- The prion is a protein that somehow gets twisted into
a deadly form. Once it does, it's nearly indestructible. It can withstand
temperatures of 1,100 degrees Fahrenheit, and disinfectants are useless
against it. . . . It's the only known infectious agent that has no DNA
or genetic material of its own -- yet it can reproduce, in a sense.
-
-
- CLEVELAND -- Tim Hnath, the
Fed Ex man, doesn't seem worried as he places the packages on the lab doorstep.
-
- Sure, he knows his cargo could be toxic. How could he
forget? The warning signs are everywhere: Biohazard. Caution. No food or
drink.
-
- But he's learned how to negotiate his way down this hall.
"If you ever see a room like this," Hnath warns a colleague,
"never walk across the red tape."
-
- Most people don't want to be anywhere near the infectious
agent that causes mad cow disease and its family of brain-wasting illnesses.
But at the medical school at Case Western Reserve University, they can't
get enough of it.
-
- Thanks to Hnath and his daily deliveries, scientists
here are amassing the world's largest collection of human tissue infected
by prions (pree-ons) -- the strangely misshapen proteins that are believed
to be causing all the trouble. What is a prion?
-
- As a result, they just may hold the key to a mystery
that has baffled scientists and cast a pall over this year's hunting season
-- whether humans are in any danger from deer and elk with chronic wasting
disease.
-
- If the animal disease ever does spread to humans, Dr.
Pierluigi Gambetti and his team at Case Western may be the first to spot
it.
-
- Gambetti has created, in effect, a first-alert system
for human prion disease in labs where the words "be careful"
take on a whole new meaning. Once inside these labs, explains one of Gambetti's
technicians, "everything that leaves here is incinerated -- except
us."
-
- Prion immersion
-
- Gambetti, an Italian-born expert in brain disorders,
has immersed himself for 18 years in prion diseases. So he has his own
theory about the one in the news now: chronic wasting disease (CWD), which
turned up in scattered deer and elk herds across the country (so far in
Minnesota, in a single elk).
-
- Like most scientists, he thinks it's unlikely to infect
people. But the evidence that humans are safe from CWD is circumstantial,
and no one is offering iron-clad guarantees, especially in the wake of
Britain's mad cow debacle, where the experts turned out to be wrong.
-
- So he and other scientists are trying to find out what
makes prions dangerous. "In other words, we want to know the enemy,"
he says.
-
- Long before mad cow and chronic wasting got their ghoulish
names, these types of diseases roamed the earth in relative obscurity.
In people, they would occur randomly at the rate of about one in a million;
and in some unlucky families, prion diseases run in the bloodline. Invariably,
these illnesses are gruesome and fatal, causing rapid dementia and death.
-
- It was only in 1996, when British health officials noticed
an unusual increase in people with one such illness -- Creutzfeldt-Jakob
disease (CJD) -- that they realized they had an entirely new problem on
their hands. Some people, they concluded, were getting sick from eating
tainted beef.
-
- Shortly after, Gambetti won a federal grant to set up
the National Prion Disease Pathology Surveillance Center on the shores
of Lake Erie. Now, he's asking doctors from all over the United States
to send him samples of suspected CJD cases, on a strictly voluntary basis.
This way, he hopes to be able to spot any suspicious trends -- as well
as study the rogue proteins that seem to be wreaking havoc in both animals
and humans.
-
- Lots of gloves
-
- Phyllis Scalzo, a lab technician, figures she may have
seen the deadly CJD infection once in 17 years before she went to work
for Gambetti. Now, it's all around her. It's in the freezers lining the
hall, and in a half-dozen metal cabinets where brain tissue is preserved
in white buckets. It's on the slides she prepares for testing. It's on
the equipment.
-
- And it's in the packages that greet her each morning.
Or so she must assume.
-
- "I'm going to be going through a lot of gloves,"
she explains.
-
- The danger is unspoken, and in many ways unknown. There's
no known case of anyone getting sick from handling the diseased tissue.
But then again, she's dealing with something that seems to defy the laws
of science.
-
- The prion is a protein that somehow gets twisted into
a deadly form. Once it does, it's nearly indestructible. It can withstand
temperatures of 1,100 degrees Fahrenheit, and disinfectants are useless
against it.
