All in the mind?
New Scientist vol 176 issue 2366 - 26 October 2002, page 41
Suspicion is growing that one of the most common human parasites in the
world is messing with our minds. James Randerson reports
HAVE you been acting out of character lately? Are you having trouble
concentrating? Don't blame late nights or old age - you might be at the
mercy of a mind-altering parasite. A microscopic beast lying low in your
brain may be exercising a subtle form of thought control, turning you into
somebody slightly different.
This might sound pretty far-fetched, but evidence is growing that
Toxoplasma
gondii - a relative of the malaria parasite - can change the way you
think.
And you might already be infected without knowing it.
Why haven't you heard any of this before? Because medical opinion insists
that Toxoplasma is nearly always harmless, a cause for concern only to
pregnant women and people with a weakened immune system. The case for the
mind-control hypothesis is far from proven. But if it's true, the parasite
will become a public health nightmare overnight.
Toxoplasma - or toxo as it is informally known - is one of the most common
human parasites in the world, infecting between 30 and 60 per cent of the
global population. Any mammal can be infected, but it's only in cats that
toxo can sexually reproduce. It releases eggs that are spread in cat
faeces,
and if these end up in moist soil they can remain infective for 18 months.
A
passing rat or mouse might pick up the infection from the contaminated
soil
and if a cat kills and eats them the life cycle continues.
Toxo's danger to pregnant women comes from the parasite's ability to cross
the placenta and trigger a miscarriage or damage the baby's brain. But
such
cases are fairly rare, with only a handful a year in Britain and similar
levels in other developed countries such as the US and Australia. So apart
from warning prospective mothers against emptying the cat's litter tray,
dealing with toxo has never been a public health priority.
Risk factors vary between countries; most people get toxo from eating
undercooked meat - pigs, cattle and sheep can all carry the parasite. You
can also catch toxo by accidentally ingesting soil traces contaminated
with
cat faeces. So always wash your hands after doing the gardening.
In the initial phase of infection, called acute toxoplasmosis, the
parasite
is present in the blood. Typically, it causes little more than a headache
and sore throat, although in rare cases it can lead to serious eye damage.
Even if you do visit the doctor, it is almost always dismissed as a viral
infection.
After this initial assault, the parasite hides from the immune system by
forming resistant cysts on muscle and nerve tissue, including the brain -
a
stage known as latent toxoplasmosis. For most people, this disappearing
act
is the end of the story. Once the parasite has gone to ground it almost
never re-emerges, unless your immune system is suppressed, if you get
AIDS,
for example. You keep the latent infection for the rest of your life -
there
are no drugs to cure it - but the received medical wisdom is that it is
harmless.
So why the cause for concern? Well, researchers already know that toxo can
manipulate rodents, its natural "intermediate host". Remarkably, rats and
mice behave more recklessly when they are infected (see "Fatal
attraction").
Joanne Webster and her team at Oxford University have found that the
hapless
rodents are more active and less scared of new things. They are even
attracted to cat urine. And research by Jaroslav Flegr and colleagues at
Charles University in Prague has shown that rats have slowed reaction
times.
All this makes them much more vulnerable to a feline pounce, which is
exactly what the parasite wants. After all, toxo needs to infect a cat
(the
"definitive host") to complete its life cycle and spread its genes.
So could humans be subject to the same parasitic puppeteering? True, toxo
would have little evolutionary incentive to influence our actions, as
prehistoric humans were probably not eaten by big cats often enough to
make
it pay off. But rat and human brains are very similar. They have many of
the
same bits and are run by the same collection of chemicals. No one really
knows how toxo subverts rat behaviour but it's likely that it interacts
with
a chemical in the brain. The chances are that the same substance is in our
brains too, so it's perfectly feasible that humans experience side
effects.
Flegr and his team decided to find out if this were actually happening.
They
carried out a series of tests on volunteers, some of whom had a latent
infection, as revealed by antibodies to toxo in their blood.
