Mad Cows, Sane Cats: Making Sense of the `Species Barrier' NYT 6/3/03

[Guest guest]

New York Times

 

Mad Cows, Sane Cats: Making Sense of the `Species Barrier'

 

June 3, 2003

By SANDRA BLAKESLEE

 

 

 

When thousands of cattle started collapsing from mad cow

disease more than a decade ago in Britain, experts stated

firmly that people would never get the disease from eating

beef.

 

 

A species barrier - a kind of biological Hadrian's wall -

would protect roast beef lovers from harm.

 

 

So much for scientific hubris. After young people began

dying in 1996 from a new variant of Creutzfeldt-Jakob

disease, a rare malady thought to occur only in older

people, the experts were forced to admit they were wrong.

 

 

The people had died because they ate meat from infected

cows. A species barrier had crumbled.

 

 

Unlike SARS, a disease that first appeared in Chinese

vendors who prepared wild animals infected with an exotic

virus, mad cow disease is caused by an even more mysterious

infectious agent, a misfolded protein called a prion.

 

 

When animals eat the remains of their own species or other

species, infectious prions sometimes pass among them.

 

 

Prions can incubate for very long periods of time before

they result in full-blown disease, with each animal or

person experiencing the effects differently. But questions

about which animal can infect which other animal in the

animal world, including humans, continue to perplex

researchers worldwide.

 

 

Can sheep infect cows? Can cows infect sheep? What about

goats and pigs? Or chickens? Can deer infect cattle living

in the same pasture without cannibalism going on? Can deer

infect people?

 

 

Are some animals silent carriers of the disease, giving

meat lovers of the world a false sense of security?

 

 

Answers matter because regulations in United States

intended to keep mad cow disease out of the country and to

control related prion disorders like chronic wasting

disease in deer and elk are based on fully understanding

the biology of species barriers.

 

 

Ranchers, for example, are not allowed to feed their cows

the rendered remains of other cows and closely related

species.

 

 

But such remains can be fed to more distant species like

pigs, chicken and fish. Wastes from those animals, once

rendered, can be fed back to cows.

 

 

In the wake of mad cow disease, this practice of

cross-species feeding is banned in Britain and many

European countries.

 

 

But because mad cow disease had not shown up in North

America until last week, when a cow in Alberta, Canada, was

found to have been infected, regulators here say that cross

contamination is an unlikely threat.

 

 

For the same reason, relatively few American cattle,

compared with those in Europe, are tested for the disease;

if it is rare or nonexistent, it will not have

opportunities to cross species barriers.

 

 

Research on species barriers and prion diseases is fraught

with enigmas, dead-ends, contradictions and confusion.

 

 

Species barriers are very hard to predict, said Dr. Patrick

Bosque, a neurologist at Denver Health Hospital and the

University of Colorado Health Sciences Center who studies

the problem. Often there is no plausible explanation for

why an infectious agent does or doesn't move from one

species to another.

 

 

"We don't understand what's happening," said Dr. Stanley

Prusiner, a neurology professor at the University of

California at San Francisco who won a Nobel Prize for

elucidating prions' disease-causing powers. "Anyone who

believes we understand what's happening is mistaken."

 

 

This much is known. Cells have a huge machinery for folding

up proteins, molecules that carry out most of the body's

work. Each protein can follow many possible folding

pathways to assume its final shape and function. Mistakes

are common, but normally misfolded proteins are routinely

chopped up and recycled or dumped.

 

 

When the normal prion protein misfolds, it resists

recycling and forms a hardy gunk. Some aspect of this

process produces lethal spongelike holes in brain cells.

When an animal is exposed to infected brain tissue, its own

prions can be hijacked and forced to produce more of this

infectious gunk.

 

 

Misfolded prions occur in strains. Each has slightly

different biological properties, including shape,

incubation time, infectious dose, target tissue and

clinical signs of disease. Strains appear to evolve as

species trade prions.

 

 

To learn more about disease transmission, researchers carry

out four kinds of experiments. The slowest, most expensive

ones involve raising animals in shared pens.

