Introduction
Autism is a diagnostic label applied to neurological
disorders of early childhood onset. It manifests as deficits
in communication and in other social interactive skills.
Considerable variability exists in the severity of disease
in autistic patients, with somewhat arbitrary distinctions
between autism and childhood disintegration disorder at one
end and delayed normal development at the other extreme.
Autistic patients will commonly show a wider variety of
clinical manifestations than implied by a single diagnostic
label.While many millions of dollars have been spent on
autism-related research, only a few studies have provided
important insights into the underling cause, prevention and
treatment of this disease. This talk will provide a brief
summary of generally accepted research views on autism and a
lengthier discussion of some of the more controversial
opinions. The argument will be presented that autism is
essentially an encephalopathy of stealth-adapted viral
origin. Research findings on a stealth-adapted virus that
arose from the species of monkeys used to produce poliovirus
vaccine will be summarized. Sequencing of this virus has
suggested specific therapeutic approaches to the treatment
of patients with autism and other stealth-virus related
clinical conditions. Preliminary clinical experience with
some of these approaches has been encouraging and indicates
the need for formal therapeutic trials. Studies also need to
be pursued into the modes of stealth-virus replication and
transmission of what may well prove to be a major threat to
the survival of mankind.
Generally Accepted Research Views on the Nature of Autism
1. Autism has a Genetic Component: This is apparent from the
higher incidence of autism among boys. It is also supported
by the relative concordance of disease among monozygotic
(genetically identical) twins compared to dizygotic
(genetically different) twins. Still there are numerous
examples where only one of two genetically identical twins
has the disease. Genetics may well be a contributing factor
to the expression of autism, but it is clearly not the only
component to this (or these) diseases.
2. Brain Abnormalities in Autistic Children: Head
circumference has been accepted as a marker of brain size.
While normal at birth, the head circumference of 1-2 year
old autistic children is reportedly slightly enlarged. Brain
imaging has also shown enlargements in certain regions of
the brain, most noticeably in parts of the cerebellum.
Equally impressive are various functional studies that show
deficits in brain activation upon certain types of sensory
stimulation and in blood flow patterns in autistic children.
The question arises whether these changes are a consequence
of autism, rather than its cause. Limited histopathological
studies on brain tissue from autistic patients support the
view that certain brain cells are damaged and/or do not
normally develop.
3.Biochemical Indications of a Prenatal Disorder. As
recently reported, elevated levels of one or more
neuropeptides are present in neonatal blood samples obtained
from children who subsequently were diagnosed as autistic.
The source of the elevated neuropeptides was presumed to be
the brain but this was not established. The actual levels of
various neuropeptides examined differed among autistic
children, but as a group the autistic children were readily
distinguishable from normal children. Somewhat confounding,
however, was that similar elevations were consistently also
found in blood samples collected from mentally retarded
children. Mental retardation had not previously been linked
with autism and clearly differs with respect to the smaller
than normal head circumference seen at birth.
Controversial Issues Relating to Autism
1. Autism is the Result of Vaccination. Reports of marked
clinical deterioration and even the initial onset of autism
within days of receiving a vaccination has prompted the view
that the vaccine has caused the illness. Initially the focus
was on diphtheria/petussis/tetanus (DPT) vaccine but more
recently it has been on live measles/mumps/rubella (MMR)
vaccine. In the case of measles, vaccine-derived viral
material has been seen using immunohistochemistry and
molecular based assays within hyperplastic lymphoid tissue
present in the gastrointestinal tract of autistic
children.Similar findings were found in non-autistic
children with lymphoid hyperplasia. Although there are
reasons for concerns with live viral vaccines, including the
finding of retroviral related reverse transcriptase activity
in MMR vaccines, a primary etiological role of measles
vaccine virus is not supported by data indicating prenatal
abnormalities. A detrimental effect of MMR vaccine has also
been dismissed with results of various epidemiological
studies failing to show statistically significant
correlation between vaccine usage and disease prevalence.
