THE UNIVERSITY OF CHICAGO
Department of Psychiatry
MC 3077
5841 S. Maryland Avenue
Chicago, IL 60637
Child and Adolescent Psychiatry
Laboratory of Developmental Neuroscience
April 3, 2000
Honorable Dan Burton
Chairman
Committee on Government Reform
House of Representatives
Congress of the United States
2157 Rayburn House Office Building
Washington, DC 20515-6143
Dear Representative Burton and Colleagues:
Thank you for the opportunity to testify on the topic of
autism. I am speaking as the brother of the
late Kenneth Wade Cook who had many of the problems of children and adults with autism, as
a physician who cares for many patients with autism, and as a researcher trying to
increase our knowledge of the causes of autism and to increase our ability to treat this
devastating disorder.
I recall being an 8 year-old boy with a 2 year-old brother that my
family had just realized was not developing normally.
I remember the pain of my parents vividly. I
further recall that we went to a meeting where, to my recollection, we were told that
"patterning," a special diet, rebreathing through a mask, and related methods
still practiced today would cure his problems. I
remember our family being skeptical for part of the meeting. By the end of the meeting, we and the other
families in the group were sold on this treatment because it was too painful to accept
what we knew was happening. If there is
anything I have not forgotten, it is that hope is something essential in working with
children with severe challenges. I am
thankful to those who were interested enough in children to spend so much time with my
brother and my family. They knew that
providing us the tools to work to teach my brother the basics of communication and motor
skills was helpful and I suspect that many of them were practicing this method for the
same reason we were. They had to try.
I could complain about the 5 AM mornings in which it was physically
exhausting to perform the patterning, but I'm sure it was at least good training for the
schedule of a physician-scientist and provided a shared task for our family. However, I'm not pleased that there wasn't more
time spent teaching me to play with my brother instead of trying to teach him to read,
when it wasn't close to being an appropriate next step. Our family learned to accept and
love my brother deeply. I am thankful that
children today more opportunity for education due to Congressional legislation. Excellent community support was vital to my family
during my brother’s last years in St. Louis. Mostly
I miss him since his death at the age of 29. His
death remains as unexplained as his original problem, although the two are likely to be
related. It reminds me that there is
mortality as well as morbidity associated with autism and related developmental
disorders.
We have an extremely long way to go to provide full access to
adequate care for children, adolescents, and adults with autism. It is very difficult to confront attitudes as a
physician that I only suspected as a child. Insurance
companies, state agencies, school administrators, and other physicians continually turn
away from caring for people with autism. Much
more attention is given to paperwork than provision of care and services. This is not the main purpose of our meeting today,
but I can not speak without mentioning this. Although
many of the most severe problems are emotional and behavioral, insurance companies
discriminate against the best treatments by the most qualified providers, with the result
often being time lost from work for parents, depression in parents, and most importantly,
suffering would otherwise be treatable.
The needs of the patients and problems in the systems of care and
education have seemed overwhelming since I started my practice in the mid 1980s, so the
thought of an increase in the prevalence of autism is probably something I wouldn't want
to confront. However, comment on changes in
systems that are largely responsible for the apparent increase is appropriate. An increase in autism in Illinois schools has been
cited as evidence a rise in autism prevalence rates, but autism is still underestimated in
Illinois schools. The increase is based on
the introduction of autism as a possible educational classification in autism. In addition to many educational systems not
recognizing autism, many diagnosticians didn’t recognize it in the past. Autism spectrum disorders are only beginning to be
accurately estimated. Based upon its
widespread ethnic distribution, it has most likely been challenging people with autism and
their families for thousands of years, but it has taken us this long to recognize what it
is. Thus, the committee's ongoing work is
important and a sense of urgency is necessary to catch up for lost time.
