TEUVO RANTALA, a Finnish nutrition researcher, thought life was just fine. He
had a great job with the country鈥檚 Olympic track and field team, a happy home
life and a sweet two-year-old son. But gradually his son Samu changed, becoming
withdrawn and uncontrollable. When not smashing up the house in a wild rage,
Samu would sit alone, fiddling obsessively with curtains or light switches.
He would not look at his father.
Doctors confirmed Rantala鈥檚 worst fears. Samu was autistic鈥攏ear the top
of the scale. Instantly, all those private dreams that a father has for a son
were destroyed. It was unlikely that Samu would ever learn to tie a shoelace let
alone talk or read. The tantrums would only get more destructive as Samu grew in
strength but not in mind.
鈥淚t was terrible, terrible,鈥� Rantala remembers. 鈥淢y wife said if nothing
changed, we could not cope鈥攈e would have to go into a mental
丑辞蝉辫颈迟补濒.鈥�
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That was five years ago. This past winter, Samu has been learning to skate
and ski. He cannot speak, but he is using signs. Most importantly for a parent,
he is calm and happy to be hugged. 鈥淣ow we have an almost normal home life
together,鈥� sighs Rantala.
What caused the change? Rantala credits a controversial theory that in some
cases autism may be the roundabout result of an intestinal complaint. It goes
like this. Evolutionarily speaking, humans have only recently added cow鈥檚 milk
and wheat to their diet, and many people have trouble digesting some of the
proteins they contain such as casein and gluten. Instead of being broken down to
their constituent amino acids, they are partially broken down into peptides.
These peptides have structures that mimic the many opiate-like hormones and
neurotransmitters used by the brain. In autism, goes the theory, the peptides
leak across the gut wall into the blood and eventually through the tough
membrane that protects the brain, where they muck up the brain鈥檚 development. By
putting his son on a strict casein and gluten-free diet, Rantala claims he was
able to halt the cycle of damage鈥攁lthough he says the damage that has been
done will probably never be completely repaired.
A few things separate this story from countless others in which patients or
patient鈥檚 parents claim that something in the diet triggered their particular
brand of mental disorder. First, new genetic evidence suggests that the cause of
autism is far more complicated than any one had ever imagined. That helps give
the rogue peptide theory鈥攁n elaborate idea by anyone鈥檚 reckoning鈥攁
new patina of plausibility. Second, one of the parents, Paul Shattock, just
happens to be trained as a biochemist
Autism is certainly in the news at the moment, partly because of a feeling
that the number of cases is rising, that it is part of a modern 鈥減lague鈥� in
developmental illnesses which includes attention deficit syndrome, hyperactivity
and dyslexia. And partly because the effort to crack the genetic basis of the
illness has just borne its first fruit. In March, a seven-country consortium
announced in the journal Human Molecular Genetics (vol 7, p 571) that
they had found locations on at least six different chromosomes, each possibly
containing multiple genes, with potential links to autism.
Marie Bristol-Power, who coordinated the effort from the National Institute
of Child 91色情片 and Human Development, near Washington DC, warns that the
results still need replicating and that the real breakthrough will come only
when the actual genes have been sequenced and their roles identified. But, she
says, the sheer speed at which the gene work has moved ahead has amazed
everyone.
Still, not everyone is enamoured of high-powered genetics research. For
Shattock the results just prove 鈥渢he bleeding obvious鈥濃�攖hat a number of
genes combine to make some infants particularly susceptible to developing
autism.
Until 1974, Shattock was doing conventional research on plant biochemistry.
But then, like Rantala, he had a son diagnosed as autistic. At two-and-a-half,
the boy knew all his nursery rhymes and was even beginning to read, then
suddenly everything went into reverse. Shattock threw himself into the task of
making scientific sense of the condition.
At first, he simply maintained a database of autism research, but as he
listened to others speculating about the peptide-poisoning link, he realised he
had the skills to do the research himself. The theory was so fringe that he
could get virtually no funding. Indeed, at the time many psychiatrists were not
even convinced that autism was a brain disease rather than the result of abusive
parenting. Shattock was forced to 鈥渂usk it鈥�, eventually giving up his
lectureship at the University of Sunderland in northeast England and surviving
by selling fund-raising booklets and doing the odd spot of locum teaching.
