothes we wear, the houses we live in all contain traces of solvents and adhesives used in the manufacturing process.  Cleaners in our home, and industrial solvents and pesticides in our garage all have the ability to cause damage to human tissues.

The greatest concern over these chemicals is the effects they can have on the developing brain. Pre-natal exposures are especially worrisome – but how does a pregnant mom escape the world in which she lives, works and sleeps?  A healthy brain development program is a complex process that occurs in a series of overlapping stages, beginning around week 6 of gestation, when neuron production in humans begins. The central nervous system lacks organization but the cells continue to divide along with the rest of the cells in the embryo for two weeks. During this week, cells in the embryo differentiate into neurectodermal stem cells, which will give rise to the brain and central nervous system. The neuroectodermal stem cells are the neural progenitor cells. The first brain structure to develop is the neural tube, which forms during the third week of gestation. Key nutrients and co-factors must be present for proper neural tube development, and a wide variety of chemical exposures at or leading up to this time can threaten the processs. The embryo, now just 3-5 mm long at the beginning of week 8, grows rapidly to 27-31 mm. During this week, the basic organization of the central nervous system begins to take shape.  Chemical exposures during this week can have profound effects on the viability of the embryo in general, and in the proper shape of neurological structural developments at this time.

This tiny person inside a mom is about to embark on an amazing journey of brain development and growth that requires very precise signaling for timing of further tissue differentiation, axon guidance, and the amount of cellular division leading to a recognizably mammalian brain structure.  However, the overall brain structures (gross morphology) is not typically distinct between autistics and neurotypicals.  Early difference in life may be noted by MRI studies, but these studies lack sufficient detail to examine synaptic architecture, the shape of the connections between brain cells, which is where the answers to the causes of autism resides.

The most important and significant event in the evolution of human was the development of an advanced, multi-layered neocortex.  It is here where the most advanced analysis, interpretation and synthesis occurs in the human brain.  The development of the neocortex really takes off from pre-natal week 11 and continues non-stop until well after birth – age 3.  The complexity of these processes, and the detail to which we know the actors involved (meaning protein signaling) is simply astounding to review. The result is a six-layered organization to the neocortex, with differentiation and regionalization into sensory, motor, and association areas – all incredibly important for proper human brain functioning.

There are key development programs that must take place for the regionalization and specialization of function to occur – but brain development does not take place in a vacuum.  The human brain receives input from the environment from the beginning of the first appearance of neurons (3-4 weeks).  Whether (if) and how the embryo is making “sense” of that input in a manner consistent with our understanding of “awareness” is hard to nail down, but the human fetal brain has regular measurable EEB activity by about 25 weeks (mid 3rd month gestation).  But sensory input is measurable per se in cell lines in petri dishes measured by transmission and reactivity to stimuli.  Moms, your baby was bathed in swishy sounds of your bodies, pressure, warmth, and your voice from the beginning, and could “sense” inputs from week 3, with experiences becoming more enriched by more complex brain structure developments with each passing day.

GENETIC MUTATIONS can alter brain development processes – of this there is no question. But there are a few facts about genes related to autism that are routinely overlooked by the media in the US.  First, there are over 850 genes that have been identified as being “associated” with autism.  However, no single gene accounts for more than 1% of autism liability.  Further, the largest genetic studies could only conclude that genetics “explains” (or is liable for) no more than 50% of autism.  The rest, they conclude, are “non-genetic factors” (aka, the environment).  That is a lot of liability for environmental factors.  However, the environmental liability is likely even higher, because these studies did not measure a single environmental exposure.  In genetic studies seeking to understand the relative importance of genes and environment, it is standard to describe it in terms of the amount of variation in the phenotype (the characteristics or traits of interest) as

Phenotype = Genes + Environment + (Genes x Environment), or

P = G + E + (G x E)

Here, G x E (pronounced ‘G by E’) represents the interaction between genes and the environmental influences.  This means the influence of the environment on the expression of genetic variation, of course. Because the largest genetic studies did not measure E, they could not estimate G x E.  Therefore, some (and I think most) of the importance G only makes sense in the context of E.

I Found Three Classes of Autism Genes

In my review of >2,000 studies on autism for “Causes”, I could recognize the function of many of the genes and the role they play in human phenotypes relevant to autism, brain functioning and behavior.  I recognized three major categories of ASD genes:

Autism Risk Genes

These are genes that are likely to cause problems with synaptic functioning, or neurotransmission.