This brings to mind the medical saying, "first do no harm." One harm worse than doing nothing was blaming
mothers because of their physical and emotional closeness to their children. Not only were individuals hurt by blaming mothers
for their child's autism, but we probably lost a couple of decades following an impression
of causation rather than focusing on the same science that was leading to improved
treatments in cancer and heart disease. Without
evidence to support a relationship between vaccinations and autism, we need to be careful
about wasting precious resources on another case of guilt by association. Mothers were guilty because they were physically
close to children with autism. Now
vaccinations are being blamed largely because they are given at the same time as the
regressions that occur for a substantial minority of children with autism (between the
first and second birthday). Certainly, GI
findings that have not been demonstrated to be specific for autism do not provide support
for MMR vaccinations as a cause of autism. Data
may be provided today which are credible in support of a connection, but the data to date
do not support the hypothesis of MMR vaccination caused autism.
It has been a privilege to be involved in the development of new
treatments for children with autism. Lost in
the media's overfocusing on "miracle" cures over the more than three-and-a-half
decades I have been involved, are small changes in our available treatments. Although limited to improving aggressive behavior,
anxiety, and depression, medications that potently inhibit the reuptake of serotonin into
nerve terminals (SSRIs)(e.g. Prozac, Luvox, Paxil, Zoloft, Celexa) have provided the first
medication class that reduces the core symptoms of repetitive behavior leading to distress
for many people with autism. Of course, it
isn't enough, but it demonstrates that improvements through development of effective
medications are possible. As far as research
challenges and needs are concerned, pharmacological treatment research needs to be
enhanced so that we have better data about whether each of these drugs works in autism,
for which symptoms, at what ages, and for which patients.
In addition, it would be extremely helpful to know which patients will worsen on
small doses and what treatments to provide such patients.
As many know, not all of our attempts to improve treatment have been
successful. A relatively classic story is
that of fenfluramine, originally thought to raise I.Q. and reduce symptoms of autism. After considerable work, fenfluramine was found to
be a good placebo. Although we were hopeful
that secretin would be serendipitous powerful treatment, at least two carefully controlled
trials have shown it to be similar in effect to fenfluramine in providing a good placebo
effect. Further studies are ongoing to
make sure a positive effect is not present under certain circumstances, but it may be
about to end up as part of the long history of good, honest attempts to hit a home run in
autism treatment that struck out. There is no
reason not to try, except that we have to be careful about the risks to the children and
the costs to the families if we overly promote treatments without evidence from controlled
trials.
There is a problem when thousands of doses of secretin from pigs
could be administered to children with claims of benefit while clinical trials to study
safety and efficacy were being delayed by federal policies against expediting research
review for secretin clinical trials. This
ironic situation allowed the supply of secretin to be depleted, thus delaying initiation
and completion of our multi-site trial.
Having several hats as brother, physician and scientist can be very
painful. I recall my anger as a child when
investigators found that patterning wasn't effective.
How could they do such a thing and how could I now be in their shoes in
contributing to data about the lack of efficacy of secretin? All I have to say is that I shed a tear when the
data were analyzed for secretin, much as I shed many tears when I came to the realization
that "patterning" was not going to let me know my brother without his severe
problems.
I suppose it is obvious why so much of my time is devoted to research
reaching down to basic mechanisms. On the one
hand, I am desperate to improve the situation for my patients, many of whom are reminders
of my brother. On the other hand, for some of
my patients I have seen medical treatments provide relief I didn't think possible before
our first use of Prozac in autism shortly after its release in 1988. By the way, there is no reason to have lengthy
discussions about who tried it first, since I know I had parents discuss it around the
same time or before professionals were considering it.
The riskiest thing for a physician-scientist to do is translational
research, especially when it is from the bedside to the bench. Basic science has a much more appealing
longitudinal logic. Clinical science has
relevance. As much as both are pioneering,
translational research often requires almost autistic perseverance. However, eventually the bridge has to be
crossed.
Our laboratory has worked on neurochemisty, neuroimmunology,
neuroendocrinology, neuroimaging, and neurogenetics of autism. The reason for our current focus on genetics is
that the data, not impressions, show it to be the most powerful influence in the etiology
of autism. It is not the only influence and
it is not a simple, single gene disorder. However,
it is a rare event in my lifetime to realize that suddenly that molecular genetic study of
autism spectrum disorders provides one of the best scientific opportunities in medicine. Of course, this would not be possible without the
considerable basic science advances and applied science advances ranging from sequencing
of the human genome, to development of rapid methods of genotyping, to the development of
powerful statistical approaches. It is new
for established researchers in other fields to be drawn into autism and related disorders
because of the scientific opportunity.
