http://www.stanleylab.org/Document/cat%20press%20release.htm

Linguafranca - Volume 10, No. 9, December2000/January 2001

Pet Theory

Do Cats Cause Schizophrenia?
by Stephen Mihm

"I think cats are great," say E. Fuller Torrey.  His office decor
would seem to confirm this statement: A cat poster hangs on one wall;
a cat calendar sits on his desk; and a framed picture of a friend's
cats leans against the windowsill.  He even admits to having a "cat
library" at home.

But Torrey's interest in felines is a bit different from that of your
typical cat lover.  That's because Torrey, a psychiatry professor at
the Uniformed Services University of Health Science and the enfant
terrible of mental health research, believes that Felis domestica may
carry infectious diseases that could cause schizophrenia and bipolar
disorder.  "My wife thinks I'm going to be assassinated by cat
owners," says Torrey with a sigh.  "In fact, I like cats.
Unfortunately, if we are correct that they transmit infections..."
Here his voice trails off, and he pensively fingers his closely
cropped beard.

Torrey often speaks in a self-deprecating manner of his "delusional"
notions, but he's dead serious about the cat connection.  He thinks
"typhoid tabbies" are passing along Toxoplasma gondii, a parasite that
causes brain lesions and, if Torrey is right, schizophrenia.

Torrey first made the argument nearly thirty years ago.  "It was
considered psychotic," he admits.  But since then, his ideas, though
still outside the mainstream, have attracted converts, most notably
the Johns Hopkins virologist Robert Yolken, with whom he now
collaborates.  Together, they're trying to prove that toxoplasmosis is
but one of several infectious diseases that causes most cases of
schizophrenia and bipolar disorder.  It helps their case that previous
explanations--bad mothering, bad genes--have proven deficient to
varying degrees.  But Torrey and Yolken have also uncovered some hard
evidence to support their claims, and they are about to put their
theory to the test with clinical trials of drugs that are new to the
psychopharmacological arsenal: antibiotics and antivirals similar to
those used by AIDS patients.  If the duo finds that such drugs alter
the course of schizophrenia, Yolken observes, their results "would
represent a major advance in the treatment of this devastating disease
as well as in understanding its basic etiology."

"Schizophrenia is a cruel disease," Torrey has written, with
considerable understatement.  Although it affects only 1 percent of
the population, schizophrenia is among the most debilitating forms of
mental illness.  Trapped in a world of private delusions, a
schizophrenic might cling, for example, to the belief that he is Jesus
Christ, or that the government has implanted a monitoring device in
his mouth during a routine dental procedure.  Visual and auditory
hallucinations can range from the terrifying to the merely strange:
gigantic spiders, voices that insult or instruct.  Some schizophrenics
withdraw, becoming mute or catatonic; others remain communicative but
incoherent, jumping from one topic to another without logical
connections.

With little or no warning, schizophrenia usually manifests itself in
patients between the ages of sixteen and thirty.  From then on, the
illness waxes and wanes, with symptoms generally becoming less severe
as the patient ages.  Psychotherapy is of little help to
schizophrenics, but medication and constant medical care enable over
50 percent to make a full recovery.  Still, relapses are common, and
many patients spend their lives in halfway houses and institutions.
Approximately 40 percent of schizophrenics don't get the help they
need and end up on the streets or in prisons--or committing suicide.

There has never been a consensus on schizophrenia's etiology or cause.
Many nineteenth-century psychiatrists thought it was a biological
disorder; some speculated that it might have an infectious origin.  As
far back as 1845, the French neurologist Jean E. Esquirol wrote that
"mental alienation is epidemic."  He added: "It is certain that there
are years when...insanity seems suddenly to extend to a great number
of individuals." In 1974, the American Journal of Insanity published a
lengthy brief titled "On the Germ-Theory of Disease." By the early
twentieth century, doctors like Eugen Bleuler had suggested that "the
connection of [schizophrenia] to infectious process equally needs
further study." An outbreak of psychoses after the 1918 influenza
epidemic and the discovery that syphillis could cause dementia lent
further credence to such theories.  In 1922, the psychiatrist Karl
Menninger hypothesized that schizophrenia was "in most instances" the
by-product of viral encephalitis.

