The Battalion
Wednesday • July 30,19 1
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Scientific discovery reveals structural flaw in AZT
NEW YORK (AP) — Ten years after AZT hit the
market, scientists say they’ve figured out why it does
not work better: Chemicaily, it’s a bad dance partner.
The discovery might lead to better weapons
against the AIDS virus, the researchers said. But the
company that makes AZT was skeptical.
AZT, the first drug approved for attacking HIV,
sabotages the virus’s attempts to reproduce itself. It
does not work perfectly, and HIV eventually spawns
mutant strains that resist the medication.
Many more anti-HIV drugs have come along
since AZT, but the drug is still widely used.
The new research studied what happens to AZT
once it gets into a person’s body.
An AZT molecule goes through an intricate dance
in a user’s cells. It has to be modified three times to
become effective against HIV, and to get that done,
it has to dance with three different molecular part
ners. These partners are enzyme molecules that latch
onto AZT one at a time, make a modification, and
then let go.
The dance goes fine with the first partner. The
problem comes with the second. When this enzyme
and the AZT molecule pair up, the enzyme is far less
efficient at making the crucial modification than it
should be.
This creates a boftleneck in the process, reducing
the amount of activated AZT that can be built up to
work on the AIDS virus.
What’s the problem? The AZT molecule is basi
cally stepping on the second partner’s toes, German
scientists report in the August issues of Nature Med
icine and Nature Structural Biology.
More precisely, the enzyme molecule has a
loop-like structure that’s important in making the
modification, and the AZT molecule has a pro
truding finger that bends this loop out of kilter.
That makes it harder for the enzyme to act, the re
searchers concluded.
So scientists might do well to design drugs that
avoid bending this loop, they said. Or they could
provide AZT with a new dance partner that’s more
cooperative.
That would involve giving patients a gene to make
their cells pump out an altered form of the enzyme,
one that isn’t hindered by AZT’s protruding finger,
they said.
Ramona lones, a spokeswoman for AZT maker
Glaxo Wellcome Inc., said the new work offers a bet
ter explanation for the processing glitch than scien
tists had before.
“We don’t think this one piece of information is
going to really change drug development that
much,” she said.
“But certainly any information added to the mix
is helpful.”
Stalling the AIDS virus
AZT (transcriptase inhibitors)
Inhibits virus production until the HIV becomes immune to it, often nine to
12 months. Then similar drugs such as ddl, ddC and 3TC can be used.
How it works The AZT molecule has to be modified in turn by three
different enzyme molecules in the user’s cells.
The problem Scientists have found that the shape of the second enzyme
interferes with the effectiveness of the AZT molecule.
The HIV virus splices its own genes into those
of the cell, turning it into a virus factory. Drugs
can inhibit the process at two crucial points.
SAQUINAVIR (protease inhibitors)
Cripples the protease enzyme, which is vital to
the late stages of reproduction of the HIV virus.
The virus’s surface binds it
tightly to the targeted cell.
RNA
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HIV VIRUS
iw*;
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IN
REVERSE TRANSCRIPTASE
The genes of the HIV virus are
made of RNA. To reproduce, the
virus has to translate them into
DNA using an enzyme called
reverse transcriptase.
/
The cell begins producing
viral proteins with the help
of a viral ■scissor" called
protease.
NEW HIV
■ vwra
The new viruses
leave the host
cell, entering the
bloodstream to
infect other cells.
The integrated DNA becomes a permanent part of the cell’s genetic
information, destroying its infection fighting ability.
Source: AP research
Pol Pot video revives memories for Cambodians
PHNOM PENH, Cambodia (AP) — Huddled
shoulder to shoulder, some on tiptoes, market ven
dors, shoppers and taxi drivers crowded around the
TV monitor to look at the man blamed for the
deaths of as many as two million Cambodians.
Boys and girls stood open-mouthed, eyeing the
feeble, white-haired man—a bogeyman from hor
ror stories suddenly become real.
Those old enough to remember him cried out in
amazement: “That’s him! That’s him!”
The footage of toppled Khmer Rouge chief Pol
Pot, obtained by a cameraman with American jour
nalist Nate Thayer, was broadcast Tuesday on TV
monitors in Phnom Penh’s central market and at
the historic temple, Wat Phnom.
ABC, which purchased the film, set up the mon
itors for its “Nightline” show to see how ordinary
Cambodians reacted to their first sight of the secre
tive guerrilla Pol Pot in 18 years. The footage showed
a humiliated, broken Pol Pot being tried by his for
mer Khmer Rouge comrades Friday and sentenced
to house arrest for life.
