By Claire I. Viadro, MPH, PhD

Neurological disorders, autoimmune diseases—they seem to be everywhere these days. Scientists writing in Neurology in 2007 estimated that the burden of neurologic illness affects “many millions of people in the United States.”¹

Autoimmune illness, too, is at epidemic proportions—nearly 24 million Americans as of 2012.² These trends are disturbing enough in their own right, but even more disturbing is the general scientific apathy about why the surge in these diseases is occurring.

Why do the causes of these alarming epidemics remain “underrecognized and underaddressed?”³

Stephanie Seneff is one of the all-too-rare scientists who is trying to ask the questions and connect the dots. Dr. Seneff⁴ is a senior research scientist at the MIT Computer Science and Artificial Intelligence Laboratory with an illustrious career and lengthy publication record.

Of late, she has been using computer science and natural language processing (NLP) techniques (NLP is a field of computer science, artificial intelligence, and linguistics) to delve into the impact of environmental toxins on human health.

She has developed some particularly convincing hypotheses relating to autism and, more recently, cancer. At the Third International Symposium on Vaccines,⁵ presented in March 2014 as part of the 9th International Congress on Autoimmunity, Dr. Seneff was one of 15 speakers invited to present scientific research by the Children’s Medical Safety Research Institute⁶ (CMSRI) on the adverse health effects of aluminum adjuvants and aluminum-adjuvented vaccines.

She discussed “a role for the pineal gland in neurological damage following aluminum-adjuvented vaccination.” Along the way, she made many fascinating connections between various strands of her recent work, briefly summarized in this article.

The Critical Role of Sulfate

Dr. Seneff persuasively makes the case that neurological brain diseases have a common origin that begins with an insufficient supply of sulfate to the brain. Sulfate is the oxidized form of sulfur. Dr. Seneff has argued that systemic sulfate deficiency “may be the most important factor in many of the health issues facing us today.”⁷

I’ll get to her thoughts on why so many people are deficient in sulfate in a moment, but suffice it to say that one of the consequences of insufficient sulfate in the brain is that it impairs the brain’s ability to eliminate heavy metals and other toxins. To make matters worse, those same toxic metals also interfere with sulfate synthesis. The net result can be an accumulation of cellular debris.

How do our brains get rid of cellular debris? Dr. Seneff cited recent work showing that sleep is crucial in this regard.⁸ Sleep is the brain’s “housekeeper.”

This housekeeping takes place in the lysosomes. (Lysosomes—the cell’s waste disposal system—are filled with enzymes that break down unwanted materials.) However, the lysosomes cannot perform their important clearing work without sulfate, specifically heparan sulfate.

Heparan sulfate belongs to the family of glycosaminoglycans or GAGs—complex polysaccharides that provide structural integrity to cells. Heparan sulfate regulates many different biological functions, including ion and nutrient transport as well as molecular signaling cascades for most of the body’s cells.

It also plays an important role in fetal brain development.⁹ The role of heparins and heparan sulfate as “endogenous antioxidants” protecting against damaging free radicals was recognized over 20 years ago.¹⁰

Interesting evidence of what happens when heparan sulfate is deficient comes from human and mouse studies of autism. In one study, “designer” mice engineered to have impaired heparan sulfate synthesis in the brain displayed all the classic features of autism, including sociocommunicative deficits and stereotypies.¹¹

To understand this area of autism research, it is helpful to visualize the ventricles in the brain. The ventricles—a “communicating network of cavities filled with cerebrospinal fluid (CSF)”¹² —consist of two lateral ventricles, the third ventricle, the cerebral aqueduct, and the fourth ventricle.

A 2013 study in Behavioural Brain Research found heparan sulfate deficiency in the subventricular zone of the lateral ventricles of four autistic individuals. The authors posited that this “may be a biomarker for autism, and potentially involved in the etiology of the disorder“¹³ [emphasis added]. Other studies have identified heparan sulfate depletion in the third ventricle.¹⁴

Enter the Pineal Gland

A notable feature of sulfate is that it is difficult to transport.¹⁵ Dr. Seneff’s extensive work on sulfur deficiency has led her to consider the important but perhaps underestimated role of the pineal gland in the transport process. The pineal gland is a neuroendocrine organ of the brain that resides in close proximity to the ventricles, as seen in the following illustration.

