i****g
发帖数: 3896 | 1 老外也开始关注青蒿素发现的争议了。
http://www.nytimes.com/2012/01/17/health/for-intrigue-malaria-d
The Chinese drug artemisinin has been hailed as one of the greatest advances
in fighting malaria, the scourge of the tropics, since the discovery of
quinine centuries ago.
Luigi Rignanese
Artemisinin’s discovery is being talked about as a candidate for a Nobel
Prize in Medicine. Millions of American taxpayer dollars are spent on it for
Africa every year.
But few people realize that in one of the paradoxes of history, the drug was
discovered thanks to Mao Zedong, who was acting to help the North
Vietnamese in their jungle war against the Americans. Or that it languished
for 30 years thanks to China’s isolation and the indifference of Western
donors, health agencies and drug companies.
Now that story is coming out. But as happens so often in science, versions
vary, and multiple contributors are fighting over the laurels. That became
particularly clear in September, when one of the Lasker Awards — sometimes
called the “American Nobels” — went to a single one of the hundreds of
Chinese scientists once engaged in the development of the drug.
Mao’s role was simple.
In the 1960s, he got an appeal from North Vietnam: Its fighters were dying
because local malaria had become resistant to all known drugs. He ordered
his top scientists to help.
But it wasn’t easy. The Cultural Revolution was reeling out of control, and
intellectuals, including scientists, were being publicly humiliated, forced
to labor on collective farms or even driven to suicide. However, because
the order came from Mao himself and he put the army in charge, the project
was sheltered. Over the next 14 years, 500 scientists from 60 military and
civilian institutes flocked to it.
Meanwhile, thousands of American soldiers in Vietnam were also getting
malaria, and the Walter Reed Army Institute of Research began its own drug
hunt. That effort ultimately produced mefloquine, later sold under the brand
name Lariam.
While powerful, mefloquine has serious drawbacks, including nightmares and
paranoia. In 2003, dozens of American Marines in Liberia got malaria after
refusing to take pills because of military scuttlebutt that several Special
Forces soldiers who killed their wives after returning home from Afghanistan
in 2002 had been driven insane by the drug.
China’s effort formally began at a meeting on May 23, 1967, and was code-
named Project 523, for the date.
Researchers pursued two paths. One group screened 40,000 known chemicals.
The second searched the traditional medicine literature and sent envoys into
rural villages to ask herbal healers for their secret fever cures.
One herb, qinghao, was mentioned on tomb carvings as far back as 168 B.C.
and praised on medical scrolls through the centuries, up to the 1798 Book of
Seasonal Fevers. Rural healers identified qinghao as what the West calls
Artemisia annua, or sweet wormwood, a spiky-leafed weed with yellow flowers.
In the 1950s, officials in parts of rural China had fought malaria outbreaks
with qinghao tea, but investigating it scientifically was new. It also had
at least nine rivals from traditional medicine with some anti-malarial
effects, including a pepper.
In the lab, qinghao extracts killed malaria parasites in mice. Researchers
tried to find exactly which chemical worked, which plants had the most,
whether it could cross the blood-brain barrier to fight cerebral malaria,
and whether it worked in oral, intravenous and suppository forms.
Outmoded equipment slowed research. But by the 1970s it was known that the
lethal chemical, first called qinghaosu and now artemisinin, had a structure
never seen before in nature: In chemical terms, it is a sesquiterpene
lactone with a peroxide bridge. Trials in 2,000 patients showed that it
killed parasites remarkably rapidly.
However, the body eliminated it so fast that any parasites it missed made a
comeback. So scientists began mixing it with slower but more persistent
drugs, creating what is now called artemisinin combination therapy. (One new
combination includes mefloquine.)
A 2006 history of the project by Zhang Jianfang, its former deputy director,
contains some gripping details: petty disputes between rivals, Cultural
Revolution street fighting that forced one laboratory into a basement,
project doctors’ living on brown rice and vegetables as they did clinical
trials in remote villages in China’s tropical southern mountains, and other
doctors’ hiking the Ho Chi Minh Trail with the Vietcong.
Mao died in 1976; Project 523 was officially disbanded in 1981, though
clinical work continued.
In 1979, Dr. Keith Arnold, a malaria researcher in Hong Kong who had helped
the Army develop mefloquine, wangled his way into China, hoping to test his
drug there. He met Dr. Li Guoqiao, who was testing artemisinin variants.
They decided to try head-to-head trials, and the Chinese mystery drug beat
his, Dr. Arnold said.
Soon, World Health Organization scientists asked for articles from China’s
medical journals, the first of which had been published in 1977, in response
to reports that a Yugoslav chemist was experimenting with wormwood.
Enlarge This Image
EARLY CURE An illustration from the 1941 Bulletin of the History of Medicine
depicted the idea that quinine’s source, the cinchona tree, was named for
a countess in Peru
Related
Health Guide: MalariaIn 1982, The Lancet had an article by Chinese
researchers. It won a prize, but the check, in British pounds, could not be
cashed in China.