Despite the hardships, he believes he has made his own breakthrough.
Psychiatrists have been baffled by autism since it was first recognised in
the 1940s as something more than just another form of mental retardation. The
condition is characterised by a complete withdrawal from social contact, a lack
of speech and a general unawareness. Autistics tend to focus on inappropriate
details鈥攁ttracted like Samu to the swish of curtains or a flicker of
light鈥攐r find comfort in mindless rocking, hand-flapping and elaborate
rituals. Many autistics are retarded but others have normal IQs. There is no
obvious damage to their brains, although the cerebral hemispheres, which
organise perception and are the seat of higher functions like speech, are often
larger than normal, while the cerebellum, which coordinates movement, can be
much smaller. Another oddity鈥攚hich makes it difficult for parents to
control their autistic children鈥攊s that they do not seem to respond to
punishment or reward, as if numb to normal pleasure and pain.
Originally, just 1 in 10 000 children were thought to have the disorder.
However, with a gradual broadening of the diagnosis to take in both very
severely affected children and many of those with a milder form of autism known
as Asperger鈥檚 syndrome (where the symptoms may be no more than extreme physical
and social clumsiness鈥攖he so-called eccentric boffin syndrome) the
official estimate has risen to nearer 1 in 1000. In the 1990s, some health
experts have questioned even these figures, saying there has been a further
unexplained surge in cases where the disorder comes on very suddenly at the age
of two or three rather than being present from birth.
The reasons for some of the strange behaviours of autistics became clearer
when psychiatrists started listening to how patients with mild forms of the
condition鈥攅specially the few who have improved after suffering severe
autism鈥攄escribe their experience. The patients talk about how their minds
fail to pull the world together in a coherent way. Sensory information gets
through, but it is fragmented, meaningless, unpredictable and often very scary
because of this. The withdrawal, the uncomprehending tantrums, the fascination
for simple or repetitive stimuli all follow from not being able to make sense of
the world. One sufferer said she could not see faces, just collections of noses,
eyes and mouths. Words were just strange noises. She found people, with their
looming presence and unpredictable movements, too threatening and so lost
herself in safer activities such as watching motes of dust floating in the
air.
The obvious explanation for the inability to process sensory information is
that something is happening to the infant brain to halt some aspects of its
development. Babies are born with largely unwired brains and have to learn how
to build a world of sensations. During their first few years, they discover that
assemblages of edges and shadows make up common objects like cats and tables.
They develop a lot of the skills necessary to take in the world efficiently,
such as how to shift the eyes from one point of interest to the next.
Brain food
This stable sensory environment then becomes a platform on which to build
more intellectual skills such as speech, play and normal social behaviour.
Autism could be the result of the infant brain being prevented from establishing
basic sensory habits. Certainly, clinical studies confirm that autistic children
are poor at fundamental skills like shifting their attention or focusing their
eyes.
The question then becomes one of what causes the impairment. Few autism
researchers doubt that genes play a role because families often have a history
of developmental syndromes and twin studies show the disorder is often shared.
But there are reasons to think the story is more complicated than that.
Back in 1980s, parents and doctors who ran self-help groups began to pay
attention to some of the more peripheral symptoms of autism such as diarrhoea,
an inflammation of the lining of the small intestine called celiac disease, and
other digestive problems and food sensitivities. Anecdotally, at least,
changing the children鈥檚 diet, by cutting out gluten and casein, or adding
enzymes, vitamins and minerals, seemed to help with both the stomach upsets and
the child鈥檚 mental state.
Two broad hypotheses emerged among those who suspected the disease might have
an environmental trigger. One camp believed autism might be an autoimmune
disease. An allergic reaction, perhaps to something 鈥渂rain-like鈥� in the diet,
might confuse the immune system into attacking the brain itself. Over the past
few years, some support for this idea has come from researchers like Vijendra
Singh of the University of Michigan in Ann Arbor who have found evidence of
heightened immune activity in autistic children. In particular, Singh has
reported an allergic response to myelin protein, one of the building blocks of
the nervous system.