Menninger later became a prominent Freudian psychoanalyst, following a
career trajectory that mirrored a larger movement in American
psychiatry away from biological explanations of mental illness.  By
the 1950s, Freudian thought had solidified its grip on the American
psychiatric profession.  That also happened to be the time when Torrey
first began thinking of a career in psychiatry.

As he tells it, the formative event for him came between his second
and third years at Princeton.  His sister, who was due to start
college that fall, began hallucinating and yelling, "The British are
coming!"  The diagnosis was acute schizophrenia. "My mother was told
that it was because my father had died," Torrey says with disgust. "I
thought, 'This is absurd--a lot of people's fathers die and they don't
develop schizophrenia' There was this disconnect between what I was
looking at and what I was being told."

As Torrey wrapped up his degree at Princeton and went on to a medical
school at McGill, he began seriously to contemplate a career in
psychiatry.  After two years as a Peace Corps doctor in Ethiopia and a
year in the South Bronx helping to set up one of the area's first
neighborhood health centers, Torrey began a psychiatry residency in
Stamford, Connecticut.  "It looked to me as if psychiatry was at least
twenty years behind the rest of medicine," he recalls.  "It was more
likely to move and be exciting during my practicing lifetime."

That wasn't what attracted most people to the field in the 1960s.
Says Torrey, "Psychiatry was the thing you could do if you found
yourself in medical school and realized that you had made a terrible
mistake--that giving people rectal exams was pretty unsavory and not
what you wanted to do.  You could still be paid to be a doctor and
talk to people about their problems." Those problems didn't include
schizophrenia, Torrey remembers: "To specialize in schizophrenia was
about the lowest form of psychiatric practice."

Torrey was undeterred.  Not long after he went to work as a special
assistant to the director of the National Institute of Mental Health
(NIMH), he attracted controversy by publishing a bruising attack on
Freudian psychoanalysis.  In The Death of Psychiatry (Chilton, 1974),
Torrey argued that psychiatry should either limit itself to the
treatment of patients with severe brain disorder--schizophrenia,
bipolar disorders--or abandon its medical pretensions altogether.  In
1976, he moved from NIMH to St. Elizabeth's Hospital in Washington DC,
where he achieved considerable renown as an advocate for the seriously
mentally ill. He also helped found the National Alliance for the
Mentally Ill, a nationwide patient advocacy group.

The turning point in Torrey's career came in 1983, when he published
two books: Surviving Schizophrenia, which soon became an authoritative
text for patients and families; and The Root of Treason, a biography
of Ezra Pound based on research conducted at St. Elizabeth's.  The
second book, which was nominated for an award by the National Book
Critics Circle, was inspired by rumors that Pound had sought refuge at
St. Elizabeth's after World War II to avoid standing trial for
treason.  When Torrey researched the case, he discovered that a
hospital administrator had colluded to protect Pound by declaring him
insane.  It was a great piece of detective work, but the book earned
Torrey a demotion at St. Elizabeth's.  Disillusioned, he retired two
years later and began pursuing his unorthodox theories of
schizophrenia.  That meant getting inside the brain of the
schizophrenic--literally.

"The brain is in a very inconvenient place," says Torrey, guiding me
up the walkway to a boxy white building on the grounds of the Naval
Hospital in Bethesda, Maryland.  "People just don't like you opening
their heads and looking around while they're alive."  This building,
he tells me, houses a solution to that problem.  He opens a door and
we enter what looks and smalls like the maintenance area of an indoor
pool. "The Navy has a dive chamber here," says Torrey, pointing to
something that looks like a beached bathysphere in the middle of a
large warehouse. "We're sharing space with them for now."

This is home to the Stanley Foundation Brain Bank and Neuropathology
Consortium's laboratories.  Scattered throughout the building's
corridors and storerooms are some fifty-five freezers containing the
brains of about 285 people--schizophrenics manic depressives, people
with severe depression, and so-called normal controls.  The bank
obtains the brains with the assistance of designated medical examiners
and the permission of surviving family members.  Each brain comes with
a complete set of medical records, family medical histories, and other
clinical information.  The brains are then made available to mental
illness researchers worldwide, including Torrey and his colleagues.
The whole undertaking, along with a number of related projects, is
funded by Theodore and Vada Stanley, wealthy philanthropists who made
their money selling mail-order collectibles.  (In one of his many
roles, Torrey is the executive director of the Stanley Foundation, an
organization that dispensed some twenty-one million dollars in
research funds last year.)