2. Autism is a Primary Biochemical Disorder. Urine analyses
on autistic children have shown markedly elevated levels of
various peptides as well as other types of metabolic
products.An inference is that the levels of these chemicals
would also be increased in the brain and that they somehow
interfere with normal brain function. A prime example is the
opiate-like peptides resulting from incomplete digestive
breakdown of casein and gluten proteins. This view is
bolstered by noticeable clinical improvements in some
autistic children when placed on a casein and gluten free
diet. Peptides from abnormal bacterial and fungal bowel
flora may also been suggested as having neuroregulatory
activity whose levels may be reduced by antibiotics. A role
for cell associated peptidase is suggested by unpublished
studies that peptidase IV inhibitory fragments may also be
present in the urine of some autistic children.
Autism: A Stealth-Adapted Viral Encephalopathy
I am proposing that autism is primarily a prenatal infection
that involves the brain and occurs in a genetically
predisposed individual. The infection renders the person
susceptible to further brain damage from vaccines and other
environmental factors. Several lines of evidence support the
stealth virus cause of autism. For example:
Blood samples from autistic children consistently induce a
readily identifiable cytopathic effect (CPE) using viral
culture methods adapted for the detection of stealth-adapted
viruses. Stealth virus testing of blood samples from
autistic children has been subjected to formal “double
blind” analyses. Furthermore, cerebrospinal fluid (CSF) and
gastrointestinal biopsy have similarly yielded positive
cultures.
There is good evidence for stealth virus infections among
family members of autistic children. Many of the family
members will, upon close questioning, reveal symptoms of
neurological and/or immunological dysfunction.
Autistic patients will not infrequently display positive
results in assays intended to detect conventional virus and
bacterial pathogens. As discussed below, such results can be
attributed to cross-reactivity with stealth virus
components.
When will the stealth virus theory of autism be accepted and
supported by i) researches, ii) Public Health authorities,
and iii) families with affected children. The answer to the
first point is when it is clearly proven that
stealth-adapted viruses, as presently defined, do exist as
novel pathogens. This challenge, as well as the goal of
eliciting official Public Health involvement, will occur
when the message gets across that the extensively sequenced
prototype stealth-adapted virus is atypically structured and
that it arose as a probable contaminant of poliovaccine
production. Finally, parents will begin to focus their
energies on the stealth-adapted viruses infecting their
children once they begin to see real clinical improvements
based onanti-stealth virus therapies.
Sequencing Studies on an African Green Monkey Derived Simian
Cytomegalovirus (SCMV)
These studies unequivocally establish the origin of an
atypically structured cytopathic virus as being from SCMV.
For certain regions of the stealth viral genome, there is
over 90% identity between the nucleotide sequences of the
stealth virus and that of the Colburn strain of SCMV. Yet in
other regions, the two viruses differ in a manner that is
best explained by genetic instability in viral replication
and by the selection of genetic changes that favor viral
survival and avoidance of immune recognition. Of particular
note is that the virus failed to evoke an inflammatory
reaction in either the patient from whom it has been
repeatedly cultured, or from the cats in which it induced
considerable brain damage. To date, the genes that would
otherwise encode the major antigens targeted by anti-CMV
cytotoxic T lymphocytes have not been detected. Nor do the
viral cultures react with antibodies against several
antigens shared by human and simian CMV.
Over 120,000 nucleotide sequence data have been compiled on
the stealth-adapted virus. Long regions of contiguous
sequences suggests the coding of somewhat truncated proteins
in comparison to the coding potential of the comparable
region ofthe human CMV genome. To help clarify the extent to
which these changes reflect the preexisting SCMV genome, or
are part of a mutational process occurring within a
genetically unstable stealth-adapted virus, sequencing is
underway on an authentic monkey-derived SCMV.
Even at this stage of the work, is abundantly clear that
stealth adaptation involves much more than simple
deletion/mutation of particular genes targeted by the
cellular immune system. For example, there is a striking
over representation of certain genes. Of particular
interest, is the finding of multiple copies of genes
implicated in the production of, and providing receptors
for, potent growth factors called chemokines and present
within the virus. This observation strongly suggests the
potential value of suppressing chemokine production in this
particular patient.
Another striking feature of the DNA analysis is the presence
of particular cellular genes adjacent to viral genes. A
prime example is the three copies of a cellular chemokine-related
gene within the viral genome. These virus-incorporated
cell-derived genes do not contain normal stretches of
non-coding sequences (introns) that are present in the cell
DNA. This would indicate that the recombination process
allowing cell-derived genes to become incorporated into a
replicating stealth virus had occurred at a partially
processed RNA, rather than at a DNA level. If so, it would
indicate a role for endogenouse reverse transcriptase in
stealth virus assembly and replication. Several other
cell-derived sequences are more readily amplified using
polymerase chain reaction (PCR) based assays performed on
the stealth virus culture than when performed on uninfected
cultures, suggesting that the sequences may have been
incorporated as part of the stealth virus replication
process.
