Dr. Seller
2012-08-28 19:43:43 UTC
By MOISES VELASQUEZ-MANOFF
IN recent years, scientists have made extraordinary advances in
understanding the causes of autism, now estimated to afflict 1
in 88 children. But remarkably little of this understanding has
percolated into popular awareness, which often remains fixated
on vaccines.
So heres the short of it: At least a subset of autism perhaps
one-third, and very likely more looks like a type of
inflammatory disease. And it begins in the womb.
It starts with what scientists call immune dysregulation.
Ideally, your immune system should operate like an enlightened
action hero, meting out inflammation precisely, accurately and
with deadly force when necessary, but then quickly returning to
a Zen-like calm. Doing so requires an optimal balance of pro-
and anti-inflammatory muscle.
In autistic individuals, the immune system fails at this
balancing act. Inflammatory signals dominate. Anti-inflammatory
ones are inadequate. A state of chronic activation prevails. And
the more skewed toward inflammation, the more acute the autistic
symptoms.
Nowhere are the consequences of this dysregulation more evident
than in the autistic brain. Spidery cells that help maintain
neurons called astroglia and microglia are enlarged from
chronic activation. Pro-inflammatory signaling molecules abound.
Genes involved in inflammation are switched on.
These findings are important for many reasons, but perhaps the
most noteworthy is that they provide evidence of an abnormal,
continuing biological process. That means that there is finally
a therapeutic target for a disorder defined by behavioral
criteria like social impairments, difficulty communicating and
repetitive behaviors.
But how to address it, and where to begin? That question has led
scientists to the womb. A population-wide study from Denmark
spanning two decades of births indicates that infection during
pregnancy increases the risk of autism in the child.
Hospitalization for a viral infection, like the flu, during the
first trimester of pregnancy triples the odds. Bacterial
infection, including of the urinary tract, during the second
trimester increases chances by 40 percent.
The lesson here isnt necessarily that viruses and bacteria
directly damage the fetus. Rather, the mothers attempt to repel
invaders her inflammatory response seems at fault. Research
by Paul Patterson, an expert in neuroimmunity at Caltech,
demonstrates this important principle. Inflaming pregnant mice
artificially without a living infective agent prompts
behavioral problems in the young. In this model, autism results
from collateral damage. Its an unintended consequence of self-
defense during pregnancy.
Yet to blame infections for the autism epidemic is folly. First,
in the broadest sense, the epidemiology doesnt jibe. Leo Kanner
first described infantile autism in 1943. Diagnoses have
increased tenfold, although a careful assessment suggests that
the true increase in incidences is less than half that. But in
that same period, viral and bacterial infections have generally
declined. By many measures, were more infection-free than ever
before in human history.
Better clues to the causes of the autism phenomenon come from
parallel epidemics. The prevalence of inflammatory diseases in
general has increased significantly in the past 60 years. As a
group, they include asthma, now estimated to affect 1 in 10
children at least double the prevalence of 1980 and
autoimmune disorders, which afflict 1 in 20.
Both are linked to autism, especially in the mother. One large
Danish study, which included nearly 700,000 births over a
decade, found that a mothers rheumatoid arthritis, a
degenerative disease of the joints, elevated a childs risk of
autism by 80 percent. Her celiac disease, an inflammatory
disease prompted by proteins in wheat and other grains,
increased it 350 percent. Genetic studies tell a similar tale.
Gene variants associated with autoimmune disease genes of the
immune system also increase the risk of autism, especially
when they occur in the mother.
In some cases, scientists even see a misguided immune response
in action. Mothers of autistic children often have unique
antibodies that bind to fetal brain proteins. A few years back,
scientists at the MIND Institute, a research center for
neurodevelopmental disorders at the University of California,
Davis, injected these antibodies into pregnant macaques.
(Control animals got antibodies from mothers of typical
children.) Animals whose mothers received autistic antibodies
displayed repetitive behavior. They had trouble socializing with
others in the troop. In this model, autism results from an
attack on the developing fetus.
But there are still other paths to the disorder. A mothers
diagnosis of asthma or allergies during the second trimester of
pregnancy increases her childs risk of autism.
So does metabolic syndrome, a disorder associated with insulin
resistance, obesity and, crucially, low-grade inflammation. The
theme here is maternal immune dysregulation. Earlier this year,
scientists presented direct evidence of this prenatal imbalance.
Amniotic fluid collected from Danish newborns who later
developed autism looked mildly inflamed.
Debate swirls around the reality of the autism phenomenon, and
rightly so. Diagnostic criteria have changed repeatedly, and
awareness has increased. How much if any of the autism
epidemic is real, how much artifact?
