http://www.signonsandiego.com/news/science/20050202-9999-lz1c2vulture.html

"Eventually, the biologists realized that the best way to beat the dogs
to the carcasses was to look for birds that tangled in tree limbs when
they died, rather than falling to the ground. When the locals found out
what was needed, Oaks added, "we created a nice little cottage industry
in tree-climbing."

Immediately one drug stood out.

Diclofenac (pronounced dye-KLO-fen-ak) is a nonsteroidal
anti-inflammatory drug (NSAID) commonly used by arthritis sufferers.
Recently, Indian and Pakistani veterinarians had started using it for
livestock, as well. A few inexpensive injections can get an arthritic
cow or water buffalo back on its feet, a valuable boon in a culture
where farmers still use animals for plowing.

NSAIDs are typically considered safe for cattle and water buffalo
(although some, such as Vioxx, have come under scrutiny due to links to
heart attacks in humans). But overdoses of NSAIDs can cause kidney
damage. Doctors and veterinarians know what doses are safe for people
and cattle, but nobody had ever tested them in birds. And, Oaks was
soon to discover, birds - or at least vultures - are unusually
sensitive to kidney damage from NSAIDs.

All that remains

Asian vulture populations are being felled at an alarming rate by
arthritis drug

By Richard A. Lovett
UNION-TRIBUNE

February 2, 2005

BERNARD CASTELEIN / Naturepl.com

Scientists believe three species of vultures on the Indian
subcontinent, including the Oriental white-backed vulture (above), will
likely become extinct in the near future.

When the first Europeans arrived in America, one of the most numerous
birds was the passenger pigeon, which, as recently as the mid-1800s,
darkened the skies in flocks containing hundreds of thousands or even
millions of birds. But by 1914, the birds were gone - exterminated by
hunting and habitat destruction in one of the most dramatic die-offs in
history.

Today, a depressingly similar die-off is occurring in India and
Pakistan, and again, humans are the cause. As recently as a decade ago,
tens of millions of vultures ranged across India, Pakistan, Nepal and
neighboring countries. These birds we

re believed to be the most numerous raptors in the world, so numerous
that nobody even bothered to count them, says Rick Watson, director of
international programs for The Peregrine Fund, headquartered in Boise,
Idaho.

Historically, the birds coexisted easily with humans because farmers
had discovered that they served as efficient, inexpensive cleanup
crews. When an aging cow or water buffalo died, there was no need to
bury it; you simply hauled the carcass to a field and left it for the
vultures. Biologists estimate that in the 1990s, dead farm animals were
the birds' primary source of food.

But in 1999, naturalists reported a decline in vultures in parts of
India - a decline that has continued at alarming rates. Where once a
buffalo carcass might have drawn a hundred or more birds, today's
carcasses often draw no vultures at all, says J. Lindsay Oaks, a
professor of veterinary medicine at Washington State University.

Oaks is part of a team of researchers recruited by The Peregrine Fund
to investigate the vultures' decline. In 2000, the scientists staked
out the three largest remaining vulture-nesting sites, in Pakistan. At
the time, these sites had a total of about 1,500 breeding pairs. Now,
there are no vultures left at two of the sites, and the third is down
to less than a quarter of its original numbers.

The goal, however, was to do more than simply catalog the birds'
decline. In a scientific detective story ranging from Pakistan to San
Diego, team members pursued the killer, finding that, for once, it had
nothing to do with hunting or habitat encroachment. Rather, the culprit
proved to be a surprising side effect of a drug called diclofenac, a
normally benign substance in the same family as ibuprofen.

Toxin search

Like any good episode of the hit TV series "CSI," the diclofenac story
begins with experts studying a dead body. Or in this case, many bodies.
But first, the scientists needed to collect dead birds for examination,
something that proved unexpectedly difficult. "We thought that with all
of these birds dying, it would be easy to get samples," says Oaks. "But
it required an intensive amount of manpower."

The problem was that the biologists faced stiff competition from wild
dogs. "Anything sick or dead that hit the ground got scavenged, right
away," Oaks explained at a meeting of the Society of Environmental
Toxicology and Chemistry, last fall in Portland, Ore. "Here we were,
witnessing one of the greatest bird die-offs in history, but it was
hard to get specimens."

Eventually, the biologists realized that the best way to beat the dogs
to the carcasses was to look for birds that tangled in tree limbs when
they died, rather than falling to the ground. When the locals found out
what was needed, Oaks added, "we created a nice little cottage industry
in tree-climbing."

That allowed the team to collect 259 birds, most of which proved to
have died of kidney failure. That's an easy condition to diagnose, Oaks
says, because it causes uric acid, a substance normally excreted by the
kidneys, to accumulate in the birds' bodies, coating their internal
organs in a white crust called "visceral gout."

But knowing that the birds were dying of kidney failure wasn't the same
thing as knowing why their kidneys had failed. The biologists therefore
took tissue samples from 28 birds that had died of visceral gout and 14
others that died of other causes, such as being struck by automobiles.
These samples were then shipped to Oaks' lab in Pullman, Wash., which
then shipped microscope slides to Bruce Rideout, chief pathologist at
the San Diego Zoo.

In retrospect, Rideout says, one of the team's greatest accomplishments
was studying these samples systematically, rather than single-mindedly
trying to confirm a predetermined hypothesis. "When something
catastrophic like this happens, there's a temptation to jump to a
conclusion," he says. "And because of the way it was spreading, a lot
of investigators assumed this had to be an infectious disease."