Various bacterial-derived sequences have also been extracted
from the cultures. The bacterial sequences are of particular
interest since, along with additional data, it appears that
the virus is able to pass into, and, therefore, be
potentially metabolically empower and be transmitted by
bacteria. Taken together, the data are consistent with a
viral replicative process that allows the assimilation of
extraneous sequences of cellular, bacterial and possibly
fungal origins. Addressing this situation is particularly
urgent since among the potential activities of cell derived
genes, including chemokine-inducing and chemokine-receptor
genes, are the induction of malignant changes. The prospect
of highly infectious bacteria carrying cancer causing genes
is a serious concern that, so far, has been brushed aside by
those responsible for overseeing the Nation’s health.
Stealth-adapted viruses that have incorporated bacterial
sequences are referred to as “viteria.” Work is underway to
confirm that such organisms can be mistaken for actual
bacteria in conventional assays for such pathogens as
Borrelia burgdoferi, Mycoplasma incognitus, Chlamydia
pneumonia, etc. Many bacterial proteins have a propensity to
evoke allergic reactions offering a possible explanation for
such reactions among autistic children.
Stealth Adaptation as a Generic Process
CPE generally similar to that shown with the SCMV-derived
stealth-adapted virus has been consistently seen with blood
samples from many other patients. Most of these isolates do
not react particularly strongly with antibody and molecular
based probes that are highly reactive with the prototype
SCMV-derived stealth-adapted virus. This finding suggests
marked structural variability and probable multiple, diverse
origins of stealth-adapted viruses. Limited sequence and
antibody staining data on some of these additional isolates
are consistent with origins from other herpesviruses,
including Epstein-Barr virus and human herpesvirus-6; and
also from such diverse viruses as parvovirus, adenovirus and
enteroviruses. The addition of various live viruses to
positive stealth virus cultures can lead to enhanced CPE,
suggesting the possibility of reciprocal viral stimulation
and even the recombinant formation of new viral constructs.
This potentiating effect has been noted using live measles
and other viral vaccines. It is also reasonable to assume
that certain stealth viruses may retain some components that
would normally not be involved in evoking cellular immunity,
but in the presence of a powerful immune stimulant (such as
provided by DPT vaccine) could become a target for cell
damaging immunity.
A topic of interest is whether stealth-adapted viruses
cultured from autistic children will show any distinguishing
characteristics from those cultured from patients with other
disease manifestations. Given the overall similarity in the
CPE seen when tested blood samples from autistic and
non-autistic family members, it seems likely that a similar
virus is involved and that clinical manifestation relates to
sex, other genes and time and location of infection.
Implications for Patients with Autism
Specific testing for cell derived chemokine genes, as are
present in cultures of the prototype stealth virus, has yet
to be performed on stealth virus cultures from patients with
autism. Clinically, however, drugs that are known to down
regulate chemokines are finding increasing use in patients
with other stealth-virus associated diseases, including
depression, attention deficit and hyperactivity disorder
(ADHD) andCFS. Of particular interest are many of the
disease modifying anti-rheumatic drugs (DMARDS). Some
clinicians have also anecdotally noted symptomatic
improvement with Acyclovir, an anti-herpesviral drug.
Progress in this field will require disciplined clinical
trials with close monitoring of patients using both clinical
markers and semi-quantitative stealth virus cultures. In the
meantime, work needs to be continued on the development of
more specific therapies that are based on a more detailed
understanding of the mode of stealth virus replication.
Positive blood cultures is a sign of a body wide infection
that can potentially cause multi-organ damage (both as the
result of direct virus damage and an evoked auto-immune
response). Rather than being viewed narrowly as a
neuropsychiatric illness confined to the brain, autism
should be viewed as a generalized viral infectious process
that also involves the brain. Specific testing for endocrine
disorders, gastroenteropathy, liver damage, allergies, etc.,
should be part of the overall medical profile of any stealth
virus infected patient. The finding of a positive stealth
virus culture in a child is probably sufficient reason to
avoid the intense immunological stimulation associated with
DPT vaccine and also to not add extraneous infectious
viruses in the form of MMR and live poliovirus vaccine.
