BIOMEDICAL
BY James Jeffrey Bradstreet, MD, MD(H), FAAFP
W
hen I was asked to answer this
question for The Autism File,
it seemed like a straight shot.
Anyone can find a standard definition
of autism at their community library or
on the Internet at countless sites, but
that isn’t what you really want to know.
I also know autism is not a simplistic or
even homogeneous disorder. Rather,
it represents a complex array of gene-
environment interactions that in turn
create unique subtypes that may overlap
in some ways while being very distinct
in others. This demands a rigorous
evaluation through a search of unique
disease markers that can help lead us into
a better understanding of each child’s
individual needs. That all sounds rather
intimidating to both doctors and parents
– and not surprisingly so. Doctors are
used to what is referred to as “usual and
customary practice,” and what we are
talking about is the attempt to profile
a child’s specific and unique disorder.
There is no usual autism treatment,
and there is only one FDA-approved
intervention for the agitation effects of
autism (risperadone); beyond that there is
nothing approved.
As a result, most of you got about as
far as the diagnosis when suddenly the
resources and solutions being offered
by the mainstream of medicine dried up.
Perhaps you were referred for behavioral
therapy to find a 2-year waiting list. But
more than likely you were told to let
Two things have kept me focused throughout this journey with my son and thousands of other sons and daughters
struggling to find their way back to wholeness. Are these great medical secrets I keep to myself? No. Really they
have as much to do with any other aspect of life as they do with autism. These are hope and persistence.
8 THE AUTISM FILE | www.autismfile.com | info@autismfile.com REPRINTED WITH PERMISSION © THE AUTISM FILE
the school system handle your child’s
needs. Occasionally that works fairly well,
but, in general, school systems suffer
from a serious lack of both financial and
personnel resources, making it highly
unlikely they could respond effectively to
your child’s developmental needs without
a lot of outside help – from you.
However, we are finding ways to
demystify at least some parts of the
underlying medical problems, while
finding they are frequently highly
responsive to our medical, nutritional,
and behavioral interventions. But the
actual question really plaguing your heart,
your mind, and your soul is this: what
happened to my precious child? And
after that question comes the next of a
long series, which become wrapped in
guilt, fears, sadness, and even panic. The
second question has to be: what can I do
to help my child?
I know these questions too. Not just
as a doctor, but as a father. I have stayed
awake at night asking myself all of these
countless questions – even the ones most
people are afraid to talk about like: will
he ever come back to me or is this all a
hopeless waste of time and money? Two
things have kept me focused throughout
this journey with my son and thousands
of other sons and daughters struggling
to find their way back to wholeness. Are
these great medical secrets I keep to
myself? No. Really they have as much
to do with any other aspect of life as
they do with autism. These are hope and
persistence.
A long time ago I read several books
on success. It seemed logical enough.
If you wanted to succeed you should
learn from others who had actually
done it. In one of those books was this
quote from Dale Carnegie: “Most of
the important things in the world
have been accomplished by people
who have kept on trying when there
seemed to be no hope at all.” This
is perfect. It merges together the key
to success for any venture or quest you
lay before it. That doesn’t mean you are
guaranteed success – far from it. Most
truly successful people fail over and over
again. But it most assuredly is a guarantee
you won’t succeed without these two on
your side.
On my desk is a solid bar of metal with
this quote carved into it: “Never, Never,
Never Give Up.” While that is not an
exact quote from Winston Churchill, it
is close enough. Most people give little
thought anymore to one of England’s
darkest hours. It was a time where people
huddled in fear in underground subway
tubes praying for safety and that they
might just survive. It was time of dread
and mortal consequences. Churchill’s
words were not merely inspirational; they
acknowledged a choice of survival lay
before the English people. They needed
to hear those words when they needed
them the most.
ISSUE 31 2009
 Those are the same words you must
carve into your psyche because, for
most families, autism is like the London
Blitz. Day after day of bad news is piled
on top of more bad news. The bombs
keep falling. The school fights you over
the education plan, your insurer refuses
to pay for your child’s medical care,
your spouse feels neglected, your other
children feel abandoned, your career (if
you still have one) suffers, you cannot
remember the last time you had fun, or
you have no idea what sleep is because
your little one always wakes up screeching
at 1:00 AM. The Blitz just keeps coming
day after day. When you reach this level
of despair you empathize with the feelings
of the war-shattered Londoners during
those darkest hours of 1940-41.
