j*****d
发帖数: 787 | 1 P.S.
vedio interview
http://www.laskerfoundation.org/awards/2011_c_interview_youyou.
and the comments wrote by Tu Youyou herself in Nature Medicine: http://www.laskerfoundation.org/awards/pdf/2011_c_youyou.pdf
and the publications authored by her and her colleague
http://www.laskerfoundation.org/awards/2011_c_keypub_youyou.htm
the report from JCI
http://www.jci.org/articles/view/60887
the essay from Cell （中文）
http://www.cell.com/LaskerAward-Chinese
科学时报新闻（国内媒体）
http://news.sciencenet.cn/htmlnews/2011/9/252330.shtm
and her email :-)
y************[email protected]
Lasker~DeBakey
Clinical Medical Research Award
Award Description
Tu Youyou
For the discovery of artemisinin, a drug therapy for malaria that has saved
millions of lives across the globe, especially in the developing world.
The 2011 Lasker~DeBakey Clinical Medical Research Award honors a scientist
who discovered artemisinin and its utility for treating malaria. Tu Youyou (
China Academy of Chinese Medical Sciences, Beijing) developed a therapy that
has saved millions of lives across the globe, especially in the developing
world. An artemisinin-based drug combination is now the standard regimen for
malaria, and the World Health Organization (WHO) lists artemisinin and
related agents in its catalog of "Essential Medicines." Each year, several
hundred million people contract malaria. Without treatment, many more of
them would die than do now. Tu led a team that transformed an ancient
Chinese healing method into the most powerful antimalarial medicine
currently available.
Malaria has devastated humans for millennia, and it continues to ravage
civilizations across the planet. In 2008, the mosquito-borne parasites that
cause the illness, Plasmodia, infected 247 million people and caused almost
one million deaths. The ailment strikes children particularly hard,
especially those in sub-Saharan Africa. It affects more than 100 countries—
including those in Asia, Latin America, the Middle East, parts of Europe—
and travelers from everywhere. Symptoms include fever, headache, and
vomiting; malaria can quickly become life-threatening by disrupting the
blood supply to vital organs. Early diagnosis and treatment reduces disease
incidence, prevents deaths, and cuts transmission.
In the late 1950s, the WHO embarked on an ambitious project to eradicate
malaria. After limited success, the disease rebounded in many places, due in
part to the emergence of parasites that resisted drugs such as chloroquine
that had previously held the malady at bay. At the beginning of the Chinese
Cultural Revolution, the Chinese government launched a secret military
project that aimed to devise a remedy for the deadly scourge. China was
particularly motivated to prevail over malaria not only because it was a
significant problem at home, but also because the Vietnamese government had
asked for help. It was at war and the affliction was devastating its
civilian and military populations.
The covert operation, named Project 523 for the day it was announced—May 23
, 1967—set out to battle chloroquine-resistant malaria. The clandestine
nature of the enterprise and the political climate created a situation in
which few scientific papers concerning the project were published for many
years, the earliest ones were not accessible to the international community,
and many details about the endeavor are still shrouded in mystery. In early
1969, Tu was appointed head of the Project 523 research group at her
institute, where practitioners of traditional medicine worked side by side
with modern chemists, pharmacologists, and other scientists. In keeping with
Mao Zedong's urgings to "explore and further improve" the "great treasure
house" of traditional Chinese medicine, Tu combed ancient texts and folk
remedies for possible leads. She collected 2000 candidate recipes, which she
then winnowed. By 1971, her team had made 380 extracts from 200 herbs. The
researchers then assessed whether these substances could clear Plasmodia
from the bloodstream of mice infected with the parasite.
One of the extracts looked particularly promising: Material from Qinghao (
Artemisia annua L., or sweet wormwood) dramatically inhibited parasite
growth in the animals. Such hopeful results, however, were not reproducible,
so Tu dove back into the literature and scoured it for possible
explanations.
The first known medical description of Qinghao lies in a 2000-year-old
document called "52 Prescriptions" (168 BCE) that had been unearthed from a
Mawangdui Han Dynasty tomb. It details the herb's use for soothing
hemorrhoids. Later texts also mention the plant's curative powers. Tu
discovered a passage in the Handbook of Prescriptions for Emergencies (340
CE) by Ge Hong that referenced Qinghao's malaria-healing capacity. It said "
Take a handful of Qinghao, soak in two liters of water, strain the liquid,
and drink." She realized that the standard procedure of boiling and high-
temperature extraction could destroy the active ingredient.