YET when you consider that, as a whole, diseases of immune
dysregulation have increased in the past 60 years and that
these disorders are linked to autism the question seems a
little moot. The better question is: Why are we so prone to
inflammatory disorders? What has happened to the modern immune
system?
Theres a good evolutionary answer to that query, it turns out.
Scientists have repeatedly observed that people living in
environments that resemble our evolutionary past, full of
microbes and parasites, dont suffer from inflammatory diseases
as frequently as we do.
Generally speaking, autism also follows this pattern. It seems
to be less prevalent in the developing world. Usually,
epidemiologists fault lack of diagnosis for the apparent
absence. A dearth of expertise in the disorder, the argument
goes, gives a false impression of scarcity. Yet at least one
Western doctor who specializes in autism has explicitly noted
that, in a Cambodian population rife with parasites and acute
infections, autism was nearly nonexistent.
For autoimmune and allergic diseases linked to autism,
meanwhile, the evidence is compelling. In environments that
resemble the world of yore, the immune system is much less prone
to diseases of dysregulation.
Generally, the scientists working on autism and inflammation
arent aware of this or if they are, they dont let on. But
Kevin Becker, a geneticist at the National Institutes of Health,
has pointed out that asthma and autism follow similar
epidemiological patterns. Theyre both more common in urban
areas than rural; firstborns seem to be at greater risk; they
disproportionately afflict young boys.
In the context of allergic disease, the hygiene hypothesis
that we suffer from microbial deprivation has long been
invoked to explain these patterns. Dr. Becker argues that it
should apply to autism as well. (Why the male bias? Male
fetuses, it turns out, are more sensitive to Moms inflammation
than females.)
More recently, William Parker at Duke University has chimed in.
Hes not, by training, an autism expert. But his work focuses on
the immune system and its role in biology and disease, so hes
particularly qualified to point out the following: the immune
system we consider normal is actually an evolutionary aberration.
Some years back, he began comparing wild sewer rats with clean
lab rats. They were, in his words, completely different
organisms. Wild rats tightly controlled inflammation. Not so
the lab rats. Why? The wild rodents were rife with parasites.
Parasites are famous for limiting inflammation.
Humans also evolved with plenty of parasites. Dr. Parker and
many others think that were biologically dependent on the
immune suppression provided by these hangers-on and that their
removal has left us prone to inflammation. We were willing to
put up with hay fever, even some autoimmune disease, he told me
recently. But autism? Thats it! Youve got to stop this
insanity.
What does stopping the insanity entail? Fix the maternal
dysregulation, and youve most likely prevented autism. Thats
the lesson from rodent experiments. In one, Swiss scientists
created a lineage of mice with a genetically reinforced anti-
inflammatory signal. Then the scientists inflamed the pregnant
mice. The babies emerged fine no behavioral problems. The take-
away: Control inflammation during pregnancy, and it wont
interfere with fetal brain development.
For people, a drug thats safe for use during pregnancy may
help. A probiotic, many of which have anti-inflammatory
properties, may also be of benefit. Not coincidentally, asthma
researchers are arriving at similar conclusions; prevention of
the lung disease will begin with the pregnant woman. Dr. Parker
has more radical ideas: pre-emptive restoration of
domesticated parasites in everybody worms developed solely
for the purpose of correcting the wayward, postmodern immune
system.
Practically speaking, this seems beyond improbable. And yet, a
trial is under way at the Montefiore Medical Center and the
Albert Einstein College of Medicine testing a medicalized
parasite called Trichuris suis in autistic adults.
First used medically to treat inflammatory bowel disease, the
whipworm, which is native to pigs, has anecdotally shown benefit
in autistic children.
And really, if you spend enough time wading through the science,
Dr. Parkers idea an ecosystem restoration project,
essentially not only fails to seem outrageous, but also seems
inevitable.
Since time immemorial, a very specific community of organisms
microbes, parasites, some viruses has aggregated to form the
human superorganism. Mounds of evidence suggest that our immune
system anticipates these inputs and that, when they go missing,
the organism comes unhinged.
Future doctors will need to correct the postmodern tendency
toward immune dysregulation. Evolution has provided us with a
road map: the original accretion pattern of the superorganism.
Preventive medicine will need, by strange necessity, to emulate
the patterns from deep in our past.
Moises Velasquez-Manoff is the author of An Epidemic of
Absence: A New Way of Understanding Allergies and Autoimmune
Diseases.
http://www.nytimes.com/2012/08/26/opinion/sunday/immune-
disorders-and-autism.html?_r=1&pagewanted=all&pagewanted=print
Autism is caused by older dried up clean fantic liberal females
who don't let their kids play in dirt. The liberal females are
usually taking multiple rx drugs and recreational drugs of some
type. They don't cook often and they each a lot of packaged
dinners from Costco.