As we wind our way down hallways packed with gigantic freezers, Torrey
stops to turn on the light on what looks like a storage closet.  "Here
are the brains," he says, pointing to countless plastic pails stacked
on metal shelves.  "We put half of each brain in formalin and half in
the freezers." Torrey turns out the light. "Sometimes I take a brain
to show my students.  They always enjoy that."

We enter a room where most of his staff work.  Torrey is in his
element, clapping pathologists on the shoulder, joking with them,
seemingly oblivious (unlike me) to the business at hand; carving up
brains with what looks disturbingly like the meat slicer used at the
local deli.  The staff are equally upbeat, even when describing the
downside of the work.  "It can be a little depressing at times,"
admits Dr. Maree Webster, who runs the bank. "Many of the brains are
from suicides, that sort of thing.  It's really tragic."

The Brain Bank is the culmination of Torrey's dream to study
schizophrenia from the inside out.  He hopes that the collection will
ultimately lead researchers to the cause of he disease.  As for
himself, he's hoping that one day he and his colleagues will find
their hypothetical virus, though, as Webster admits, "it's a little
like trying to find a needle in a haystack.  The brain is a big
place."

And viruses are pretty small.

Torrey dates his obsession with infectious diseases to the early
1970s. "I was becoming aware of proven cases of viral encephalitis
that had been diagnosed as cases of schizophrenia or cases of manic
depressive illness," he recalls.  Torrey discovered some of the cases
in the work of Menninger and others near the turn of the century.  It
was also during the 1970s that the future Nobel Prize winner Daniel
Carleton Gajdusek published some of his first research on so-called
slow viruses--pathogens that lie quiescent for twenty or thirty years
before emerging as full-blown infections.

Intrigued, Torrey met with Gajdusek. In conversation, the elder
scientist mentioned a trip he had made to the highlands of Papua New
Guinea to catalog neurological disorders.  He told Torrey that he had
never found a cut-and-dried case of schizophrenia there, despite the
fact that the disease is supposed to afflict about 1 percent of the
world's population.  Torrey himself made several trips and confirmed
as much. "But on the coast," he recounts, "where there had been
missions and contact with outsiders for a hundred years, you found
occasional cases."  To Torrey, that raised the tantalizing possibility
that some kind of infectious agent was at work.

Torrey' theory started to look even more plausible when he began to
collaborate with Robert Yolken, who now runs the Stanley Division of
Developmental Neurovirology, based at the Johns Hopkins Children
Center.  Yolken, a summa cum laude graduate of Harvard who stayed on
for a medical degree, is a study in contrasts with Torrey.  Whereas
Torrey spins stories and lingers on words for effect, Yolken speaks
without affect at an extraordinary rapid rate, as though his tongue
can barely keep pace with his brain.  Pictures of ski vacations with
his family and Torrey are taped to the shelves above his computer.

When the two scientists began working together in the 1980s, genetic
explanations had usurped traditional psychoanalytic theories about the
causes of schizophrenia.  The new biological paradigm held that it was
only a matter of time before some hypothetical "schizophrenia gene"
would be identified, solving the mystery.  But Torrey and Yolken
remained skeptical.  There were some things that genetics couldn't
explain.  For starters, several studies had shown that children born
in urban areas were more likely to develop schizophrenia than those
born in rural regions.  Household crowding, too, had been demonstrated
to be a risk factor.  And both urban living and household crowding
increase exposure to infectious agents.

Schizophrenia also appeared to correlate with birthdays.  More than
250 epidemiological studies, including some of Torrey's own, have
demonstrated that both schizophrenic and manic depressive patients are
between 5 and 15 percent more likely to have been born in the winter
or spring months.  Part of that statistical bump, in Torrey's opinion,
could be attributed to the increased rate of viral infection in the
colder months.  "The seasonality data make the geneticists very
uncomfortable," says Torrey.

Paul Ewald, a professor of biology at Amherst College and a specialist
in infectious diseases, is a bit more blunt.  "With schizophrenia, you
have seasonal correlations, which is a telltale sign of infectious
agents.  There are not that many things that can explain that
association," he says. "Unless you believe in astrology."

