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A Modern Biology Lesson for President Trump, and a Plea for Smarter Directions in Autism Causation Research

1/23/2017

1 Comment

 
Picture

Since vaccines have clearly not contributed to the increase in autism, what questions should we should be asking instead?



President Donald Trump
The White House
1600 Pennsylvania Avenue NW
Washington, DC 20500

January 23, 2017

Dear President Trump,

As the mother of two children with severe, nonverbal autism, I must give you credit. While most politicians ignore the devastating and costly autism crisis that has swept our country, you have been unafraid to voice your concern. The tremendous surge in serious neurodevelopmental pathology over the past three decades has led to what is now one of our nation’s greatest public health and social services predicaments. And yet we still have few explanations for what lies behind this grim phenomenon.

Given the persistent vacuum of information and people’s rather understandable desire to make sense of inexplicable tragedies and hardships playing out in more than a million homes across the states, it’s not terribly surprising that attractive, if superficial, theories have taken root, even in the face of overwhelming evidence against them.

One hypothesis, with which you may be flirting, is the idea that vaccines cause autism. Another idea posits that we are all essentially delusional—that autism is perfectly natural, and rising rates are simply an artifact of awareness, broader diagnostics and re-labeling of conditions that once bore other names, such as childhood schizophrenia. The collective data from epidemiological and basic research show emphatically that neither of these views is correct. Vaccines do not cause autism. And the majority of the autism surge cannot be explained by heightened awareness and diagnostic shifts. Nevertheless, in their respective and somewhat diametrically opposed corners, these fictions stubbornly persist.

I’m writing this letter because we must move past this dead-end false dichotomy and approach the autism question with both the urgency and biological rationalism it deserves. You and your staff seem to have the urgency, now let’s nail the biological rationalism.

Research is increasingly demonstrating that the impairments we call autism are disorders of brain development and function, particularly with respect to circuits that underlie learning, and that the dysfunctions begin to show their hands in early fetal development. While some direct somatic prenatal impacts raise the risk for autism, such as fetal exposure to certain anti-seizure medications, some infections, and prematurity, those factors appear to explain only a fraction of the overall cases.

Many researchers are quick to call the unaccounted-for remainder “genetic” mainly because autism is without doubt strongly heritable, meaning in most cases it likely stems from glitches within the egg and/or sperm of the parents, and not from proximal blows to the developing brain (as is the case with Zika microcephaly).

Many counter, however, that autism can’t be genetic because genes don’t change that quickly or easily, and moreover we can’t seem to find genetic causes for more than about 10% of autism cases. And that is true—our millenia-old human genes can’t explain the increase in autism, and the DNA-scouring approach has largely come up empty-handed.

The problem is this “genes or environment” view of autism is premised on a faulty, incomplete and outdated view of biology, and is therefore misguiding our federal approach to the issue. The past ten years have seen a sea change in how biologists think about heritability, moving away from simple genetic determinism, which still regrettably dominates autism research, and toward a multifactorial systems view embracing the importance of many aspects of genome and gamete biology, in addition to other developmental factors. If we want to understand autism, our research must flow from biological realities, not outmoded hyper-simplistic notions.

Here’s a quick biology lesson. DNA is but a single piece of an extraordinarily complex molecular apparatus within gametes that holds sway over later neurodevelopment. Normal brain growth and function depends on a galaxy of itty-bitty on-off switches lying between genes, several “epigenetic” processes, which include chemical tags within and atop DNA helping control gene expression, and cytoplasmic molecules such as tiny RNAs that help define final protein products, among other factors. As the field of genomic toxicology has discovered, these crucial molecular processes can be vulnerable to disruption.

With this vulnerability in mind, I seed-fund pilot projects investigating generational impacts of fetal exposure to certain toxicants, including tobacco (via maternal smoking pervasive in the second half of the 20th century), certain pregnancy drugs, and other surprising exposures such as maternal general anesthesia. This work is based in part on my experience discovering I had been exposed in utero to acute doses of powerful synthetic steroid hormone administered to my mother when pregnant with me (and my eggs). I believe my two children’s catastrophically abnormal neurodevelopment likely stems from unforeseen errors laid down by aberrant hormonal signaling in my vulnerable egg precursor cells. I have found many other autism parents with this same exposure story, and many other autism parents with stories of prenatal exposures to other toxicants of interest. This concept has come to be known as the “Time Bomb” hypothesis of autism because it links forgotten gamete exposures in the parents to mystifying pathology in children some decades later. If we accelerate autism research as we should, I believe this hypothesis warrants attention.