IN recent years, scientists have made extraordinary advances in
understanding the causes of autism, now estimated to afflict 1
in 88 children. But remarkably little of this understanding has
percolated into popular awareness, which often remains fixated
on vaccines.
So heres the short of it: At least a subset of autism perhaps
one-third, and very likely more looks like a type of
inflammatory disease. And it begins in the womb.
It starts with what scientists call immune dysregulation.
Ideally, your immune system should operate like an enlightened
action hero, meting out inflammation precisely, accurately and
with deadly force when necessary, but then quickly returning to
a Zen-like calm. Doing so requires an optimal balance of pro-
and anti-inflammatory muscle.
In autistic individuals, the immune system fails at this
balancing act. Inflammatory signals dominate. Anti-inflammatory
ones are inadequate. A state of chronic activation prevails. And
the more skewed toward inflammation, the more acute the autistic
symptoms.
Nowhere are the consequences of this dysregulation more evident
than in the autistic brain. Spidery cells that help maintain
neurons called astroglia and microglia are enlarged from
chronic activation. Pro-inflammatory signaling molecules abound.
Genes involved in inflammation are switched on.
These findings are important for many reasons, but perhaps the
most noteworthy is that they provide evidence of an abnormal,
continuing biological process. That means that there is finally
a therapeutic target for a disorder defined by behavioral
criteria like social impairments, difficulty communicating and
repetitive behaviors.
But how to address it, and where to begin? That question has led
scientists to the womb. A population-wide study from Denmark
spanning two decades of births indicates that infection during
pregnancy increases the risk of autism in the child.
Hospitalization for a viral infection, like the flu, during the
first trimester of pregnancy triples the odds. Bacterial
infection, including of the urinary tract, during the second
trimester increases chances by 40 percent.
The lesson here isnt necessarily that viruses and bacteria
directly damage the fetus. Rather, the mothers attempt to repel
invaders her inflammatory response seems at fault. Research
by Paul Patterson, an expert in neuroimmunity at Caltech,
demonstrates this important principle. Inflaming pregnant mice
artificially without a living infective agent prompts
behavioral problems in the young. In this model, autism results
from collateral damage. Its an unintended consequence of self-
defense during pregnancy.
Yet to blame infections for the autism epidemic is folly. First,
in the broadest sense, the epidemiology doesnt jibe. Leo Kanner
first described infantile autism in 1943. Diagnoses have
increased tenfold, although a careful assessment suggests that
the true increase in incidences is less than half that. But in
that same period, viral and bacterial infections have generally
declined. By many measures, were more infection-free than ever
before in human history.
Better clues to the causes of the autism phenomenon come from
parallel epidemics. The prevalence of inflammatory diseases in
general has increased significantly in the past 60 years. As a
group, they include asthma, now estimated to affect 1 in 10
children at least double the prevalence of 1980 and
autoimmune disorders, which afflict 1 in 20.
Both are linked to autism, especially in the mother. One large
Danish study, which included nearly 700,000 births over a
decade, found that a mothers rheumatoid arthritis, a
degenerative disease of the joints, elevated a childs risk of
autism by 80 percent. Her celiac disease, an inflammatory
disease prompted by proteins in wheat and other grains,
increased it 350 percent. Genetic studies tell a similar tale.
Gene variants associated with autoimmune disease genes of the
immune system also increase the risk of autism, especially
when they occur in the mother.
In some cases, scientists even see a misguided immune response
in action. Mothers of autistic children often have unique
antibodies that bind to fetal brain proteins. A few years back,
scientists at the MIND Institute, a research center for
neurodevelopmental disorders at the University of California,
Davis, injected these antibodies into pregnant macaques.
(Control animals got antibodies from mothers of typical
children.) Animals whose mothers received autistic antibodies
displayed repetitive behavior. They had trouble socializing with
others in the troop. In this model, autism results from an
attack on the developing fetus.
But there are still other paths to the disorder. A mothers
diagnosis of asthma or allergies during the second trimester of
pregnancy increases her childs risk of autism.
So does metabolic syndrome, a disorder associated with insulin
resistance, obesity and, crucially, low-grade inflammation. The
theme here is maternal immune dysregulation. Earlier this year,
scientists presented direct evidence of this prenatal imbalance.
Amniotic fluid collected from Danish newborns who later
developed autism looked mildly inflamed.
Debate swirls around the reality of the autism phenomenon, and
rightly so. Diagnostic criteria have changed repeatedly, and
awareness has increased. How much if any of the autism
epidemic is real, how much artifact?