Pol Pot and the Khmer Rouge ruled Cambodia
from ’75-’79, killing hundreds of thousands of
people by starvation, overwork and systematic ex
ecution in a quest to transform the nation into a
Marxist agrarian utopia. Invading Vietnamese
forces eventually ousted Pol Pot, sending him and
his followers into the jungles to continue their
guerrilla war.
Most passers-by ignored the show Tuesday, in
ured to the 69-year-old guerrilla leader by years of
conflicting rumors about his whereabouts and even
his death and more worried about survival in a
country still suffering from his reign of terror.
The emotions of those who did stop ranged from
surprise to desire for a real trial, rather than the
spectacle the Khmer Rouge held to publicly dis
tance themselves from their longtime chief.
“I hate him. I wish they would just kill him,”
declared a taxi driver, who identified himself only
as Savoeun.
Hem Savi, 41, watched recalled awakening from
a Khmer Rouge interrogation session two decades
ago to find that her parents and six siblings had
been killed and thrown into a pit.
“I feel no pity for Pol Pot watching this,” she said.
Ke Chandara, 35, a.motorcycle taxi driver, said
he was surprised anyone — even the Khmer Rouge
— could catch and try Pol Pot, a nightmare figure of
magical stature to most Cambodians.
Ke Chandara, who said his father’s fingernails were
torn out by the Khmer Rouge, agreed with others that
the trial and punishment were not legitimate and that
Pol Pot should be tried by a U.N. tribunal.
“There’s no nation on earth that killed its people
in such a cruel way as Pol Pot,” said Ke Chandara.
Palestinian panel
urges dismissal
of Arafat Cabinet
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Addicts praise Swiss heroin subsidy
ZURICH, Switzerland (AP) — Mar
co, a soft-spoken 30-year-old, has
been hooked on heroin nearly half his
life. Finally, he wants to quit. The
courage he needs to try to start over
comes from a familiar source: Heroin.
Three times a day, Marco enters a
nondescript Zurich office building. He
picks up a syringe, needle and swabs
and sits in one of five office chairs. He
shoots up.
As the drug courses into his blood
stream, a medical doctor stands by.
Marco’s drug supplier is none other
than the Swiss government.
Marco is one of about 1,000 junkies
in a state-run program that prescribes
heroin to hard-core addicts in hopes
of guiding them back into mainstream
society —- and encouraging them to
kick their deadly habit.
The three-year experiment, while
controversial, has rendered impres
sive results.
Nearly 90 of the addicts have en
tered programs to help them fully
withdraw from the drug, although it’s
too soon to judge the success of their
efforts. What is perhaps even more
substantial are the side effects for the
junkies: lower rates of AIDS and oth
er infectious diseases and a dramat
ic drop in crime — saving the tax
payers money.
“The crime situation is much bet
ter, and the program’s cheap," says Urs
Vontobel, director of Crossline, one of
17 drug centers across Switzerland.
“And — above all — it works.”
Marco and about 40 other addicts
treated by Crossline each pay $ 10 for a
day’s supply of heroin.
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RAMALLAH, West Bank (AP) — A Palestinian legislative par;
el reported wide-ranging corruption Tuesday in all 18Palestir
ian ministries — including diversion of foreign aid donations
and urged Yasser Arafat to sack his entire cabinet.
Arafat spokesman Marwan Kanafani praised thereportam
said it provides “a strong basis” for a cabinet reshuffle thatArafe 1
was already planning. Yet lawmakers and some membersd
Arafat’s own administration faulted the panel for failing to &
amine Arafat’s role in any wrongdoing.
“The mismanagement starts from the top—way upontop
declared Husam Khader, a legislator from Nablus.
The investigating committee was formed in response^
state comptroller’s report that found $326 million of the fife- „
tinian autonomy government’s $800 million annual budget
been squandered through corruption or mismanagemew/.
While the legislative committee has no legal authority,it
report put Arafat on the spot — compelling him to either/?
pudiate his political allies or face rising public anger ovetS
nancial abuses.
The committee’s report blamed the cabinet for allegedly tf
ing to follow up reports of mismanagement and urget
“dissolve the entire cabinet” and replace it with one "madeif
of technocrats and qualified people.”
It recommended bringing three ministers to trial, i
Nabil Shaath, the chief Palestinian negotiator who was accusedti I 111111
charging his home phone and electric bills to the government.