Ewald is little known in mental health circles, but his theories have
already earned him considerable attention among infectious disease
specialists.  He and his collaborator, Gregory Cochran, believe that
many diseases--heart disease, various forms of cancer, multiple
sclerosis, cerebral palsy, most major psychiatric diseases--are often
caused by infectious agents.  Their reasoning is simple: Any gene that
adversely affects an individual's ability to reproduce and care for
offspring will ultimately fall victim to natural selection.
Therefore, severe common diseases--those having an incidence higher
than one in a thousand--can't be chalked up simply to bad genes.  Some
kind of environmental factor, either infectious or noninfectious, must
play a role as well.

Schizophrenia, says Ewald, must be one of these diseases, because it
seriously diminishes a person's reproductive fitness.  At the same
time, neither he nor Torrey and Yolken suggest that genetic factors
are irrelevant.  After all, there's plenty of evidence that genes play
a role in schizophrenia.  One measure of that is the monozygotic twin
test, which yields the percentage of identical twins who both develop
a particular disease.  A concordance rate of 100 percent is evidence
of a purely genetic disease, one that is little influenced by
environmental factors like infection, nutrition, or toxins.
Huntington's disease, for example, has a concordance rate of 100
percent.  Similarly, Down's syndrome has a concordance rate of 95
percent; autism, 82 percent.  By contrast, a viral infection like
polio has a concordance rate of only 36 percent among identical
twins-thus, genetics plays some role, but most of the blame lies with
the polio virus.  What about schizophrenia?  According to Torrey's
(controversial) calculations, the concordance rate averages
approximately 28 percent.  With a rate that low, says Ewald, "we have
to look elsewhere."

For Torrey, Ewald, and others, that means looking for some kind of
infectious agent that may exploit a genetic weakness when invading a
host.  This interplay of genetics and infectious disease is complex
and has a lot to do with whether a faculty gene permits the virus,
bacterium, or parasite in question to lock onto cells.  As Yolken
explains it, these "genetic determinants" are different from those
involved in typical "genetic" diseases like Huntington's in that a
person's genetic susceptibility doesn't surface unless he or she comes
into contact with a particular environmental factor.  In theory,
that's why one identical twin and not the other will come down with
schizophrenia: Only one is exposed to the "schizovirus."

Torrey says that these theories aren't news to most people in the
medical profession, particularly those working with infectious
diseases.  "Psychiatrists," he notes in an exasperated tone, "are the
only ones that are surprised by this."

Torrey is talking about cats again. "I've given talks on the cat stuff
and people's response is almost universal: "I'm not surprised--I've
known my cat is schizophrenic for years!" He chuckles. "One talk I
gave at a department of psychiatry, a fellow came up to me and said,
"I don't want you to repeat this, but the former chairman of our
department of psychiatry was convinced that his cat was hallucinating,
so he gave him liquid Thorazine and it really seemed to help." Torrey
looks at me and smiles. "People find cats strange, so that don't find
this idea so odd."

Yolken, who owns two cats, is less critical of our feline friends, but
he agrees that there may be a connection. "Cat feces are the biggest
source of toxoplasma infections in the United States," he says,
preparing to guide me through a PowerPoint presentation at his desk.
Toxoplasma, Yolken informs me, is one of the more adaptable parasites,
able to set up show in any number of mammals.  Although most humans
can battle, or even carry, toxoplasma without ill effects, the
parasite poses a special danger to people with compromised immune
systems.  It is also hazardous to pregnant mothers and their fetuses,
causing serious brain lesions and retardation in infants when
contracted during the first trimester of pregnancy. That's why doctors
now forbid expectant mothers to clear litter boxes.  Torrey and Yolken
speculate that a toxoplasma infection contacted during pregnancy or
infancy could lie dormant in some patient's central nervous system,
only to be reactivated when the host's immune system is compromised by
a secondary infection in late adolescence.