The results from personality tests were complicated and showed confusing
gender differences, but men at least seemed to mimic one aspect of rat
manipulation. Infected men tended to be more independent and inclined to
break rules, although infected women tended to go the other way. Could it
be
that males are being made more reckless, like the rats, while for some
reason the mind-control chemical has the opposite effect in females? At
this
stage it's still unclear, and of course, there's not necessarily a causal
relationship - certain personalities could simply be more prone to picking
up infections.
But one test, measuring reaction times and attention span, gave more
consistent results (Parasitology, vol 122, p 515). Both men and women who
had a latent infection took longer to press a computer key after a prompt
from the monitor. People without an infection took about 250 milliseconds
to
react, but those with a latent infection reacted about 8 per cent slower.
What's more, toxo-positive subjects did worse as the experiment went on,
suggesting that they have shorter attention spans. Again, the effects in
humans seem to be mimicking those in rats.
Until recently, few people have taken Flegr's results very seriously. So
what if toxo causes a few strange lab results, what difference does that
make in the real world? What made people sit up and take notice was
research
published in August by Flegr's team showing that humans with a latent
infection are 2.7 times more likely to be involved in a car accident (BMC
Infectious Diseases, www.biomedcentral.com/1471-2334/2/11).
Dangerous driving
The researchers tested blood samples from 146 people involved in car
crashes
for which they were at least partly responsible, and 446 control subjects.
There were more toxo carriers in the "accident" group. It didn't matter
whether the subject was a driver or a pedestrian, having the parasite
makes
you more of a danger to other road users. Worryingly, there's an obvious
link with Flegr's reaction time results. And if toxo slows our reaction
times, what other effects is it having? Could it contribute to other
transport accidents or industrial mishaps?
Flegr's study has certainly raised eyebrows among the small group of
specialists in the field, including some public health officials. For
example, Richard Holliman, a parasite researcher at St George's Hospital
Medical School in London, says that although the results need to be
replicated: "The implications could be huge."
Longer reaction times might not be the only neurological effect of toxo.
Another controversial idea is that latent infection might trigger some
forms
of schizophrenia. Fuller Torrey at the Stanley Medical Research Institute
in
Maryland and his team has found that schizophrenics are more likely to be
cat owners, and to have latent toxoplasmosis. What's more, drugs used to
relieve schizophrenia symptoms happen to harm the parasite, at least in
the
test-tube. Torrey believes this may be why the drugs work.
So what should we do if it turns out that significant fractions of the
population are infected with a parasite that slows reactions and possibly
causes serious mental health problems?
Holliman, for one, says that we would have to consider which professions
we
allow infected people to enter. Would we want someone with slowed
reactions
working as an airline pilot, for example, or driving a lorry? On the other
hand, if we banned all infected people from jobs where fast reactions are
important, we could lose a third of our workforce or more.
In any event, toxo is unlikely to be a problem for airline pilots. The
licensing process usually involves rigorous aptitude testing, which is
designed to weed out anyone with chronic impairments. Tony Evans, deputy
chief medical officer at the UK Civil Aviation Authority says: "If you're
performing below par, you're not going to get through the course."
But what about all the other professions where reaction times matter? If
it
turns out that latent toxoplasmosis really slows you down should bus
drivers
or machinery operators be screened for the parasite? And if insurance
companies decide that toxo-positive drivers are a greater risk, will they
be
justified in charging them higher premiums?
Cutting the number of people who become infected with toxo in the first
place is clearly an important way forward. Unfortunately, the only animal
species for which a vaccine is available is sheep, because acute infection
has serious consequences for farmers. So-called "abortion storms", when up
to 50 per cent of ewes in a flock miscarry, occur because they're exposed
to
the parasite.
But progress towards a human vaccine has been frustratingly slow.
Researchers have identified components of the parasite that provide some
protection against infection when injected into mice. But this early work
has stalled through lack of funding. There is not much interest in the
area
because, although toxo is an important parasite, it doesn't kill, says
Fausto Araujo at the Palo Alto Medical Foundation in California who was
involved in the mice studies. Perhaps if the Czech findings are
substantiated, vaccine research will acquire a new urgency. In the
meantime,
the only option seems to be reducing the parasite's spread through basic
public health measures.