Acceptance of an infectious cause of autism can help explain
the occurrence of stealth-virus associated illness among
other family members. Certainly other family members should
be tested for infection. The socially difficult issue of
possible contagion to classmates, schoolteachers,
non-infected family members, etc., is better addressed than
denied.
Summary
Autism is a clinical label referring to a set of symptoms
that can occur as a result of infection with atypically
structured, poorly immunogenic (stealth-adapted) viruses.
This conclusion should help reorient the clinical approach
to the diagnosis, therapy and prevention of this illness.
*Lecture prepared to be given at Catalina Island, June 9,
2001, but unable to do so for family reasons.
What are Stealth-Adapted Viruses and Do They Exist
The accompanying article provides a recent review of stealth
viruses. Viruses are submicroscopic infectious agents that
replicate only within cells. They are comprised of an
essential nucleic acid polymer consisting of a linear string
of correctly ordered nucleotides that attaches to, and is
protected by, viral proteins whose amino acid sequences are
coded by the nucleic acid polymer.While viruses are
generally much smaller than bacteria, the major distinction
between these life forms is that at particular stages of
their life cycle, viruses will consist of either an RNA or a
DNA nucleic acid polymer. By contrast, bacteria will
consistently contain both DNA and RNA and usually many more
additional components involved in metabolic functions,
including protein synthesis, energy generation, formation of
a protective cell wall, etc. While some bacteria are still
dependent on human and/or animal cells for their
replication, most bacteria can function as free living
microorganisms.
Viruses were initially detected on the basis of the cellular
damage they induced when they co-opted cellular metabolic
processes to allow for their replication. Essentially, the
viruses drained the cells existence as they tended to their
own reproduction. The virus induced cell damage was referred
to a CPE. Some viruses induce a fairly distinctive CPE in
particular cell types. For other viruses, the CPE is more
subtle and may, in fact, not be seen in routine microscopic
examinations, or may be viewed as simply resulting from
unexplained toxicity of the material being tested for viral
activity.
Viruses can be further characterized by sequencing all or
parts of its nucleic acid polymer, and by using antibodies
that that selectively react with the proteins that
characterize the different types of viruses. These
techniques are more narrowly focussed on the detection of
viruses whose DNA or RNA sequences are known and whose
proteins have been used to generate specifically reactive
antibodies.For broader screening of as yet unknown viruses,
the tissue culture methods still provide a very powerful
tool. Molecular and immunological methods can then be used
to further characterize the cytopathic agent.
Using a combination of molecular, immunological and tissue
culture techniques, I was able to repeatedly culture a
cytopathic virus from a patient with an acute onset
neurological illness that has resulted in long term chronic
fatigue syndrome (CFS). Having seen the CPE caused by this
virus, it was possible to continually adapt the culture
method to shortened the period required for its appearance
and to promote its development within the cultures. It soon
became apparent that generally similar types of CPE could be
seen in cultures obtained from patients with other
neurological illnesses, including autism and behavioral
problems in children, depression and schizophrenia in adults
and neurodegenerative diseases in the elderly. Healthy
medical students, used as controls, were negative for the
marked changes being seen with patients’ samples.
Unfortunately, the work fell into the nationwide controversy
regarding the very existence of CFS as an illness. Moreover,
whereas the description of a CPE occurring in cultured cells
are understandable to those who work directly with viral
cultures, most physicians and other healthcare workers are
basically unfamiliar with virus culturing techniques.
Patient support groups also wanted an assay that would
differentiate patient with their particular clinical illness
from patients with other diseases. The finding of positive
cultures in “non-fatigued” patients, yet not in all patients
with CFS, was a blow to the initial support received from a
CFS patient group.
African Green Monkey Derived Simian Cytomegalovirus (SCMV).
Tissue Culture Cytopathic Effect (CPE). An important
hallmark of many, but not all disease causing viruses, is
there ability to alter the growth and overall appearance of
cells that they infect.
W. John Martin, M.D.,Ph.D.
Center for Complex Infectious Diseases
Rosemead CA 91770
Telephone (626)572-7288;
e-mail ccidlab@hotmail
Web address: www.ccid.org