Environmental Susceptibility Genes

These are genes which, if not functioning properly, are likely to confer increased risk of autism due to exposures to environmental factors.

Autism Phenotype Modifier Genes

These are genes that appear to contribute to an ASD diagnosis, but which, in reality, without the environmental exposure(s), merely contribute to variation in humans in terms of sociality, language ability, intellectual ability, and even tendency to perform repeated motions such as leg bouncing, pen tapping, finger tapping.  These repetitive motions are not considered pathological or medical (but may be considered impolite) in neurotypicals, but these traits may be exacerbated in persons who have an aberrant excitatory/inhibitory nerve transmission ratio due either to (other) genetics, or due to the effect of environmental toxins.

Microglial Excitotoxicity Points to Environment – or To Mutations

When mercury and aluminum enter the brain, they damage astrocytes.  One of the jobs of these cells is to uptake and recycle glutamate, an excitatory amino acid, and turn it into glutamine.  This is then fed back into a neuron for re-use as glutamate. When astrocytes can‘t work, an excess of glutamate occurs.  This causes other specialized cells called microglial cells to act as if there is a serious brain infection, or severe brain injury – and they stop performing their normal function, which is to help create complex nerve connections – and they go into attack mode.  They attack dendrites and neural precursor cells (see envgencauses.com for references).

By being absent from their duty to hand-hold dendrites and axons, and by inducing cell death in neurons (by destroying dendrites) and by over-pruning, microglial cells leave behind a brain much simplified, with many 1:1 connections, and few many:many connections.

These many 1:1 connections lead to strong signalling between distant part of the brain: there is not sufficient inhibitory feedback that normally occurs at complex synapses.  This explains why autistics are super-sensitive to their environment – light, sounds, pressure, etc. all come in through the senses, and because they can go deep and far into the brain, the senses can become overwhelming.  It seems likely also to explain why autistics sometimes have repetitive motions – their sensory inputs can make it all the way to the motor neural cortex, uninhibited, which responds by sending signals to the body to move.

Mutations in these key pathways can mimic, or exacerbate the effects of environmental toxins.

Why Mutations Cannot Possibly Be the (Only) Explanation

The first reason why is an epidemiologic one: the rates of autism have increased faster than a genetic condition can spread throughout the population.  However, 20% of autistics have increased copy number variations, and no one know why.

While deleterious mutations in glutamate receptors can add to the risk of autism, their effect would be to decrease the ability of the brain to clear glutamate, either from normal brain transmission, or from the occasional infection or small amount of cellular injury.  Autistics from age of 5-25 have high glutamate levels in the brain.  From ages 0-3, the human brain experiences a number of serious, and repeated environmental insults, either by accidental falls, or from vaccines. Encephalitis from vaccines is certainly a well-established fact.  But the repeated exposure to metals, known to partly take up long-term residence in the brain, is likely to lead to increased disability to clear glutamate.  Further, ethyl mercury specifically inhibits ERAP1 – the cellular protein responsible for shortening our immune system proteins (such as antibodies).  (This is likely why people who get the flu shot are more likely to develop other respiratory infections – their immune system becomes compromised by thimerosal.  Vaccines without thimerosal are available.

Repeated and accumulating doses of neurotoxins from vaccines that inhibit astroglial glutamate uptake are likely a predominant cause of autism.  Individuals that also happen to have rare mutations that break key synaptic proteins (rare because they are sub-lethal), or a mitochondrial mutation, or a mutation in genes related to serotonin processes then will likely experience more severe autism.

Environmental Toxin Sampling Liability Theory

The mutations that exist, scattered across the human population, that are “associated” with autism range from very rare to very common in the human population.  Absent the repeated environmental insults, or the diversity of environmental exposures, individuals carrying these mutations would likely not develop autism.

Under ETSL Theory, different families have different sensitivities to different specific toxins.  As they experience life, they are exposed to the same toxic soup as the rest of us – but, due to genetic variation, they are more susceptible to some specific toxins than others:

 

 

Figure 3. Large circles represent families w/distinct mutations conferring increased risk of autism due to specific environmental exposures.  Small circles represent the toxic soup we live in; each color a different toxin. These are not hypothetical; they are based on the literature reviewed in “Causes”.