-
- It's the only known infectious agent that has no DNA
or genetic material of its own -- yet it can reproduce, in a sense. It
apparently triggers a chain reaction in other proteins, turning normal
ones astray. Eventually, they destroy cells in the brain, leaving it looking
like a sponge, pocked with holes.
-
- The whole thing once seemed so preposterous that Dr.
Stanley Prusiner, the scientist who discovered and named prions, was ridiculed
at first. In 1997, however, he won the Nobel Prize in medicine for his
discovery.
-
- The worst part is that the diseases have been uniformly
fatal. No exceptions.
-
- So Scalzo and her colleagues take no chances.
-
- Before she opens the mail, she slips on a disposable
lab coat, apron, booties and a splatter guard to cover her face. She'll
add two more sets of gloves before she moves the tissue samples -- which
arrive in special styrofoam coolers, packed in dry ice or preservative
-- to the biohazard table for closer inspection.
-
- She rips gloves on and off obsessively. No pair is worn
for more than a few minutes. She doesn't want to contaminate anything accidentally.
"That's the most important thing: Know where your hands are at all
times," she says. Your feet, too. Nobody wears the same shoes home.
-
- Gambetti's team is about to open an even more secure
lab where everyone will be covered head to toe at all times, and the garbage
will be steamed for hours in a device called an autoclave before it is
incinerated.
-
- Unusual obsession
-
- Gambetti remembers when he would examine such tissue
with his bare hands. It was in the early 1960s, when, as a young pathologist,
he would stumble on a rare case of CJD. Back then, it was little more than
a medical oddity.
-
- But in 1984, a mentor from his old medical school in
Bologna , Italy, sent him a curious brain sample. It came from a man who
developed incurable insomnia, went mad and died. Gambetti, an expert in
Alzheimer's disease, started looking for answers in the patient's brain
tissue. Then a second member of the family died in similar fashion; and
a second sample was sent to Gambetti. Ultimately, he discovered it was
a type of prion disease that ran in the unfortunate family. He named it
fatal familial insomnia.
-
- Thus began his obsession with collecting human prion
diseases. It was, he figured, the only way to see enough of these rare
cases to study them properly.
-
- Prion diseases have long been a mystery.
-
- The earliest known form is scrapie, found in sheep more
than 200 years ago. The story goes that it got its name when infected sheep
would start acting erratically and scrape themselves endlessly against
trees, as if scratching an itch.
-
- In the 1950s, a human disease called kuru turned up in
a tribe of cannibals in New Guinea, after women and children ate the brains
of relatives in a funeral ritual. They called it "the laughing death."
-
- Mad cow disease appeared suddenly in English cattle in
the 1980s, and it spread in epidemic proportions through animal herds.
It's believed that the disease started when cows ate feed that contained
ground-up, scrapie-infested sheep.
-
- Experts hastened to assure the British people that they
had no reason to worry -- after all, people had been eating scrapie-infested
sheep for hundreds of years and were none the worse for it. In an infamous
publicity stunt, the agriculture minister, John Gummer, and his 4-year-old
daughter chomped on burgers for the cameras in 1990. Six years later, the
first human cases were tied to tainted beef.
-
- So far, about 135 people have come down with the disease
in England and several European countries. Its victims plunge into depression
and dementia at an average age of 27, and die in about a year. The illness
is distinct enough that doctors call it "variant CJD." Given
the millions of people who ate beef, it's still exceptionally rare. Yet
even though the animal epidemic has been stopped -- by mass destruction
of Britain's cattle -- no one knows how many more human cases are incubating.
-
- In more than 250 reported cases worldwide, doctors have
inadvertently spread CJD from patient to patient through tainted surgical
equipment, transplant tissue and human growth hormone. Health officials
have warned brain surgeons and others to take extra precautions, but there
is no widely available test to check equipment or tissue for prions.
-
- The sobering experience in Britain prompted health officials
in the United States to take a fresh look at chronic wasting disease, which
first surfaced in Colorado deer 35 years ago. So far, animals in nine states
and two Canadian provinces have tested positive, including wild deer in
southwestern Wisconsin and a single captive elk in Minnesota. Yet CWD hasn't
been linked to a single case of human illness.