Cats, meanwhile, don't seem to suffer toxoplasma's ill effects.  They
pick up the parasite from eating infected rodents, typically rats or
mice.  In the rodents themselves, the parasite produces brain lesions
and a host of rather odd behaviors.  Infected rats, for example, lose
their instinctive fear of cat urine, making them more likely to be
caught and eaten by feline predators.  As Ewald explains, "The
parasite gets to the next host in its life cycle by messing up the
rodents' minds," Once in the cat, the parasites infect the lining of
the small intestine, reproduce asexually, and encase themselves in a
sturdy membrane.  These oocysts, or spores, are then shed in the cat's
feces.  The cycle begins anew when human beings and other mammals
become infected from handling the feces, or in some cases, breathing
and swallowing the airborne spores.

Torrey first postulated that toxoplasma might cause schizophrenia in
the 1970s, when he read several articles attributing an outbreak of
multiple sclerosis in the Faeroe Islands to the introduction of dogs
there during World War II.  Could indoor pets like cats, which had
become widely popular only in the nineteenth century, also be
reservoirs of infectious agents? Torrey, who had recently completed a
book manuscript arguing that in the late nineteenth century
schizophrenia and bipolar disorder went from being rare diseases to
relatively common ones, became convinced that cats were central to
that story. "The cat craze began with the cat shows in the late
nineteenth century," he explains. "And when I went back and looked at
what we know about cats as pets, it corresponded almost perfectly to
what we know about the rise of psychosis.

Eager to test the theory, he and Yolken conducted a study in the early
1990s wherein patients of schizophrenics and nonschizophrenics were
asked whether they owned a cat during pregnancy or when their
offspring were young.  That study revealed a higher incidence of cat
ownership among the parents of children who developed schizophrenia
(51 percent) versus those who did not (38 percent).  A second study,
much larger in scope, looked into nineteen different factors,
including cat ownership, dog ownership, complications during
pregnancy, breast feeding, and urban versus rural residence.  Only
five of the variables proved statistically significant, cat ownership
among them (52 percent of those who developed had lived with cats
versus 42 percent of the nonschizophrenics).  Dog ownership, by
contrast, was marginally more common among nonschizophrenics (78
percent) than among schizophrenics (73 percent).

Such epidemiological data are further supported by a recent study by
Yolken and Stephen Buka of the Harvard School of Public Health.  The
two stumbled onto medical records and blood samples taken from some
fifty-five thousand pregnant women taken between 1959 and 1966 as part
of a study on the causes of cerebral palsy.  Buka tracked down about
twenty-five hundred families from Providence, Rhode Island, who took
part in the study.  Among these families, twenty-seven children had
exhibited psychoses.  Buka matched these with some fifty-four controls
of the same age, sex, race, and month and year of birth.  Yolken then
subjected the blood samples of both groups to a battery of tests for
different antibodies.  The mothers of the children who later developed
psychoses were approximately 4.5 times more likely to have antibodies
to toxoplasmosis than the mothers of the healthy controls.

"It's been known for a long time that toxo can get into the brain,"
says Yolken. But can it cause schizophrenia? One bit of evidence, he
says, comes from the AIDS epidemic. "It turns out," he explains, "that
about 30 percent of the adult population is toxo-positive"--that is,
has antibodies to toxoplasmosis--" and that if you suppress our immune
systems enough, we'll get toxoplasmosis. Most HIV patients who are
toxo-positive will eventually show signs of toxoplasmosis." Today many
such patients get medication to prevent this, but a decade ago, Yolken
recalls, "we saw massive toxo." He thinks it was probably there all
along, hibernating in the brain.  So far, his and Torrey's attempts to
find evidence of toxoplasma in the brain of schizophrenics have
failed. "The brain is a big place," says Yolken with a sigh. "And it
doesn't take much toxo to start an infection."

Of the other diseases that Yolken tried to correlate with
schizophrenia--rubella, influenza, cytomegalovirus, chlamydia, and
herpes simplex 2 (HSV-2)--only herpes was significant.  Tests showed
that mothers of schizophrenic children were 5.8 times more likely to
have antibodies to HSV-2 than mothers of the healthy controls.

How might a herpes infection contracted in the womb lead to mental
illness years later? As Yolken sees it, the age when most
schizophrenics first develop symptoms suggests exposure to some sort
of "infectious agent which has a higher rate of transmission in late
adolescence and early adulthood." Yolken hypothesizes that the herpes
virus remains quiescent in the brain until adolescence, when it is
triggered by the Epstein-Barr virus that causes mononucleosis, also
known as the kissing disease.  Another theory holds that it is
reactivated by another version of itself picked up in sexual contact.
How such an infection translates into schizophrenia is still a matter
of considerable speculation.  Yolken is wary of saying that herpes
causes schizophrenia. "These represent complex disorders," he says.