Leaky guts
The second more controversial suggestion was the rogue peptide theory. The
idea was first mooted as long ago as the 1970s, almost as soon as it was
discovered that the brain had receptors for opioids, morphine-like peptide
molecules that it used as a natural painkiller. In fact, the brain uses dozens
if not hundreds of different peptides to control everything from the immune
system to sexual behaviour. Those peptides also play a special role in
development. For example, they switch on a neuron鈥檚 sensitivity to other
neurotransmitters as it reaches its proper position within the brain鈥檚 tangled
pathways.
At the same time, some researchers studying schizophrenia suggested that
disease might be caused by a dietary substance such as the gluten in wheat
leaking through the gut wall, eventually reaching the brain. Shattock and a few
others, notably Kalle Reichelt of the Pediatric Research Institute in Oslo,
Norway, began to suspect that diet-derived peptides could also be to blame for
autism.
As a biochemist, Shattock was well placed to do the tests needed. By 1990, he
and Reichelt had discovered that 90 per cent of the autistic children they
studied had abnormally high urine levels of certain peptides. Most of those
peptides have yet to be positively identified, but one breakdown product of
cow鈥檚 milk, bovine beta-casomorphine, is up to ten times the normal level in
some of the children.
What ever might cause the child鈥檚 gut to leak in the first place remains
unclear, although there are plenty of candidates. One contender is yeast. Yeast
taking root in the gut lining after, say, a heavy course of antibiotics can
create holes. Stomach operations or brain infections, such as encephalitis,
could also erode the gut or the barriers that protect the brain.
The most recent scare has been over vaccines. In February, Andrew Wakefield
of the Royal Free Hospital in London suggested MMR (measles, mumps and rubella)
jabs may trigger inflammatory bowel disease鈥攈inting at another way
peptides could flood a child鈥檚 system鈥攁nd autism (see The Lancet,
vol 351, p 637). The controversy still rages.
Now Shattock has stumbled on another possible mechanism. According to his
studies, the levels of indoleacrylic acid鈥攐r rather, its detoxified
product鈥攁re higher in the urine of autistic children. Very little is known
about the acid except that it is a byproduct of the pathway that transforms the
amino acid tryptophan into hormones and neurotransmitters like serotonin.
There are any number of possible reasons why autistic children may make more
indoleacrylic acid, says Shattock. It could be a genetic defect or an
environmental insult or both. Organophosphates used in fertilisers and
pesticides, points out Shattock, are already known to interfere with other
enzymes similar to those in the tryptophan metabolic pathway. What鈥檚 more, the
chemical structure of the acid suggests it could damage the body鈥檚 barriers by
inserting itself among the fatty components of cell membranes, says
Shattock.
But, he concedes, 鈥渨e might be utterly wrong. The excess indoleacrylic acid
could be due to something else entirely, such as bacterial action in a gut that
was already not functioning normally. It could be a correlation, not a cause.鈥�
Either way, the most important thing is not to fall into the old trap of looking
for a single peg on which to hang the blame for autism, says Shattock.
Miracle cure
In that respect, there has been a softening of attitudes towards the
鈥渃rackpot鈥� idea that through a convoluted sequence of events, dietary peptides
might cause autism. After all, the conventional wisdom had been that the gene
hunters would turn up one or two malfunctioning genes, leading to a single
obvious cause鈥攕ay, a defect in the brain鈥檚 wiring. The fact that they have
fingered so many potential genes linked to autism, makes it more likely that
myriad different mechanisms could make a child susceptible, including, perhaps,
a weak gut.
鈥淭he peptide work was not taken seriously a few years ago, but it is now
looking much more respectable,鈥� says Bristol-Powers. 鈥淲e have to beware of
raising the hopes of parents with promises of miracle cures. But equally, we
need to be careful about dismissing them out of hand.鈥�
Rantala is even more pragmatic: 鈥淭here are so many questions about this
still. But when it is your child, you have to do something. The diet seems to
have worked with Samu and that鈥檚 what matters.鈥�
For his part, by the time Shattock had started to believe that there really
was something in the rogue peptide hypothesis, his son, now a young adult living
in a sheltered community, was too old to benefit. Not that that stops Shattock鈥檚
pursuing the theory. After all, he says, 鈥淚f I鈥檓 right, then it鈥檚 game, set and
match to me and Robert Redford can play me in the film.鈥