Another important and related field for research relates to exposures in the pre-conception window. Taken as a whole, studies suggest that subtle impairments in sperm or in the conceptus (perhaps precipitated through certain forms of assisted reproductive technology) may contribute to autism risk. In one study, for example, abnormal epigenomic marks were found in the sperm of fathers of children with autism. It’s critical to better understand what exposures or manipulations may perturb the late-stage gametes and elevate the risk for dysregulated neurodevelopment.

A third area for improved research involves direct effects on central nervous system development. Some studies suggest that early exposure to certain chemicals, including endocrine-disrupting compounds, may have adverse and persistent effects on healthy brain development. Though some work is being done in this field already, there are many chemicals that warrant more thorough review for developmental safety.

While vaccines—like all pharmaceutical drugs—carry some risks, there is no reason to attribute the stunning surge in autism to them. Allow me to offer a few of the reasons:

  • The vaccine hypothesis cannot explain the strong heritability of autism.
  • The vaccine hypothesis cannot explain the very early neurodevelopmental derangements seen in autism.
  • The vaccine hypothesis cannot explain the sustained rates of autism even after removal of allegedly offending ingredients.
  • The vaccine hypothesis cannot explain the demographics of autism: particularly the somewhat higher rates in certain areas and socio-economic sections.
  • The vaccine hypothesis cannot explain the 4:1 male: female ratio seen in autism, the most replicated finding in autism research.
  • The mercury-in-vaccines hypothesis cannot explain why even subsistence gold miners and those children in their vicinity, and others who are exposed to strongly elevated amounts of mercury do not have elevated rates of autism.
  • The vaccine hypothesis cannot explain the findings from neuroscience finding functional impairments in circuits and connectivity.
  • The vaccine hypothesis cannot explain the broadly consistent timing of detectable autism onset, usually before 12 months but almost always before 18 months. Just as schizophrenia usually develops after adolescence absent any contemporaneous exposure.
  • Extensive epidemiological research has not supported the vaccine hypothesis. Even organizations that believe vaccines cause autism have funded research which has shown no relationship between vaccines, thimersal and autism behaviors.
  • If anything, vaccines help prevent autism and neurodevelopmental damage by preventing dangerous brain infections that in the not very distant past had not infrequently caused lifelong intellectual disability (this includes rubella, measles, mumps, poliovirus, varicella and more). The link between maternal illness, including rubella and influenza, during pregnancy and increased risk of autism has been established in the scientific literature.

Mr. President, you are an expert businessman. You do not waste time and you do not waste money. But further inquiry into the autism/vaccine connection is a waste of time and money at exactly the moment we should be urgently hunting down more promising theories, some of which are described above. Americans deserve answers, and this is no time for either complacency (autism is all “natural diversity”) or unscientific dead-ends (vaccine blaming). I believe considerable progress on autism is firmly within our grasp.

Thank you for your sincere concern about the autism crisis, which deserves a place as one of America’s top policy priorities, and your consideration of these ideas.

Very truly yours,
Jill Escher


Jill Escher is founder of the Escher Fund for Autism, the mother of two children with nonverbal forms of autism, an active advocate for autism causes in the San Francisco Bay Area, and a housing provider to adults with autism and developmental disabilities. Learn more about her hypothesis at the Escher Fund’s science education website, www.GermlineExposures.org.
1 Comment
Anne K. Ross link
1/23/2017 06:04:12 pm

Wonderful letter! Thank you for your work and philanthropy.

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    Jill Escher, Escher Fund for Autism, is a California-based science philanthropist and mother of two children with severe autism, focused on the question of how environmentally induced germline disruptions may be contributing to today's epidemics of neurodevelopmental impairment. You can read about her discovery of her intensive prenatal exposure to synthetic hormone drugs here. Jill is also president of Autism Society San Francisco Bay Area.

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