Many people pick up toxo from undercooked meat, so better kitchen hygiene
and thorough cooking should go a long way to lowering infection rates. In
a
recent survey, Tanya Aspinall and colleagues at the University of
Manchester
Institute of Science and Technology found that 27 of 71 meat products from
British supermarkets harboured toxo DNA, although they don't know if the
parasites were viable.
Holliman is adamant that tackling the parasite in meat is the best option
for reducing human infection. "There's no good reason why food should be
sold with viable Toxoplasma in it," he says. On that score, keeping cat
faeces away from animal feed is fundamental.
In Britain, attitudes to the toxo public health threat vary from concern
to
indifference, often depending on how well informed the speaker is. A
spokesman for the British government's Department for Environment, Food
and
Rural Affairs said officials were unaware of the studies on human
behaviour.
But the government-funded Toxoplasma Reference Laboratory in Swansea has
been monitoring this research. Clinical scientist Edward Guy says the
findings aren't yet strong enough to justify action, and he is keen to
avoid
public panic of the sort that surrounded unsubstantiated research linking
the MMR vaccine to autism.
Down on the farm
The issue has also been discussed by the government's Advisory Committee
on
Zoonoses, which reviews the dangers posed by animal diseases that can be
passed to humans. It is already considering what new policies would be
needed if toxo turns out to be more dangerous than we think, or if the
public becomes more concerned about it. One option is tighter controls on
farms to prevent animals picking up the parasite.
The public health implications of toxo seem to be a higher priority in
America. The US Department of Agriculture has recently commissioned a
three-year study of beef, chicken and pork going into the food chain to
assess the risk to the consumer. The researchers will analyse 6000 meat
samples. "The study will provide the first risk assessment of the
likelihood
of exposure to Toxoplasma by ingesting raw or undercooked meat," a
department spokesman says.
Pigs have traditionally been thought of as the most likely animals to pick
up a toxo infection so the USDA is being advised by Elizabeth Wagstrom,
director of veterinary science at the US National Pork Board, which
represents producers. She says that US pork infection levels are falling
because of more intensive, indoor farming, which keeps pigs away from
cats.
But such gains could be reversed if organic farming becomes more common.
"It's a lot more difficult to control the parasitic disease with animals
outside," says Wagstrom.
Ultimately we'll have to wait and see if the latest findings are backed up
by more research. No one is suggesting drastic policy changes on the back
of
a handful of studies. But toxo researchers complain that the field is
being
held back by dogma. It's hard to get funding because of the entrenched
belief that latent toxoplasmosis is harmless. Holliman says that
alternative
theories are seen as "too off-the-wall".
Yet no one can give a good scientific reason why these effects couldn't
occur. After all, toxo profoundly changes rodent behaviour, so why not us
as
well? As Joanna Webster says: "I definitely think there is something
there.
There's no reason to think that the parasite could not manipulate humans."
Fatal attraction
If you're a rat, and you like being alive, it goes without saying that you
don't go near cats. So it's not surprising that most rodents do a very
effective vanishing trick at the faintest feline whiff. But not rats
infected with the parasite Toxoplasma gondii. In toxo-rats, the parasite
is
calling the shots.
Mice and rats pick up toxo from food that's been in contact with
contaminated soil. But winding up in a rat is a dead end for the
microscopic
parasite because it can only complete its sexual cycle in a cat's guts.
Joanne Webster and her team at Oxford University have found that toxo has
some tricks up its sleeve. Toxo somehow changes its host's behaviour,
making
it more likely to finish up in a cat's stomach.
Webster's team trapped wild rats - some of which were naturally infected
with toxo - and videoed their nocturnal movements in outdoor cages. The
infected animals were more active than the others and also more willing to
approach food masked with a novel smell. Both changes are hard to put down
simply to the rats being weakened by the infection, says Webster.
But the real clincher came when the researchers offered the rats a choice
of
bedding - their own, or bedding laced with water, cat urine or rabbit
urine.
Cat urine, is usually a big turn-off for rats, but the toxo-rats actually
preferred it.
Toxo can infect every species of mammal. So can we be confident that the
rodents are the only ones with a death wish? Although our brains are much
bigger, they are fundamentally very similar to a rat's. So if the
micro-manipulators are pulling the strings there, why not in us as well?
James Randerson
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