 

 

At the University of Wyoming, Dr. Elizabeth Williams, a

professor of veterinary medicine, watches over a group of

cattle of different breeds living with deer and elk

infected with chronic wasting disease to see if the disease

is spread by shared range land.

 

 

But after six years the cows show no signs of illness, Dr.

Williams said, and another group of cows that were fed

rations infected with bits of brain tissue from infected

deer also remain healthy. The experiment is to last 10

years.

 

 

To speed things up, a second approach involves injecting

tainted brain material directly into the brains of various

species.

 

 

Scientists using this technique have created a veritable

Noah's Ark of findings.

 

 

For example, cows injected with scrapie, a sheep prion

disease, get scrapie.

 

 

Sheep injected with mad cow disease develop brain lesions

that look just like scrapie.

 

 

The cow disease can also be passed into pigs and cats, and

to ungulates via injection.

 

 

Cows receiving infected deer tissue develop abnormal prions

but their brains look healthy.

 

 

Sheep that get deer tissue get a disease that looks again

like scrapie.

 

 

Raccoons develop prion disease when exposed to mink or

sheep prions but not deer prions.

 

 

And when elk are injected with sheep scrapie, they develop

a disease that looks identical to chronic wasting disease

in elk.

 

 

Because this kind of injection process would not occur in

the wild, it is not clear what its relevance might be.

 

 

Experts say that resistance to injected prions may be

related to the fact that some animals rapidly clear

misfolded prions, dumping them before they become toxic.

 

 

Because it may take many years for prion diseases to

develop, some species may not live long enough to develop

clinical symptoms.

 

 

A third approach, which is especially good for studying

strain evolution, involves transgenic mice. Rodents that

carry human, cow, sheep or deer prions instead of the mouse

variety are injected with alien prions to see what happens.

 

 

 

Their brains are injected back into other animals to see

what happens.

 

 

The results are often confusing, Dr. Bosque said. Mice with

human prion genes get chronic wasting disease but not mad

cow disease, while humans get mad cow disease but not

chronic wasting disease, so far.

 

 

Some humanized mice infected with bovine disease go on to

develop new variant Creutzfeldt-Jakob disease while others

get a type that looks like sporadic Creutzfeldt-Jakob

disease, the disease of older people that is not related to

cows.

 

 

The fourth strategy is to study prions in test tubes to see

how prions convert one another.

 

 

Chronic wasting disease prions weakly convert sheep,

cattle, human and elk prions to infectious states.

 

 

Whether this is a meaningful surrogate for naturally

occurring disease is not known.

 

 

Finally, an experiment created to study a strong species

barrier recently stunned those in the field. At the Rocky

Mountain Laboratory, a branch of the National Institutes of

Health in Hamilton, Mont., Dr. Richard Race injected

infectious hamster prions into mice known for their

resistance to hamster disease. Most never got sick.

 

 

"We thought that would be the end of it," Dr. Race said.

 

 

 

But when the mice reached old age, he removed bits of their

brains and inoculated additional mice and hamsters.

Hamsters got sick very quickly.

 

 

A few mice in the second generation got sick and by the

time third and fourth generations of mice were inoculated,

the prion strain was lethal.

 

 

Dr. Race concluded that some animals were subclinical

carriers of prion disease, especially for new and varied

strains.

 

 

Concerns about subclinical infection are why people who

lived in Britain during the peak of the mad cow epidemic

are not allowed to donate blood.

 

 

Disease in a new host may not mimic the exact

characteristics of the disease in its original host, he

said. The experiment is worrisome, said Dr. Michael Scott,

a prion expert in Dublin.

 

 

"We could have a situation where an intermediate species,

say a pig, could harbor a subclinical infection of a prion

disease from, say, a sheep which would be pathogenic in

humans," Dr. Scott said.

 

 

http://www.nytimes.com/2003/06/03/science/03SPEC.html?ex=1055647472&ei=1&en=82d

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