Figure 1. The brain and the pineal gland

A key role of the pineal gland is to synthesize and secrete melatonin, which controls the sleep/wake cycle.¹⁶ Dr. Seneff suggests that one of the critical purposes of melatonin, in turn, is to deliver sulfate to the neurons at night during sleep. In her words, melatonin is clearly a “sulfate delivery system.” Dr. Seneff outlined this intricate and elegant delivery system as follows:

1. With sunlight exposure serving as a catalyst, the pineal gland builds up supplies of sulfate by day, storing it in heparan sulfate molecules.
2. The pineal gland produces melatonin in the evening, transporting it as melatonin sulfate to various parts of the brain, including the third ventricle, where the melatonin releases the sulfate into the CSF.

The association of autism with heparan sulfate depletion in the lateral and third ventricles^{17, 18} now gets more interesting, because the tip of the third ventricle is encased in the pineal gland. The pineal recess is in fact the “main site of penetration of melatonin into the CSF.”¹⁹ In other words, under normal circumstances the pineal gland delivers melatonin sulfate to the third ventricle, which then diffuses the sulfate throughout the CSF. In addition, melatonin not only transports sulfate but also is an outstanding antioxidant and binds toxic metals to help dispose of them. It may come as no surprise, then, that melatonin impairment has been implicated in autism.

In healthy individuals, melatonin also plays an important role in inducing REM sleep, which may be the most important stage of sleep. Interestingly, Alzheimer’s disease is associated with reduced REM sleep and a calcified pineal gland. Sleep disorders are also linked to autism as well as other neurological diseases, including depression, schizophrenia, ALS, Parkinson’s disease, and others.

Your Pineal Gland and Heavy Metals

If one recognizes that heavy metals play a part in the modern-day epidemic of neurological diseases, then part of the explanation for the sleep disorders encountered in various neurological diseases may be that both aluminum and mercury (thimerosal) disrupt the pineal gland and its ability to make sulfate. When the pineal gland’s ability to make sulfate is impaired, this, in turn, reduces production of melatonin, all-important for adequate and healthy sleep. The pineal gland is particularly susceptible to aluminum and other heavy metals because it is not protected by the blood-brain barrier and has a very high blood perfusion rate.

The pineal gland’s vulnerability to aluminum is illustrated in a 1996 paper showing that the concentrations of aluminum in the pineal gland were “consistently observed” and “markedly higher” than in other brain tissues examined (pituitary, cortex, and cerebellum).²⁰ Returning to the link between the pineal gland, heavy metals, and sleep, a telling fact gleaned by Dr. Seneff from the national Vaccine Adverse Event Reporting System (VAERS) is that insomnia occurs more often as an adverse reaction to aluminum-containing vaccines than to vaccines not containing aluminum.

Scientists are taking note of the fact that we live in an “age of aluminum,” with aluminum exposure occurring through vaccines as well as multiple other channels.^{21, 22} Moreover, although many experts would have us believe that the question of thimerosal and vaccine safety went away after federal agencies issued lukewarm recommendations to reduce its use as a vaccine preservative in the early 2000s, Dr. Seneff noted that thimerosal is still very much relevant.

Why Some Children May Be More Prone to Vaccine Damage

She called attention to a 2013 paper that reminds us that thimerosal not only is not found in nature but is a “designer” mercury compound created by humans that is the most toxic nonradioactive metal—”even more toxic than lead to human fetal and neuronal cells.”²³ Bringing things full circle back to sulfur/sulfate, Dr. Seneff pointed out that the article makes an important link between autism and sulfation, concluding that children with abnormal sulfation chemistry (among other factors) may be particularly susceptible to the toxic effects of the thimerosal in flu and other childhood vaccines.²⁴

In fact, due to expanded recommendations for flu shots in pregnant women and young children, exposure to thimerosal through vaccination has remained widespread in the US, and more than half of all flu vaccine doses are still thimerosal-preserved.²⁵ Incredibly, the authors of the 2013 paper note the following:

“Estimates are that the maximum lifetime exposure to [thimerosal] a vaccinated person may receive is now more than double what it would have been had the pre-2000 vaccination schedule been maintained.”²⁶ [Emphasis added]

Dr. Seneff has done a lot of investigations using the VAERS database, which—despite its limitations—can be very informative. She notes that concurrent with the aggressive peddling of thimerosal-containing flu shots and other aluminum-containing vaccines, there has been a rise in reporting of both vaccine adverse events and autism spectrum disorders. She described one careful analysis of the VAERS database.