Adding to the complexity, Yolken thinks that other kinds of viruses
also play a role in severe mental disorders.  He and Torrey have just
completed a study in which more than 17 percent of patients who
recently manifested schizophrenia had antibodies to the multiple
sclerosis retrovirus. Equally interesting to Yolken is evidence that
in nearly 30 percent of recent-onset schizophrenics, endogenous
retroviruses had made copies of themselves. In both cases, the rate
for the controls was zero percent.

Endogenous retroviruses, admits Yolken, "are not well known in the
scientific community." They are viruses that are incorporated into the
human genome.  In other words, he explains, at some point in
evolutionary history, "progenitors of humans or primates got infected
with a retrovirus, and the retrovirus got into the genome and stayed
in the genome." As a consequence, foreign bits of genetic materials
are scattered through the human genome. "In most cases, they don't
seem to do very much," Yolken says reassuringly.  But it seems that is
some cases they can be activated by other viruses.  Then the little
stowaways begin to make copies of themselves, perhaps wreaking havoc
on adjacent genes and, Yolken conjectures, triggering schizophrenia.

If schizophrenia is caused by a virus, can it be cured? "What we don't
know is whether the infection is reversible," say Yolken.  "If the
damage is done in childhood, then treating patients as adults may not
work." Still, he and Torrey are going to try: They are administering
acyclovir, an antiviral drug better known for its efficacy against
herpes infections, to groups of schizophrenic patients.  They're
encouraged by several previous studies, including one of their own,
which has shown that antipsychotic drugs like Thorazine, Haldol, and
clozapine inhibit viral replication.  Torrey and Yolken hypothesize
that the drugs' efficacy may have something to do with their antiviral
properties.  In a subsequent trial, they will administer antibiotics
customarily used to treat toxoplasmosis.

Although Torrey and Yolken's theory that an infectious disease causes
schizophrenia has gained some acceptance, or at least respect, it is
still far from the prevailing view.  Torrey in particular has many
critics, even among colleagues with whom he has collaborated.

Take Irving Gottesman, a professor of psychology and clinical
pediatrics at the University of Virginia and a major proponent of
genetic explanations of schizophrenia.  The two men maintain a
friendly relationship despite their differences.  "The thing that
keeps us together," explains Gottesman, "is that we have common
enemies: the Freudians, the sociologists, the cultural
anthropologists"--anyone, in other words, who wants to ascribe
schizophrenia to nonbiological causes. They frequently co-author
articles attacking what they perceive to be misallocations of mental
health research  funds.  But when it comes to explaining
schizophrenia, they part ways.

Gottesman casts doubt on Torrey's data for the rate of concordance for
schizophrenia among identical twins.  "He's always trying to lower the
rates," claims Gottesman. "I'm just doing it the way geneticists have
always done." Gottesman's statistical method, known among geneticists
as probandwise concordance, samples admissions to a particular
hospital. If one member of an identical-twin pair shows up with
schizophrenia and the other member shows up at a different hospital
with schizophrenia, too, then the twin pair counts as one concordant
pair.  But if one twin shows up at the hospital and the other twin
shows up at the same hospital, each twin counts as a concordant pair,
thus yielding two pairs instead of one.  This method produces a
concordance rate that's close to 50 percent. "Geneticists use
probandwise to avoid errors when comparing rates with the general
population rate," explains Gottesman.

"I call it a system of double counting," says Torrey of Gottesman's
method.  "I don't know of any other people outside of psychiatry who
use the probandwise concordance rate." Paul Ewald agrees.  In an
e-mail, he notes that "proband concordance is vulnerable to
overestimates on the basis of selection biases...I trust Torrey's
figures for schizophrenia," he writes. "They don't incorporate this
bias."

Nonetheless, Gottesman is certain that genes play a bigger role than
Torrey and his colleagues admit.   In fact, Gottesman has helped
formulate a multiple-gene theory of schizophrenia, which holds that
the disorder arises from a complex set of interactions between many
different genes.  He's also interested in what he calls epigenetics,
the study of environmental factors--drugs and other toxins, for
example--that control or trigger gene events.

