Roulette William Smith, Ph.D. details a potentially ground breaking theory that purports to unravel the mystery surrounding the underlying causative factors of autism spectrum disorders, schizophrenia, and a host of other mental and physical illnesses in his paper entitled, “Inferring an Autovirulent Epigenetic Etiology for the Autism Spectrum and Schizophrenia*.” Dr. Smith’s theory originated from insights gleamed from three co-cited research articles (discussed in the manuscript) combined with a synthesis of other relevant research using logistic reasoning and logistic intelligence.
Smith’s theory is complicated and does not lend itself to a brief overview. Some may find the manuscript a difficult read without at least some background in the neurosciences, infectious diseases, immunology, genetics, logic, methodology, and philosophy of science. I only intend to provide a generalist overview that highlights the major points. Those who interested are strongly encouraged to read the entire manuscript (check the end of this report for a link to download).
Dr. Smith kindly allowed The Behavioral Medicine Report to publish the latest version of his manuscript so check the end of this review for a PDF download. Please note that the manuscript is not a final version so a few areas need citations (noted by ###) or small formatting changes.
In “Inferring an Autovirulent Epigenetic Etiology for the Autism Spectrum and Schizophrenia,” Dr. Smith guides the reader through a skillful interdisciplinary presentation of key discoveries from the scientific fields of mathematical logic, infectious diseases, epidemiology, biology, psychology, neuroscience, immunology, and genetics that ultimately tie together seemingly disparate findings into a succinct, coherent, and testable autovirulent theory of disease.
Epstein-Barr Virus (EBV) is a common and ubiquitous herpes virus that infects a majority of the world’s population. In the United States, as many as 95% of adults between 35 and 40 years of age are infected (Wikipedia). Check Table 1 of Dr. Smith’s manuscript for a list of diseases currently believed to be associated with the EBV. Although EBV is a DNA virus, the Autovirulent Theory of Autism and Schizophrenia postulates that stress activatedEBV releases secondary small-RNA particles (called EBER-1 and EBER-2) that, in turn, hijack and modify the ‘genetic code’ and, in some instances, human DNA. These transmittable and infectious small-RNA particles are called autovirions, and the process of infecting a host cell is called autovirulence. Stress hormones, called glucocorticoids (and especially cortisol), provide the signal for EBV to release its autovirions.
Importantly, Dr. Smith notes that humans are susceptible to autovirulent processes at virtually any stage of life… from the earliest beginnings (germ cell division), in the womb, or even into adulthood. He believes that autovirulence contributes significantly to the risk of developing a wide spectrum of human developmental, psychological, and physical disorders. Although Smith hypothesizes that autovirulence may explain autism, schizophrenia, Guillain-Barre Syndrome, Lou Gehrig’s disease, Tourette’s syndrome, and post-polio syndrome, his manuscript does not provide much evidence for the latter three disorders. Autotoxins (infectious protein molecules that lack DNA or RNA, which include prions) and molecular mimicry are discussed as other potential methods for viruses and transmissible particles to infect host cells. Smith reminds readers that viruses are capable of vast mutations (e.g., the Bishop-Varmus ‘oncogene’ hypothesis) so it should not be surprising that the specific type of small-particle RNAs frequently can cause DNA changes and some will be capable of autovirulent actions while others will not.
Smith’s notion of “context-specificity” determines whether the viral by-products result in pathological consequences. The host organism’s unique cellular developmental stage, immune functioning, and current psychosocial/environmental situation (i.e., stress and anxiety) make up the contextual environment. Autovirulence produces a wide range of diseases (or none at all) dependent on the context in which it occurs. For example, a fetus (9 – 38 weeks) would be expected to take a much different developmental course than a full grown adult following autovirion invasion of their physiological system. In fact, context-specificity predicts that autovirulence can produce very different diseases in the exact same womb conditions, dependent on the specific developmental stage of the unborn child. In short, Dr. Smith proposes that context-specificity provides the basis for the vast spectrum of diseases believed to be caused by the EBV.
Epigenetics is an additional important concept. Dr. Smith defines epigenetics quite succinctly as “heritable or propagated alternative states of gene expression, molecular function, or organization specified by the same genetic instructions (DNA sequence)” (pgs. 7-8). Dr. Smith explained in a personal communication that this subtle and succinct definition subsumes previous definitions of epigenetics used in genetics and molecular biology, yet generalizes the notion to allow for DNA to be a repository of long-term memory in brain and the immune system. This is discussed in the manuscript as “DNA as a LTM” hypothesis. Smith’s theory advocates that the EBV attempts to indirectly modify the host organism’s DNA code through epigenetic processes, which can be very difficult for scientists to detect since the DNA sequences have not changed (only the gene functions/expression has changed). Essentially the small-particle RNAs hijack the host’s DNA like a B-2 stealth bomber: it arrives covertly and its presence is only known due to the devastating consequences! Smith describes these as ‘hit-and-run’ and ‘beneath-the-radar’ consequences. In this case of human disease, immune system and organ dysfunction are the result. This might explain why researchers have such a difficult time identifying genes specific to various disorders. Interestingly, Dr. Smith believes that autovirions can positively affect human evolution depending on how they alter gene expression. His theory also suggests that human evolution theory may need to be updated.
In summary, Dr. Smith hypothesizes that EBVs release small particle RNAs into the human system during periods of intense stress and decreased immune functioning. The context in which they occur largely determines their effectiveness to produce pathological consequences. When pathology does result, the etiological origins are very difficult to detect due to the epigenetic nature of the DNA transformation.
Keep in mind that the above represents a theoretical argument, albeit one grounded in previous established research that needs to be empirically validated. No worries here as Dr. Smith’s theory produces specific, testable, and falsifiable hypotheses, several of which are detailed in his manuscript.
Here is sample of important questions and predictions raised by Dr. Smith’s theory:
- Is Down Syndrome facilitated by the mother’s stress levels rather than to “aging eggs?”
- Should we expect an increase in EBV-associated diseases in light of the current economic recession?
- Should physicians routinely assess (and appropriately treat) women’s anxiety during pregnancy to decrease risk of infant diseases?
- Will veterans of the current wars experience an increased prevalence of various psychological or physical disorders or will their children have increased rates of developmental disorders, such as Autism?
- Research to investigate the role of MMR vaccines in Autism should be abandoned if Smith’s theory is true that Autism starts before exposure to vaccines.
- Researchers should further investigate the role of maternal exposure to mercury.
- Autism should occur higher rates in the regions between Tropic of Cancer and Tropic of Capricorn due the hyperendemic (occurs at a high rate, yearlong) availability of the EBV in these regions.
- DNA is the storage mechanism for long-term memories, coined as “DNA as a LTM” hypotheses.
I hope that this report helps Dr. Smith’s important theory gain traction within the research community. I encourage our readers to forward this manuscript to interested colleagues, professors, and researchers.
Download the manuscript here.
Download Dr. Smith’s vita here.
*Smith, R.W. (2009). Inferring an autovirulent epigenetic etiology for the autism spectrum and schizophrenia. Unpublished manuscript available at The Behavioral Medicine Report: http://www.bmedreport.com/archives/1411