Shortly thereafter, Dr. Arnold said, Walter Reed scientists found wormwood
growing on the banks of the Potomac and extracted artemisinin. Nonetheless,
the drug languished. The W.H.O. did not endorse it until 2000, and it was
not widely available until 2006.
The reasons for that delay are disputed. China was in political disarray.
Different labs in and outside China were working on derivatives. Patent law
had vanished under communism, and China never took out Western patents, so
there was no way a major drug company could get a monopoly and make big
profits. Malaria was a disease of the poor, and today’s big donor funds did
not exist.
Aid agencies could not buy drugs that were not W.H.O.-approved. For years,
Dr. Arnold said, he tried to get permission for his Chinese collaborators to
do clinical trials in Thailand and Vietnam, but the W.H.O. stalled. (As a
United Nations agency, it is rarely bold, but the 1990s were a decade of
particularly low morale and constant infighting.)
As nearly one million African children a year died, Dr. Arnold denounced its
indecisiveness as “genocidal.”
The American military stuck with mefloquine, despite its expense. As late as
2002, as Doctors Without Borders clamored for artemisinin, an adviser to
the United States Agency for International Development dismissed it in an
interview with The New York Times as “not ready for prime time” and
defended chloroquine and other old, cheap drugs even though resistance to
them was widespread.
A Swiss company, Novartis, finally broke the logjam. It bought a new Chinese
patent on a mix of artemether, an artemisinin derivative, and lumefantrine,
another Chinese drug, and took out Western patents, planning to sell it
under the name Riamet at high prices to tourists and militaries; in 2001, it
agreed to sell it nearly at cost to the W.H.O. under the name Coartem.
The money to buy the drug on a large scale became available with the
creation of the Global Fund to Fight AIDS, Tuberculosis and Malaria in 2002
and the Bush administration’s introduction of the President’s Malaria
Initiative in 2005. Now, about 150 million doses of several combinations are
bought for poor countries each year.
With that victory, surviving Project 523 scientists and some outsiders began
vying for credit. In 1996, a Hong Kong science foundation recognized 10
team leaders. In 2009, Zhou Yiqing got the European Patent Office’s “
Inventors of the Year” award for Coartem.
In September, the $250,000 Lasker Award for clinical medical research was
given to Dr. Tu Youyou, former chief of the Institute of Chinese Materia
Medica in Beijing. The Lasker committee named her “the discoverer of
artemisinin.”
Some Chinese and Western malariologists were outraged.
Dr. Nicholas J. White, a prominent Oxford malaria researcher, said it was “
not fair to credit this discovery to one individual”; he named others he
considered equally deserving, including the clinical trial leader, Dr. Li,
and a chemist, Li Ying.
Dr. Arnold, whose work with Dr. Li was mentioned in the Lasker citation,
agreed. Richard K. Haynes, a malaria researcher and historian at the
University of Science and Technology in Hong Kong, called naming one
inventor “a travesty.”
The Lasker Foundation declined to comment, other than to note that Dr. Tu’s
citation mentioned that Project 523 was a large collaborative effort.
In an interview before the ceremony, Dr. Tu, 81, argued that she deserved it
because her team had been the first to isolate qinghao’s active ingredient
while other teams worked on the wrong plants.
Also, after rereading a manuscript by Ge Hong, a fourth-century healer,
prescribing qinghao steeped in cold water for fever, she realized that
boiling, the typical extraction method, was destroying the active ingredient
. She switched to ether, and qinghao became the first plant extract 100
percent effective at killing malaria in mice.
And before human testing began, Dr. Tu said, she and two colleagues took it
themselves to make sure it was not toxic.
Before the West even heard of the drug, she said, she was one of the four
anonymous authors of the initial 1977 paper, and in 1978, she was chosen to
accept the Chinese government’s overall award to Project 523.
However difficult winnowing the field would prove, the Nobel Prize committee
would be forced to do it anyway. The Nobel rules specify no more than three
winners. And no posthumous prizes, either — meaning Mao would be out of
the question. | j*****d
发帖数: 787 | 2 NYT 的记者就是够 2B 阿
NOBEL字眼全文只出现4次，最后一段就出现了两次，还捎带调戏老毛，活腻了。
advances
for
【在 i****g 的大作中提到】
: 老外也开始关注青蒿素发现的争议了。
: http://www.nytimes.com/2012/01/17/health/for-intrigue-malaria-d
: The Chinese drug artemisinin has been hailed as one of the greatest advances
: in fighting malaria, the scourge of the tropics, since the discovery of
: quinine centuries ago.
: Luigi Rignanese
: Artemisinin’s discovery is being talked about as a candidate for a Nobel
: Prize in Medicine. Millions of American taxpayer dollars are spent on it for
: Africa every year.
: But few people realize that in one of the paradoxes of history, the drug was
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