In a graph that speaks for itself (Figure 2 below), she plotted the number of VAERS reports mentioning three types of adverse events (autism, pervasive developmental disorders or PDDs, and anxiety disorder) against the total burden of two heavy metals (aluminum and mercury) in vaccines according to the current vaccine schedule. One can immediately see that the adverse event and heavy metals lines are quite similar. Moreover, both lines show a sharp spike around the year 2000, which is when the burden of aluminum and thimerosal increased. Dr. Seneff commented that while aluminum and thimerosal are each bad enough on their own, they also work synergistically to cause harm.

Figure 2. Link between reports of vaccine adverse events (VAERS database) and aluminum (Al) and mercury (Hg) burden in current vaccine schedule (Figure kindly provided by Nancy Swanson)

The Role of Sunlight

Returning once again to the topic of sulfate, Dr. Seneff underscored the important and neglected fact that sunlight is absolutely essential for human health because of its role in catalyzing sulfate production. We will be sulfate-deficient if we do not get enough sun. The pineal gland plays an important role in this process. Specifically, endothelial and neuronal nitric oxide synthase—both of which are present in the pineal gland—produce sulfate from reduced sulfur sources catalyzed by sunlight.

When this process is impaired through lack of sunlight exposure, the result is sulfate deficiency and—where a serum sulfate deficiency is present—an individual will also have an impaired ability to dispose of aluminum.²⁷ Aluminum accumulation in the pineal gland over time will disrupt sulfate supplies to the brain by interfering with the pineal gland’s ability to make sulfate. High-SPF sunscreens are one way in which the body can accumulate not-insignificant amounts of aluminum through skin absorption. Sunscreens contain aluminum nanoparticles, which are more dangerous than larger-sized aluminum particles and highly destructive in the brain.

A 2012 study found that nanoalumina destroyed mitochondria (thus severely depleting ATP, the body’s energy source), induced autophagy and programmed cell death in brain endothelial cells, and decreased expression of tight-junction proteins, thereby contributing to elevated blood-brain barrier permeability.²⁸ The nanoparticle effects were persistent and damaging. Thus, contrary to popular opinion, use of sunscreen is neither beneficial nor safe. (Dr. Seneff noted in passing that wearing sunglasses is also a terrible idea.)

Sunlight May Be Protective Against Autism

Dr. Seneff further assessed the importance of sunlight by compiling data from demographic studies in the 50 states (Table 1).

Table 1. Correlation of sunlight exposure and autism in public school students in 50 states (grades 1–6, 2007–2008)

Demographic	Pearson Correlation Coefficient	Category
Number of clear days	-0.40	Sunlight exposure
Rainfall and latitude	+0.34	Sunlight exposure
Vaccination rate	+0.38	Aluminum, mercury

 

Public schools in the US keep track of the number of students enrolled in each grade, and they also keep track of the number of students enrolled in programs specifically targeting autism. Using a ratio of these numbers, Dr. Seneff and co-investigators calculated a measure for autism in each state (using grades one to six for the 2007-2008 school year). They also obtained data for weather-related factors, using these as proxies for sun exposure (e.g., number of clear days and a combination variable capturing latitude and rainfall) and looked at states’ vaccination rates as a proxy measure for aluminum and thimerosal exposure.

They then calculated Pearson’s correlation coefficients as a way of understanding the strength of the relationship (or correlation) between sunlight exposure and autism. (Correlation coefficients range from -1.0 to 1.0, and a coefficient that is close to zero signals a weak relationship.) Bearing in mind that correlation does not necessarily mean causation, their analysis nonetheless produced correlations suggesting that sunlight is protective against autism, although other factors also clearly explain some of the variability.

One of the ways that the protective effect of sunlight exposure makes sense is recognizing the critical role that vitamin D plays in sulfate homeostasis. A study in mice found that activated vitamin D prevented sulfate wasting from the kidney in urine, and mice engineered to have defective vitamin D receptors (or with vitamin D deficiency) had significantly reduced serum sulfate levels, which were associated with sulfate depletion in the skeleton. Children with autism have high sulfate in their urine but low serum sulfate levels, which clearly indicates both generic sulfate deficiency and vitamin D deficiency.