This gets me to my first useful
definition of autism: autism is a war. It
is a war being waged against your child
and your family. Unless you fight back
you are guaranteed more casualties and
greater destruction. I had the opportunity
to serve in the USAF early in my career.
That whole military experience has served
me well as I have taken on my son’s
personal battle with autism and also the
thousands of other children who have
crossed my path. To some extent thinking
militaristically helps you plan. We will talk
more about this later.
But autism is not just a metaphorical
war within your family; it is an
immunological battle taking place in the
gut and brain of your child. When we set
out to answer the questions about what
has happened to your child we quickly
find a large body of scientific evidence
involving the abnormal regulation of the
immune system. Unfortunately, we cannot
examine the brain like we might a sore
throat or a skin rash. It stays sealed away
behind the armor-plate of the skull and
inside the blood-brain barrier. This is why
autism has been categorized, since its
first observations 70 some years ago, as
a behavioral disorder. We can see those
manifestations of the illness – we cannot
see the brain to assess its degree of
inflammation or test it to see if toxins are
present.
So who are the friendlies and who
are the enemies in this combat zone?
Sadly it seems some of your child’s own
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defenders have defected and gone over
to the enemy’s side. When immune
cells lose their tolerance of the body’s
own cells we call that autoimmunity.
Researchers at Vanderbilt Medical School
recently published direct evidence of the
nature of the combat inside the brain1.
In their landmark study of autism brain
transcriptomics (the process of measuring
what the DNA is making to learn what is
really happening) they stated this: “…
these expression patterns appear to be
more associated with the late recovery
phase of autoimmune brain disorders,
than with the innate immune response
characteristic of neurodegenerative
diseases.” This is generally consistent with
the brain studies of the Johns Hopkins
group that showed very significant
inflammatory brain disease at the time of
autopsy from children with autism who
drowned2. To build on this, researchers in
Chicago found dramatically higher levels
of the inflammatory immune marker TNF-
alpha in the spinal fluid than in the blood
of children with autism3. This means the
inflammatory response was greater inside
the brain than outside the brain in the
rest of the body. Almost 11 years ago a
team in England found elevated levels
of neopterin in the urine of children with
autism4. Neopterin is produced when
immune cells turn on – typically as in
autoimmune disorders. We have observed
a similar pattern and will be publishing
this in the near future.
This makes the autoimmune
combat zone a likely critical feature
of your child’s complex symptoms and
problems. Inflammation in the brain
would be expected to increase the
risk of seizures, and in a study looking
at magnetoencephalographic (MEG)
patterns, over 80% of children with
the regressive subtype had abnormal
epileptiform (seizure-like activity on
EEG) findings5. This autoimmune disorder
would also be expected to be at least
partially responsive to anti-inflammatory
medications or interventions. While
carefully controlled studies are lacking,
various immune modifying agents have
been discussed in the autism literature.
These include intravenous infusion
of human immunoglobulin derived
antibodies (IVIG) 6, high dose steroids
On my desk is a solid bar
of metal with this quote
carved into it: “Never,
Never, Never Give Up.”
as in Landau Kleffner Syndrome 7,
spironolactone (a potassium-sparing
diuretic with anti-inflammatory
properties) 8, and pioglitazone (a diabetes
drug with anti-inflammatory effects) 9.
All of these diverse medications and
therapeutic agents have one thing
in common: they down-regulate
inflammation and reduce the autoimmune
response in the body. The fact that
immune modifying agents are often
effective, at least in open-label trials and
from anecdotal observations of numerous
physicians, supports the hypothesis that
an underlying immune mechanism is
contributing to autism symptoms.
My belief, derived from the science
we have today, is that most often autism
represents the behavioral symptoms of
a primary inflammatory or autoimmune
brain disorder. But the brain, while the
main symptom generator for the core
autism complex of symptoms, is not the
only target of this immune dysregulation.