-
- Assessing risk
-
- Dr. William Hueston, a University of Minnesota veterinarian,
knows what a mad cow outbreak looks like. And this doesn't look like one
to him.
-
- As a scientist with the U.S. Department of Agriculture,
he helped investigate the outbreak in England in the late 1980s and early
1990s.
-
- By comparison, the threat of chronic wasting disease
doesn't keep him up at night. "We put all [the] evidence together,
and what it says is that there's no evidence that this is a disease that
rapidly spreads to humans," he says.
-
- Why not?
-
- First, the differences. In England, he says, "there
were tens of millions of people exposed" to tainted beef products;
here, eating venison and elk meat is far less common. In England, people
ate the most infected areas of sick cows, such as the brain and spinal
cord. As the old joke goes, he says, they "used everything but the
moo." U.S. hunters are being advised to take the prime cuts of venison
-- where prions are not thought to accumulate -- and leave the rest behind.
-
- Second, there's no sign that people get sick at higher
rates if they hunt or live in areas where chronic wasting disease has been
found for decades.
-
- Government investigators have checked out about a dozen
cases of CJD in hunters -- including two men who shared a cabin in Wisconsin
(Gambetti's lab ruled out a third suspected case). So far, no link to venison
has been found.
-
- "There are two errors we can make," Hueston
says. "One is to say something's safe when it's not. The other is
to say something's dangerous when it's not."
-
- A species barrier?
-
- Is there, as Hueston and others believe, a species barrier
protecting us?
-
- The answer may well be yes and no.
-
- For obvious reasons, no one's going to expose someone
intentionally to find out.
-
- But Byron Caughey, a scientist at the National Institutes
of Health's Rocky Mountain lab in Hamilton, Mont., tried to approximate
those conditions in a test tube. He and his colleagues took prions from
deer and elk with chronic wasting disease and exposed them to normal human
proteins.
-
- No one's sure how they work, but prions somehow "convert"
ordinary proteins and cause them to fold abnormally. Caughey and his colleagues
wanted to see whether deer prions did that to human proteins in test tubes.
-
- They found that some of the human proteins converted
to an "apparently toxic" state -- but not many. It was, Caughey
says, only about 1/10th to 1/20th the rate they see in deer-to-deer transmission.
"It was barely detectable," he says.
-
- To scientists, it was good news, suggesting a "molecular
incompatibility" between the species. But skeptics saw it as proof
of danger, and one mad cow Web site even posted the story with the headline:
"Chronic Wasting Disease transmits to humans."
-
- Says Caughey: "We got a borderline result. As such,
people interpret it however they wish, I'm afraid."
-
- To him, it's a mixed message. "We have to acknowledge
that there is some risk of CWD going into humans. But it's likely to be
relatively low."
-
- Detecting unknowns
-
- If it does transmit to humans, how will anyone know it
when they see it?
-
- "Very difficult, at this point, because you ask
me to recognize an unknown," says Gambetti. But if it's anything like
the mad cow experience, he says, a human form of CWD might look different
under the microscope, and possibly act differently, than other human prion
illnesses.
-
- Those, he says, are the "kind of indirect clues"
that they watch for. "So we will be ready to recognize these cases,
even if we don't know what it's going to look like."
-
- In the meantime, his lab and others are hoping animal
studies will shed more light. In Gambetti's lab, a genetic specialist,
Dr. Qingzhong Kong, has bred what he calls "humanized" lab mice
that have human, rather than mouse, proteins. Researchers want to know
whether these mice can acquire CWD.
-
- But even those tests won't be the final word.
-
- They may not know for sure unless they actually find
a human case of chronic wasting disease. And that's where Gambetti's center,
which reports to the U.S. Centers for Disease Control and Prevention, comes
in.
-
- If that day comes, he'll notify federal health officials
"and then shut the door and run," he says with a laugh. "I'm
the arm, but not the mouth, in this operation."
-
- But he doesn't shy away from the possibility. "My
loyalty is to the truth," he says. "The important thing is to
be as well prepared as possible."
-
- -- Maura Lerner is at mlerner@startribune.com.
-
- © Copyright 2002 Star Tribune. All rights reserved.
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- http://startribune.com/stories/1556/3391355.html
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