Unlocking the genetic secrets of autism

Intense and even fanatical resistance to vaccination against
childhood diseases is itself a significant public health problem.
Opponents have blamed vaccines for everything from allergies and
diabetes to cancer and autism.



A recent study of abnormalities in the DNA of children with autism
spectrum disorders (ASDs) should finally put to rest the claims of some
activists, mainly parents of affected children, that vaccines cause
these conditions.



An international group of scientists reported in June in the journal
Nature that patients suffering from ASDs had in their genes a higher
incidence of mutations in the form of deletions, insertions or
duplications of segments of DNA than unaffected control subjects. These
findings offer the possibility of both early detection and the
development of drugs to target and neutralize the specific biochemical
abnormalities caused by the mutations.



Autism is a developmental disorder characterized by deficits in
social interaction and communication; a limited range of activities and
interests; and often the presence of repetitive, stereotyped behaviors.
Cognitive development can range from above-average to profound
intellectual disability. Autism disorders are diagnosed in 1 in 110
children in the U.S. and are found in four times as many boys as girls.



Although it has been known that ASDs run in families the underlying
genetic determinants have been elusive, but the Nature article offers
some new insights. Drawing on data from 60 research institutions in 12
countries, the researchers analyzed the genes of 996 children with ASDs
and 1,287 children without the condition. They found that each affected
individual carried his or her own unique assortment of mutations.



This contrasts with the situation in sickle-cell anemia, for example,
where the disease is most commonly caused by a unique mutation -- a
change in one specific nucleotide of DNA, which in turn causes a single
amino acid change -- in a gene that codes for the protein of hemoglobin.
(Genes comprise DNA, which is a template that, after an intermediate
step, directs the ordering of various amino acids into proteins.)



Where and when do these ASD mutations arise? Professor Daniel
Geschwind, chief of human genetics and director of the Center for Autism
Research and Treatment at the UCLA School of Medicine, said the
findings suggest that the "tiny genetic errors may occur during
formation of the parents' eggs and sperm," and that these mutations are
conveyed into the DNA of offspring. "The autistic child is the first in
their family to carry that variant. The parents do not have it."



If ASDs arise spontaneously in this way, still unresolved is why they
appear to be so heritable: The occurrence of ASDs in siblings is about
100 times greater than the rate at which the disorders affect unrelated
people in the population. Perhaps there is a predilection in some people
toward the tiny genetic errors in eggs and sperm that give rise to ASDs
and that would tend to affect all their offspring.



It is unclear how the beleaguered parents of autistic children will
react to this new information about the genetic basis of autism spectrum
disorders. In the past many have resisted such explanations, preferring
instead to blame adverse reactions to vaccines as the cause in spite of
persuasive evidence to the contrary.

The basis for this misapprehension is a 1998 article by a British
physician that claimed a link between the measles-mumps-rubella (MMR)
vaccine and the autistic symptoms. However, the findings were never
duplicated and were subsequently discredited in the medical community
worldwide, and the article was withdrawn by the journal that had
published it.



Last month's article in Nature offers important new scientific
insights into the molecular basis of autism spectrum disorders. One of
the lead researchers predicted, "Just knowing about these genetic
changes can help the families come to terms with why their child has
autism." That remains to be seen. But equally important are the broader
implications of this research -- namely, the alleviation of misplaced
concerns in the broader community about childhood vaccines, and greater
awareness of the public health benefits of wider immunization.



Dr. Henry Miller, a physician and molecular biologist, is a
fellow at Stanford University's Hoover Institution. Dr. Elizabeth Whelan
is president of the American Council on Science and Health.