An immunological battle is being fought
on at least two fronts: both the brain
and the gastrointestinal tract are under
attack. The pattern of gastrointestinal
inflammation is distinct from both Crohn’s
disease and ulcerative colitis (collectively,
IBDs)10. Exactly what this means is, as
of yet, unclear. Despite this, it is our
observation that the inflammation seems
to respond to similar treatments as the
other IBDs.
One of the weapons used by immune
cells to target what they detect as an
invader (which, as discussed, could be
healthy brain cells) is the generation of
free radicals. These are oxidizers (typically
unstable molecules with unpaired
electrons), which when present in excess
is called oxidative stress. Free radicals are
harmful to normal cells and can trigger a
death mechanism inside cells. Numerous
studies have demonstrated increased
levels of oxidation in autism11. Dr. Ming
and colleagues in New Jersey found
increased urinary isoprostane (a marker
9
 BIOMEDICAL

From left to right: 1. Dr. Bradstreet at the research laboratory. 2. Adriana’s team at the Science Fair award celebration: Adriana, Dr. Bradstreet,
David Mancini (dad), Jacquie Mancini (mom), Alanna Apap, BCBA, and Andrea Soffici, paraprofessional. 3. Adriana and Dr. Bradstreet

of fatty acid – cell membrane oxidation)
in autism cases12. We use this as a marker
of both inflammation and oxidation
since these two effects go hand in hand.
Our own research in conjunction with
Laboratoire Philippe Auguste in Paris,
France confirms these observations, as
well.
Inflammation and oxidative stress have
broad effects on the body and when left
in place over extended time will create
disruptions in how the brain forms, the
ability of mitochondria (cell organelles)
to produce energy, how food is digested,
and how the body defends itself from
infections. This would seem to be a
battle on several fronts happening all at
once, and that can truly be challenging
and overwhelming for us as parents and
doctors to understand and respond to.
Unlike how penicillin treats strep
throat, there are no magic bullets or
perfect pills that can extinguish autism.
Even good anti-inflammatories may
need to be used in combination or with
IVIG, as well as with other treatments
to repair gut flora. The dysregulation
of the immune system leaves the gate
open for yeast and unhealthy bacteria
to take over – often after a series of
antibiotics for respiratory tract or ear
infections. Over and over again we find
evidence of harmful bacterial and yeast
overgrowth (dysbiosis). This has been
She has insights not only into who she is now, but where she has
come from. Here is a soldier who can look to the battle won and
truly appreciate what has been restored back to her.
10 THE AUTISM FILE | www.autismfile.com | info@autismfile.com REPRINTED WITH PERMISSION © THE AUTISM FILE
documented with sophisticated bacterial
gene studies by the group headed by
Sid Finegold13. Treatment of the yeast
and clostridia bacteria typically results in
significant gains, and both antifungals
and anti-clostridia antibiotics are actively
being evaluated in formal studies with
our group in association with Dr. Doreen
Granpeesheh’s team at the Center for
Autism and Related Disorders and Dr.
Finegold’s group at the LA Veterans
Hospital and UCLA Medical Center.
Imagine a combat zone where the
generals (parents) deploy their troops
(physicians, therapists, teachers,
assistants, etc.) to defend against an all-
out assault from all sides. Now imagine
one of them didn’t hear the inspirational
speech about never giving up and
decided the fight was just too hard and
surrendered. No matter how strong the
defense is to the right flank, if the left
one collapses, the battle and, perhaps,
the war will be lost. So this brings me
to another critical definition: autism
is a team effort. The ground we are
all defending is the mind and health of
a child. We do not have the luxury of
quitting when we are tired or even when
we are broke. The stakes are simply too
high and the cost of losing unimaginable.