YET when you consider that, as a whole, diseases of immune
dysregulation have increased in the past 60 years and that
these disorders are linked to autism the question seems a
little moot. The better question is: Why are we so prone to
inflammatory disorders? What has happened to the modern immune
system?
Theres a good evolutionary answer to that query, it turns out.
Scientists have repeatedly observed that people living in
environments that resemble our evolutionary past, full of
microbes and parasites, dont suffer from inflammatory diseases
as frequently as we do.
Generally speaking, autism also follows this pattern. It seems
to be less prevalent in the developing world. Usually,
epidemiologists fault lack of diagnosis for the apparent
absence. A dearth of expertise in the disorder, the argument
goes, gives a false impression of scarcity. Yet at least one
Western doctor who specializes in autism has explicitly noted
that, in a Cambodian population rife with parasites and acute
infections, autism was nearly nonexistent.
For autoimmune and allergic diseases linked to autism,
meanwhile, the evidence is compelling. In environments that
resemble the world of yore, the immune system is much less prone
to diseases of dysregulation.
Generally, the scientists working on autism and inflammation
arent aware of this or if they are, they dont let on. But
Kevin Becker, a geneticist at the National Institutes of Health,
has pointed out that asthma and autism follow similar
epidemiological patterns. Theyre both more common in urban
areas than rural; firstborns seem to be at greater risk; they
disproportionately afflict young boys.
In the context of allergic disease, the hygiene hypothesis
that we suffer from microbial deprivation has long been
invoked to explain these patterns. Dr. Becker argues that it
should apply to autism as well. (Why the male bias? Male
fetuses, it turns out, are more sensitive to Moms inflammation
than females.)
More recently, William Parker at Duke University has chimed in.
Hes not, by training, an autism expert. But his work focuses on
the immune system and its role in biology and disease, so hes
particularly qualified to point out the following: the immune
system we consider normal is actually an evolutionary aberration.
Some years back, he began comparing wild sewer rats with clean
lab rats. They were, in his words, completely different
organisms. Wild rats tightly controlled inflammation. Not so
the lab rats. Why? The wild rodents were rife with parasites.
Parasites are famous for limiting inflammation.
Humans also evolved with plenty of parasites. Dr. Parker and
many others think that were biologically dependent on the
immune suppression provided by these hangers-on and that their
removal has left us prone to inflammation. We were willing to
put up with hay fever, even some autoimmune disease, he told me
recently. But autism? Thats it! Youve got to stop this
insanity.
What does stopping the insanity entail? Fix the maternal
dysregulation, and youve most likely prevented autism. Thats
the lesson from rodent experiments. In one, Swiss scientists
created a lineage of mice with a genetically reinforced anti-
inflammatory signal. Then the scientists inflamed the pregnant
mice. The babies emerged fine no behavioral problems. The take-
away: Control inflammation during pregnancy, and it wont
interfere with fetal brain development.
For people, a drug thats safe for use during pregnancy may
help. A probiotic, many of which have anti-inflammatory
properties, may also be of benefit. Not coincidentally, asthma
researchers are arriving at similar conclusions; prevention of
the lung disease will begin with the pregnant woman. Dr. Parker
has more radical ideas: pre-emptive restoration of
domesticated parasites in everybody worms developed solely
for the purpose of correcting the wayward, postmodern immune
system.
Practically speaking, this seems beyond improbable. And yet, a
trial is under way at the Montefiore Medical Center and the
Albert Einstein College of Medicine testing a medicalized
parasite called Trichuris suis in autistic adults.
First used medically to treat inflammatory bowel disease, the
whipworm, which is native to pigs, has anecdotally shown benefit
in autistic children.
And really, if you spend enough time wading through the science,
Dr. Parkers idea an ecosystem restoration project,
essentially not only fails to seem outrageous, but also seems
inevitable.
Since time immemorial, a very specific community of organisms
microbes, parasites, some viruses has aggregated to form the
human superorganism. Mounds of evidence suggest that our immune
system anticipates these inputs and that, when they go missing,
the organism comes unhinged.
Future doctors will need to correct the postmodern tendency
toward immune dysregulation. Evolution has provided us with a
road map: the original accretion pattern of the superorganism.
Preventive medicine will need, by strange necessity, to emulate
the patterns from deep in our past.
Moises Velasquez-Manoff is the author of An Epidemic of
Absence: A New Way of Understanding Allergies and Autoimmune
Diseases.
http://www.nytimes.com/2012/08/26/opinion/sunday/immune-
disorders-and-autism.html?_r=1&pagewanted=all&pagewanted=print
Autism is caused by older dried up clean fantic liberal females
who don't let their kids play in dirt. The liberal females are
usually taking multiple rx drugs and recreational drugs of some
type. They don't cook often and they each a lot of packaged
dinners from Costco.