"Viruses could be epigenetic contributors, too," concedes Gottesman.
But he will accompany Torrey only so far down that road.  Back in
1994, when Gottesman and Torrey published the findings of a landmark
study of twins and schizophrenia, they offered their differing
interpretations of the results not as a traditional conclusion but in
the form of a fictional conversation among three experts.  Gottesman,
who spoke for the geneticists under the pseudonym Dr. Mendel M.
Malgene, urged Torrey, who assumed the non de plume Dr. Dena S.
Daverus, not to dismiss or diminish the complex interplay of different
genes.  He also pointed out that the brain scans they had conducted in
the course of their study revealed broad, scattered types of changes
in the structure of schizophrenic brains. Infectious diseases like
rabies or polio, by contrast, afflict very specific types of cells or
regions of the brain.  And anyhow, says Gottesman today, "If
schizophrenia is caused by an infectious disease, why is it that
psychiatric nurses and psychiatrists don't have higher rates?  He
pauses. "Why don't spouses of schizophrenics have higher rates of the
disease?"

Joining Dr. Daverus and Dr. Malgene in the fictional schizophrenia
debate was Dr. A. Dominic D'Velupmoni, modeled after Daniel
Weinberger, who in real life represents what has since become the
dominant school of thought about the disease.  Weinberger, who is
chief of the Clinical Brain Disorder Branch Intramural Research
Program at the National Institute of Mental Health, is one of the most
articulate spokesmen for what is known as the neurodevelopmental
hypothesis.  Writes Weinberger, "It has recently become de rigueur to
refer to schizophrenia as a neurodevelopmental disorder in which the
primary cerebral insult or pathological process occurs during brain
development long before the illness is clinically manifest." In other
words, as Weinberger explains it to me, something "disrupts the normal
programs of brain development." That could be a faulty gene or an
obstetric complication. Or something else: Like Gottesman, Weinberger
is willing to consider that viruses might play a role. "Genetics can't
explain it all," he says. "There have to be environmental factors,
too, and viruses may be one of those." But though he describes
Torrey's viral theory as "very provocative, very interesting,"
Weinberger argues that "it's been supported by very little credible
scientific data."

The neurodevelopmental theory "is not a theory about a specific cause:
it's a theory about timing," counters Torrey. "We have fashions in
schizophrenia research, and the neurodevelopmental theory is very
fashionable right not." As he sees it, Weinberger needs to explain
what exactly causes the schizophrenic brain to develop in the way it
does.  Attributing some of that process to obstetric complications or
malnutrition during pregnancy, as some proponents of the
neurodevelopmental hypothesis do, doesn't add up.  Areas of the world
that have the worst prenatal care, diet, and rates of obstetric
complications do not have higher rates of schizophrenia; if anything,
Torrey points out, the incidence of schizophrenia may be lower in such
places.

Neurodevelopmental thinking nonetheless remains at the center of
current psychiatric accounts of schizophrenia.  And though Torrey and
Yolken's views currently sit on the margins, Ewald does not think they
will remain there. "Infectious causation has been seriously
underestimated from the 1800s onward," he notes. "Many people who
suggested infectious causes of diseases were dismissed but later
proven right." Take gastric ulcers. Only in the last decade did
researchers prove that Helicobacter pylori bacteria, not stress and
hot food, cause most ulcers--even though evidence for this has been
accumulating for over a century.  With a disease as complex and
mysterious as schizophrenia, Ewald admonishes, researchers need to be
careful not to reject infectious disease hypotheses out of hand.

To be sure, the field is less divided today than it was when Torrey
began his training some thirty years ago.  Almost everyone in
psychiatry now accepts the biological model of mental illness. No
surprise, than, that Torrey, Yolken, Gottesman, and Weinberger all
admit that their theories may well be compatible.  At the same time,
none shows much willingness to dilute a life's worth of research with
such compromise. "The best theory of all would  be one that integrates
all of them without preconceptions," says Gottesman. "But," he says
sadly, "Who's going to do that?".

STEPHEN MIHM is the producer of The New York Times Magazine on the web
and a doctoral candidate in history at New York University.  He lives
in New York City with this three cats, all of whom declined to be
interviewed for this story.