This seems like a good place to
introduce a hero in the autism war. If
autism had a medal of honor this child and
her team of supporters would absolutely
be worthy of the award. You will get to
know Adriana more in The Autism File, so
I won’t detract from her and her family’s
perspectives. Her issues are not that
uncommon, but her response to immune
therapy was dramatic and a cause for
hope for all of us. This child had evidence
of that autoimmune brain disorder
reflected by autoantibodies to critical
brain proteins. She had the inflammation
and oxidative stress, and with the support
and help of her parents, teachers, and
therapists we took on this battle. Now
her autism is gone due to the combined
effects of IVIG and really good behavior
therapy (ABA). These days I receive the
most incredible emails from this little
angel. I recently surprised Adriana when
she won an award at her local school
science fair. I drove the 90 minutes just to
enjoy her recovery and successes. Later
that night she wrote me, and I want to
share a part of it here with you: “It’s hard
to believe that you made that trip for me.
I am glad that you did because unless we
got to hang out together we wouldn’t
know about each other. You are a good
singer and dancer. I never knew that. Plus
you are totally cool (I had to put that in –
of course). Your kids are lucky. I know that
I am not supposed to bug you with the
emails (this is a General Mom instruction
– not mine) but when I had autism I was
not even able to share with you. Now I
can, so please don’t get annoyed.” Isn’t
that amazing? She has insights not only
into who she is now, but where she has
come from. Here is a soldier who can look
to the battle won and truly appreciate
ISSUE 31 2009

Find a doctor with an open
mind, a listening ear, the
experience and wisdom
to guide the medical
interventions, and one with
a heartfelt desire to help
your child.
what has been restored back to her. So do
you think her emails bug me? Absolutely
not! Instead they are like those words of
Churchill inspiring me to press on so more
children can share in this kind of success.
Her parents built a combat-ready force to
take on the battle of recovering this child.
That team is discussed more in the article
“Adriana: Coming Full Circle at Autism
One” by Jacquie Mancini, General, Mom,
and a winner, in this same issue of The
Autism File.
To summarize: what do we know?
 Autism is a war being fought on many
fronts all at once.
 The battle is for your child’s mind,
health, and future.
 Your child’s own immune system is
dysregulated, and typically forming
autoimmune reactions towards the
gut and the brain.
 Immune activation creates oxidative
stress, which in turn leads to
impairment of normal body chemistry
and weakening of mitochondria.
 Winning the battle requires
persistence and hope.
 It also requires a knowledgeable
team equipped with all the therapies
required.
Now, it’s time for you to put aside your
fears, your doubts, and your feelings
of helplessness and hopelessness and
become the General in your own child’s
battle to recover from autism. Get
educated. Come to biomedical autism
conferences (there is so much more
to learn than what I could fit into one
article). Learn about ABA and sensory
integration therapies. Study the IEP rules
ISSUE 31 2009 REPRINTED WITH PERMISSION © THE AUTISM FILE info@autismfile.com | www.autismfile.com | THE AUTISM FILE
(educational plan and your child’s legal
rights to an appropriate education) and
Dr. Bradstreet graduated from
the University of South Florida
advocate, advocate, advocate for your
College of Medicine and received his
child. Find a doctor with an open mind, a
residency training from Wilford Hall
listening ear, the experience and wisdom
to guide the medical interventions, and
USAF Medical Center. As a flight
surgeon, he was involved in aerospace
one with a heartfelt desire to help your
medicine research, and he has
child.
extensive experience and training in
It isn’t easy, but it is important to your
child’s future. It is unknown how much
environmental medicine and toxicology.
He is involved in autism-related
any child can recover. Most can become
outcome studies and environmental
far healthier, experience less abdominal
research with the University of
pain, and gain a better quality of life.
Washington and UCLA and serves as a
Some can recover to the point where
adjunct professor of child development
they fully integrate into life and go
and neuroscience at Southwest College
onto productive lives. Others will suffer
of Naturopathic Medicine in Tempe,
with lifelong disabilities that will require
Arizona. Dr. Bradstreet is the founder
someone else to be there for them.
and director of the International
Regardless of the outcome, persistence
Child Development Resource Center
gives you the best odds of winning. And
(www.icdrc.org). His son, Matthew,
you must remember the words of Winston
is recovering from autism with the
Churchill: NEVER, NEVER, NEVER,
combined help of biomedical and
NEVER GIVE UP (he actually did say it
behavioral interventions.
four times).
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