It is unlikely that gene therapy will be the result of genetic
research in autism. It is also unlikely that
genetics of autism will explain a relatively recent increase in measured autism
prevalence. The point of genetic research is to develop treatments that will correct the
missing or abnormal signals for a small set of nerve cells in the amygdala, hippocampus,
and cerebellum so that the nerve cells mature. If
we knew the signals, what has long been a too complicated puzzle of autism will become
simple enough for us to understand. Although
the simple idea is to provide gene therapy, oral delivery of more traditional small
molecules is likely to be more feasible and preferable.
Even more important has been the emerging voice of families of
children with autism. I can not begin to list
and thank the parents, brothers, sisters, aunts, uncles, and grandparents who are not only
taking on the extraordinary challenge of caring for their family members, but who are
speaking for people with autism who because of their communication problems are not as
able to speak for themselves as we wish they could.
The need to learn more about autism is self-apparent and the
scientific opportunities are abundant. The
challenges are in learning about something as complicated as the developing brain and
development of some of the most uniquely human qualities of higher level communication and
social behavior.
Two recent developments in the broader field of developmental
disorders show that complex situations may be better understood through molecular
genetics. The first is the finding of the
gene for FRAXA mental retardation. This is
very relevant to autism since a substantial proportion of children with FRAXA have autism
spectrum disorders. Although one wishes
knowledge of a gene will lead to new treatment sooner, the results of a decade of research
to understand the mechanism of this disorder is leading to an almost exponential growth in
understanding of complex interactions of molecules in the process of learning. Another development is the recent cloning of the
gene for Rett syndrome. This is actually one
of the most severe autism spectrum disorders. It
is notable that it is caused by a single gene, MECP2,
but that it has a course of regression in social behavior and communication between the
first and second birthday. Knowing the gene
has led to a breakthrough in the systematic approach to investigation of Rett syndrome in
terms of how it affects the development of the brain.
Study of both FRAXA and Rett syndrome will lead to basic knowledge about how autism
and related conditions develop.
Although we don't know the specific genes involved, several groups
have been finding evidence that an extra part of chromosome 15 leads to a high risk for
autism, especially if inherited from the mother. Although
responsible for less than 4% of cases of autism, these 15q11-q13 duplications, like Rett
syndrome and FRAXA, are likely to help us understand autism more generally. Several laboratories, including our own, are
searching for a gene in this region. As an
example of our concern about not wanting to waste precious resources, the probability of
there not being a gene in this region is about 5 in 100,000, but we're not sure yet. Of course, we'll have to get beyond regions with
likely autism genes to actually finding the specific genetic changes and then getting on
with the work of using the information to improve treatment. (More information about molecular genetic studies
and autism is available at our web site at: http://psychiatry.uchicago.edu/ldn ).
It's a good thing there are people doing good clinical research and
trying to improve educational and other interventions while we are working out the
fundamental causes. It's also good that
people are asking questions about prevention and even taking shots to improve medication
delivery, either trying to hit for average with medications like Prozac, or swinging for
the fences with an occasional secretin trial. However,
it's important not to think we have more of an effect than we can back with controlled
data. History teaches us that zeal without
skepticism may have negative consequences (e.g. false accusation of fathers of children
with autism who underwent facilitated communication).
The challenges of autism research are obvious. In terms of needs, I mostly want to thank Congress
for the appropriation of increased funds for biomedical research. All of the pertinent NIH institutes are now
engaged in active support of autism research. A
simple statement of needs is that there are many important and feasible questions about
autism not able to be asked with current resources. There
are not enough well-trained researchers in the field, partly because the area was almost
totally unfunded five short years ago. Most
importantly, questions that are being asked well and efficiently, such as in the area of
molecular genetics, are not being answered at an optimal rate given current funding in the
area. Again, this is not meant as a
criticism, but as a statement of scientific opportunity.
Thank you for the opportunity to communicate.
Sincerely,
Edwin H. Cook, Jr.,
M.D.
Associate Professor of Psychiatry and Pediatrics