With this idea in mind, Tu redesigned the extraction process, performing it
at low temperatures with ether as the solvent. She also removed a harmful
acidic portion of the extract that did not contribute to antimalarial
activity, tracked the material to the leaves rather than other parts of the
plant, and figured out when to harvest the herb to maximize yields. These
innovations boosted potency and slashed toxicity. At a March 1972 meeting of
the Project 523 group's key participants, she reported that the neutral
plant extract —number 191—obliterated Plasmodia in the blood of mice and
monkeys.
From branch to bedside
Later that year, Tu and her team tested the substance on 21 people with
malaria in the Hainan Province, an island off the southern coast of China.
About half the patients were infected with Plasmodium falciparum, the
deadliest of the microbial miscreants, and about half were infected with
Plasmodium vivax, the most common cause of a disease variant that is
characterized by recurring fevers. In both groups, fever disappeared rapidly
, as did blood-borne parasites.
In the meantime, Tu started to home in on the active ingredient, using
chromatography to separate the extract's components. On November 8, 1972,
she and her colleagues obtained the pure substance. They named it Qinghaosu
(literally, the principle of Qinghao) and it is now commonly called
artemisinin in the west. Tu and her colleagues subsequently determined that
it had an unusual structure. It proved to be a sesquiterpene lactone with a
peroxide group, a completely different kind of compound than any known
antimalarial drug. Later studies would show that the peroxide portion is
essential for its lethal effects on the parasite.
Subsequent clinical trials on 529 malaria cases confirmed that the crystal
they had isolated delivers the antimalarial blow. Many scientists from other
institutes then joined efforts to improve the extraction procedures and
conduct clinical trials. The first English language report about artemisinin
was in December 1979; as was customary at the time in China, the authors
were anonymous. By that point, the China-wide Qinghaosu research group had
given the substance to more than 2000 patients, some of whom had chloroquine
-resistant P. falciparum malaria infections. In addition, the drug cured 131
of 141 individuals with cerebral malaria, a particularly severe form of the
disease. Comparative studies on a small number of cases suggested that the
drug acted more quickly than chloroquine did. The investigators reported no
harmful side effects.
The paper drew international attention. In October 1981, the scientific
working group on the chemotherapy of malaria, sponsored by the WHO, the
World Bank, and United Nations Development Business, invited Tu to present
her findings at its fourth meeting. Her talk evoked an enthusiastic response
. She told the audience not only about artemisinin, but also about some of
its chemical derivatives. In 1973, as part of her structural studies, Tu had
modified artemisinin to generate a compound called dihydroartemisinin. She
later found that it delivers ten times more punch than artemisinin and that
it reduces risk of disease recurrence. This compound provided the basis for
other artemisinin-derived drugs. Starting in the mid 1970s, Guoqiao Li (
Guangzhou College of Traditional Chinese Medicine) performed clinical trials
with artemisinin and these substances. They all delivered more therapeutic
clout than did standard drugs such as chloroquine and quinine. The
derivatives tend to hold up better than the parent compound in the body, and
they form the foundation of today's therapies.
In 1980, Keith Arnold (Roche Far East Research Foundation, Hong Kong) joined
Li's enterprise and two years later, they published the first high-profile
clinical trial of artemisinin in a peer-reviewed, western journal. The same
group then conducted the first randomized studies that compared artemisinin
alone with the known anti-malarial agents, mefloquine and Fansidar (
sulfadoxine-pyrimethamine). Artemisinin enhanced effectiveness without
adding side effects. Li, Arnold, and others subsequently showed that
suppository forms of artemisinin and its derivatives are effective. This
mode of drug delivery is especially important for babies and unconscious
patients.
Almost every new antimalarial drug has initially slashed incidence of the
disease, and then the parasites stop succumbing to it. At that point,
sickness and death rates climb again. Small pockets of resistance to
artemisinin-based compounds have already cropped up in Western Cambodia. To
avoid resistance, patients typically take two drugs that attack the parasite
in different ways, and since 2006, the WHO has discouraged use of
artemisinin compounds as solo therapies. The organization now recommends
several combination treatments, each of which contain an artemisinin-based
compound plus an unrelated chemical.
In 2001, the WHO signed an agreement with Novartis, the manufacturer of one
of these drug combinations, Coartem®; it consists of artemether and
lumefantrine, another antimalarial agent, which was originally synthesized
by the Academy of Military Medical Sciences in Beijing. The company is
supplying the drug at no profit to public health systems of countries where
the disease is endemic. To date, Novartis has provided more than 400 million
Coartem® treatments.
Tu pioneered a new approach to malaria treatment that has benefited hundreds
of millions of people and promises to benefit many times more. By applying
modern techniques and rigor to a heritage provided by 5000 years of Chinese
traditional practitioners, she has delivered its riches into the 21st
century.
By Evelyn Strauss |