But infectious diseases don't usually cause visceral gout, and the
kidney damage didn't look like anything normally caused by viruses or
bacteria. That's because infections cause white blood cells to rush to
the site of the infection, and Rideout and the other pathologists found
little sign of the type of inflammation this would cause.

Although the team continued to cover its bases by searching for a
pathogen, Oaks and Rideout were already wondering whether the birds
were being killed by a fast-acting toxin. To test this, they conducted
toxicological screens for what Oaks calls the "usual suspects,"
including heavy metals and pesticides. But the results came up
negative.

Having ruled out the obvious, Oaks turned to the not-so-obvious. In
particular, he began wondering whether there could be a link to the
fact that the birds ate dead farm animals. Could something in the
livestock be toxic?

To find out, he compiled a list of veterinary drugs sold in India and
Pakistan, looking for something known to cause kidney damage -
something that had only recently come into widespread use.

Immediately, one drug stood out.

Diclofenac (pronounced dye-KLO-fen-ak) is a nonsteroidal
anti-inflammatory drug (NSAID) commonly used by arthritis sufferers.
Recently, Indian and Pakistani veterinarians had started using it for
livestock, as well. A few inexpensive injections can get an arthritic
cow or water buffalo back on its feet, a valuable boon in a culture
where farmers still use animals for plowing.

NSAIDs are typically considered safe for cattle and water buffalo
(although some, such as Vioxx, have come under scrutiny due to links to
heart attacks in humans). But overdoses of NSAIDs can cause kidney
damage. Doctors and veterinarians know what doses are safe for people
and cattle, but nobody had ever tested them in birds. And, Oaks was
soon to discover, birds - or at least vultures - are unusually
sensitive to kidney damage from NSAIDs.

Uncertain future

The first confirmation came when the scientists ran new chemical tests
and found traces of diclofenac in all the birds that had died of the
mystery disease - and none in those that died of other causes.

That's about as close to finding a smoking gun as a statistical
analysis can ever come, but the researchers still needed to prove that
an animal carcass could contain a fatal dose of diclofenac. Therefore,
the biologists in Pakistan treated goats and water buffalo with the
drug, butchered them, and fed the meat to injured vultures that would
have been euthanized, anyway.

Most died of kidney failure, particularly those that gorged most
heavily on the contaminated meat. Oaks' team reported its findings a
year ago in the journal Nature. But skeptics still questioned whether
diclofenac use could be widespread enough to account for the rate at
which the vultures were dying.

A team of British researchers led by Rhys Green, of England's Royal
Society for the Protection of Birds, set out to find the answer. In a
study published last year in the journal Applied Ecology, the team
created a computer simulation of vultures eating water buffalo
carcasses. They found that given the birds' feeding habits, the
population would indeed crash if as few as 1 in 130 carcasses (and
possibly as few as 1 in 760) contained diclofenac.

In addition, Oaks' market studies found that large quantities of
veterinary drugs, including diclofenac, are indeed used in Asia. "It's
widely available," he says, "and cheap."

Luckily, there appears to be little risk to vultures in other parts of
the world, such as Africa, where such drugs might also be inexpensive
and widely available. That's because Africans do not dispose of
carcasses by leaving them for scavengers, says Rideout. They're also
much more likely to butcher animals before they become old enough to
develop arthritis.

But the future looks bleak for Asian vultures. "There are three
different species," says Watson. "Of these, the slender-billed vulture
is in such low numbers that last year we only knew of one or two
breeding pairs, anywhere. This species may already be functionally
extinct (meaning that there are no longer enough animals to reproduce
in the wild)."

As for the other two species, one is the Oriental white-backed vulture,
which his team has been monitoring in Pakistan. Although this year's
count isn't complete, it appears that the largest surviving colony is
down to about 100 pairs.

And that's only because last year, once diclofenac was discovered to be
the culprit, his team managed to slow that colony's demise by setting
up a "vulture restaurant" of uncontaminated food. Even so, the number
of birds has fallen by approximately 35 percent since last year.

The third species, the long-billed vulture, tends to live in very
remote locations and is less severely affected. "I would give that
species a few years until extinction," Watson says.

One solution

In America, we might be able to react quickly to a straightforward
problem, once the cause is known. In fact, Oaks says, we've already
dealt with a similar concern by making it illegal for farmers to allow
scavengers to eat carcasses of animals "put down" with certain drugs,
because the drugs can kill eagles.

But so far, only one Indian state, Gujarat, has taken official action,
prohibiting state-employed veterinarians from using diclofenac. That
sounds like a positive move, but given the ready access to the drug in
village stores, it would take much more than that to halt the birds'
decline.

In the short run, the answer is captive breeding. Luckily, two of the
leading organizations involved - the San Diego Zoo and The Peregrine
Fund - have extensive experience with such programs. In fact, The
Peregrine Fund was created in 1970 to save peregrine falcons from
extinction when it was discovered that their populations were being
decimated by DDT. (Now, peregrines are again thriving in the wild.)

Rideout is optimistic that future generations will also watch vultures
soar the skies of Asia. "The fact that we got answers very quickly," he
adds, "will enable us to intervene and make sure that they don't become
the passenger pigeons of the 21st century."

Watson is a little less sanguine. U.S. animal-importation rules make it
necessary to carry out the captive breeding program in Asia, he says,
and so far, nobody has stepped forward to do the work. "Breeding birds
of prey in captivity is really a lifestyle, rather than a job," he
says. "We haven't yet found individuals willing to dedicate their lives
to it, and that's what it takes. The key is finding those individuals."

Richard Lovett is a freelance writer in Portland, Ore. and frequent
contributor to Quest.