Among allegations in the panel’s 60-page report, readalois! !W as
Mde
Tuesday to the Palestinian Legislative Council:
-Information and Culture Minister Yasser Abed Rabbousd ne
$7,500 from the ministry budget to pay for central heating at hi: ^Pf
house.
—Transportation Minister Ali Qawasmeh accepted bribesii
license cars that did not meet road standards.
—Civil Affairs Minister Jamal Tarifi gave illegal exemption
from customs duties for more than 4,300 cars — including
Jaguar for his father.
Charter bus crashes into river
Man chaperoning children's group dies
25 miles
STONY CREEK, Va. (AP) — A bus taking chil
dren on a black history tour plunged off Interstate
95 into a river Tuesday, killing a chaperone re
garded as a grandson to civil rights pioneer Rosa
Parks. The 34 others aboard were injured.
The bus, part of a Pathways to Freedom tour
co-sponsored by Parks’ civil rights foundation,
went off the road near this southern Virginia
town and hurtled down an embankment,
through trees and into the 5-foot-deep Not
toway River.
Most of the injured were treated at hospitals
and released, but four were seriously hurt, in
cluding the bus driver and a 16-year-old girl
who broke both ankles.
The driver, Don Toliver of Detroit, had a
hand and a foot amputated, said Gregory Reed,
an attorney for Parks.
Most of the passengers were able to scramble
out, though rescuers had to pull out three or four
people trapped in the bus, which tipped over on
its side in the water. The bus was carrying 29
youngsters, the driver and five chaperones.
The cause of the crash was not immediate
ly known.
“Everyone was strong. Everyone was help
ing,” said Patricia Ellis, 56, of Oxford, Ohio, a
chaperone. “The young people did not cry out
or yell. We are a family. We all have pain be
cause we lost a member of our family.”
Killed was 25-year-old Adisa Foluke of De
troit, whose mother, Anita Peek, is the director
of the Pathways to Freedom program. His aunt,
Elaine Steele, is the director of Parks’ founda
tion. Peek and Steele are sisters.
“He was just as close to me as if he was my
own grandson, and I felt that way about him,
and that’s how he felt about me,” Parks, 84,
said in Detroit as she waited for a flight to Vir
ginia. “I’m just hoping, though, that the young
people who survive will continue on with the
program.”
Some said they would.
“I have to now. I have to finish,” said Makia
Gibson, 18. “Until we cross the river into Toron
to, Canada, our program says that we are not
free. We have to press on for our freedom.”
Freedom riders during the civil rights move
ment had problems as well, said Nicole Hous
ton, 14, of Denver. “There were people that did
die and they had to move on with it,” she said.
The students, ages 11 through 18, came from
around the country to take part in a tour that be
gan three weeks ago in Charleston, S.C., to trace
the route of escaped slaves and stop in places im
portant to the civil rights movement. The tour
planned to visit 22 cities in 15 states and Canada
before ending Aug. 13 in Washington.
Parks had met with the students last week in
Montgomery, Ala., and had planned to join the
tour in Toronto, said Reed, her attorney.
The tour was sponsored by the U.S. Trans
portation Department, the Detroit-based Rosa &
Raymond Parks Institute for Self Development,
and Shoney’s restaurants, which in 1992 paid its
black workers and former employees $105 million
to settle a race discrimination lawsuit alleging
black applicants were turned away and black em
ployees consigned to kitchen chores.
Parks galvanized the civil rights cause in 1955
when she refused to give up her seat on a Mont
gomery, Ala., bus to a white passenger, as required
by law. That touched off a yearlong boycott of
Montgomery buses that lifted the Rev. Martin
Luther King Jr. to national prominence.
At the crash site, straight tracks on the grassy
shoulder showed no evidence the driver hit the
brakes. A red-and-white teddy bear hung out a
window. Shirts, socks and two bus seats float
ed inside the bus.
Wilbert Mickens, 46, said he and most of the
group were sleeping when he heard the bus
crashing through trees and windows breaking.
“For a man that can’t swim, it was terrifying,
but we didn’t worry about that,” he said. “We
just pulled them (the kids) out.”
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One of the most seriously injured was a tty
year-old girl who broke both ankles. $ £
“We’re sorry it happened, and we’re trying .
get to the bottom of what happened,” said- e
Brannon, a spokesman for Rite-Way 0# Vic
of Detroit, which operated the bus. Sod
times, these things happen.”