Glyphosate: The Elephant in the Room

Dr. Seneff began paying attention to glyphosate after she had been intensely researching autism for five or six years. Glyphosate is a broad-spectrum systemic herbicide (known to the world under its trade name Roundup®). Among its many nefarious health effects, glyphosate disrupts the way the body manages sulfur.

In the process of examining all the known toxic chemicals in the environment and assessing which one(s) would be most likely to be causal for autism—given the specific comorbidities associated with autism—Dr. Seneff found that glyphosate matched up almost perfectly.

Both glyphosate and autism are associated with low melatonin, impaired sulfur metabolism (and low serum sulfate), low vitamin D, sleep disorders, disrupted gut bacteria, and more. Glyphosate—already a very dangerous chemical on its own—causes aluminum to be much more toxic. Glyphosate and aluminum can be viewed as “partners in crime,” working synergistically with one another. This partnership plays out in several ways:

1. First, glyphosate preferentially kills beneficial bacteria in the gut, which allows pathogens such as C. difficile to overgrow. Not only does this lead to leaky gut syndrome, but C. difficile produces something called p-Cresol, a phenolic compound that is toxic to other microbes via its ability to interfere with metabolism. (C. difficile is one of only a few bacteria able to ferment tyrosine into p-Cresol.) As it happens, p-Cresol also promotes aluminum uptake by cells. P-Cresol is a known biomarker for autism and is also an important factor in kidney failure,which leads to aluminum retention in tissues and eventually to dementia.
2. Glyphosate also serves to increase aluminum toxicity by “caging” aluminum to promote its entry into the body. Glyphosate promotes calcium uptakeby voltage-activated channels, which allow aluminum to gain entry as a calcium mimetic. Aluminum then promotes calcium loss from bones, contributing to pineal gland calcification.
3. Bringing melatonin back into the discussion, glyphosate interferes with what is known as the shikimate pathway. Although humans do not have the shikimate pathway, our gut flora do, and we depend on our gut flora to supply us with essential amino acids and many other things. Disruption of the shikimate pathway in our gut results in depletion of tryptophan, which is the sole precursor to melatonin. Besides needing melatonin to transport sulfate into the brain, we also need melatonin to reduce heavy metal toxicity. Where supplies of melatonin are adequate, melatonin will bind to aluminum, cadmium, copper, iron, and lead, and reduce their toxicity. Where melatonin is low, a lot of damage can result.

Roundup® is the number one herbicide in use in the US and, increasingly, around the world. Unfortunately, its use has increased further in lockstep with “Roundup-Ready” genetically engineered crops, including genetically modified (GM) mainstay crops such as soy and corn.

Dr. Seneff believes that when children are overexposed to glyphosate, especially through consumption of the GM foods that are widely prevalent in the American diet, they are more likely to react badly to vaccination. To illustrate this point, Dr. Seneff and Nancy Swanson plotted a graph showing autism trends in the US (as measured by autism rates in the US school system), adverse vaccine reactions reported to the VAERS system, and glyphosate application to GM corn and soy crops in the US (Figure 3). As can be seen, the trends overlap almost entirely, presenting “tantalizing links” between these variables. Dr. Seneff infers from these findings that glyphosate is making vaccines far more toxic than they would otherwise be.

Figure 3. Autism, glyphosate, and vaccine reactions in the US (Figure kindly provided by Nancy Swanson)

Summary

Taken together, the body of evidence elegantly assembled by Dr. Seneff supports her hypothesis that the epidemic levels of autism (and other diseases such as Alzheimer’s disease) currently seen in the Western world are caused by a severe deficiency in sulfate supplies to the brain. Under optimal circumstances, the pineal gland can synthesize sulfate stimulated by sunlight and deliver it via melatonin sulfate to the brain. However, aluminum, mercury, and glyphosate are working synergistically to derail this process, and sunlight deficiency (exacerbated by the misguided use of sunscreens containing aluminum nanoparticles) is further contributing to the pathology.

About the Author

Claire Viadro, MPH, PhD, is a professional writer and editor with two advanced degrees in public health. Her work has included serving as past editor of Autism Science Digest magazine; co-editing Bugs, Bowels, and Behavior: The Groundbreaking Story of the Gut-Brain Connection; and authoring or coauthoring over 20 peer-reviewed publications primarily focused on women’s health.