These individual exposure types and specific genetic risks increases the likelihood of neurodevelopmental disorders in their children.  Their child may also have a de novo mutation that increase risk (not found in mom or dad).  These children are sitting ducks – already compromised by a specific G x E interaction (Figure 3), and by the ambient toxic load present in our environment, they then are subjected to (what to them) are intolerable doses of toxins in vaccines (Figure 4).  In particular, the large number of doses of aluminum now pushes these individuals over the edge, leading to full-blown diagnosis of autism.

Figure 4. When members of these families then experience the repeated high doses of aluminum from the current CDC vaccination schedule, it pushes them over the edge because the aluminum damages both their astrocytes, and, like mercury, their endoplasmic reticulum.  See envgencauses.com for references.

The Bad News

Due to our toxic environment, and in part due to genetics, vaccines as currently formulated are very dangerous for some families.

The Good News

We know why.

The good news is that with the proper experimental design (Phase Biomarker Research), the genetic information can be used to screen individuals who are likely at risk, and remove them from harm’s way.  Even insurance companies would like to avoid the additional high cost of medicine for autistics if the final insults could be avoided. Pediatrician’s practices could bill up front for biomarkers for screening (about $1,000 per clinical exome sequencing test, gross), and could save insurers $3,000-$4,000 additional per autistic child – per year.

The other good news is that via genetic biomarkers and protein biomarkers, combined with other indicators of familial risk. more kids will be able to talk, socialize, and relax.

Further, if the Vaccine Safety Biomarker paradigm takes off, there will be fewer seizures and other adverse events from vaccines, and, likely, less autoimmune disorders.  Specific risk per vaccine per condition is the goal.  We need to use what we know. Variation in the following genes increase risk of both seizures AND ASD following vaccines: IFI44L CD46 E3A gene UBE3A, TSC1 and TSC2 genes, SYN1, and DYRK1A.   We need to perform the studies to test their utility in reducing vaccine injury – and we need to have done this ten years ago.

Another positive is that the Vaccine injury compensation program could become obsolete – and the billions collected could be give the parents of kids w/autism, many of whom are now becoming adult.  Those who have been denied NEED these funds now.  They have paid an addition $17,000 per year per autistic child, on average.

If I were POTUS, I would ask Congress to create an ASD/ADHD/Autoimmunity pay out in the form of a tax break/tax rebate – with every family and individual receiving at least $306,000 paid out over the next 18 years – with inflation adjustment- to compensate them for bearing the cost of the US immunization program.  No, I’m not running for public office.  I’m just a scientist who never stopped doing science.

If the Vaccine compensation fund is dwindling due to the $3.5 billion paid out since 1986, the biomarker screening program could provide additional pay-ins to compensate those already injured.  Or Americans could be asked to tighten their belts and do what’s right and pay for these injuries the traditional way.

It’s time for the US to own up to the damage done to our own families out of fear of childhood diseases.  We need to move beyond mandates, which will bankrupt the system eventually with injuries, and move to make immunization safer for everyone who wants it.  For those who do not want any form of artificial immunization for themselves and their families, I can certainly see why, and respect your Right to Choice.  I have called for ban on NICU vaccination (250 mcg aluminum in a 3.3 kg body?!!?!), and agree with Dr. Paul Thomas that HepB vaccination at birth is superfluous.

There’s meme in the vaccine risk aware community called #knowtherisk.  Biomarker safety screens will inform pro-vaccine parents of the risk before the injury.  They could then be fully informed.  That is what everyone in the VRA community says they want.  Let parents and doctors #knowtherisk.  Biomarker science will require the scientific community to objectively measure that risk, and then give the medical community a tool to reduce the risk.

For those who believe vaccines injure everyone, I cannot disagree.  But I can’t yet agree.  We don’t know the effects of the CDC schedule on IQ, on crime rates, etc.  They have not been studied.  They need to be.  And, in the meantime, as vaccine risk awareness grows, parents will become increasingly empowered to exercise their freedom of choice.  There are those who are concerned that biomarkers would lead to mandates for the rest.  I can’t see it.  The medical community would be confronted with objective measures of injuries at the population-level as a result of the biomarker studies.  Then they, too, will truly #knowtherisk. And if safer means of immunization can be developed as a result, the current unhappy dark ages of the medieval practice of injecting toxic metals into babies who are attempting to develop their brains should come to a close.

JLW, Pittsburgh, PA 6/30/2017