《science》揭开中药的面纱

hxq2007

Lifting the Veil on Traditional Chinese Medicine
Richard Stone*

DALIAN, CHINA--Genome, proteome, metabolome … herbalome? In the
latest industrial assault on nature's biochemical secrets, a Chinese
team in this seaside city is about to embark on a 15-year effort to
identify the constituents of herbal preparations used as medications
for centuries in China.

The Herbalome Project is the latest--and most ambitious--attempt to
modernize t raditional Chinese medicine (TCM). The venerable
concoctions--as many as 400,000 preparations using 10,000 herbs and
animal tinctures--are the treatment of choice and often the only
recourse for many in China. In the 1970s, TCM tipped off researchers
to qinghaosu, a compound in sweet wormwood whose derivatives are
potent antimalaria drugs. But TCM's reputation has been blackened by
uneven efficacy and harsh side effects, prompting critics to assail it
as outmoded folklore. \"TCM is not based on science but based on
mysticism, magic, and anecdote,\" asserts biochemist Fang Shi-min, who
as China's self-appointed science cop goes by the name Fang Zhouzi. He
calls the Herbalome Project \"a waste of research funds.\"

Hoping to rebut TCM critics, Herbalome will use high-throughput
screening, toxicity testing, and clinical trials to identify active
compounds and toxic contaminants in popular recipes. \"We need to
ensure that TCM is safe and also show that it is not just qinghaosu,\"
says Guo De-an, who leads TCM modernization efforts at the Shanghai
Institute of Materia Medica and is not involved in Herbalome. Initial
targets are cancer, liver and kidney diseases, and illnesses that are
difficult for Western medicine to treat, such as diabetes and
depression.

The Dalian Institute of Chemical Physics (DICP), one of the biggest
and best-funded institutes of the Chinese Academy of Sciences, won a
$5 million start-up grant to develop purification methods; the
Ministry of Science and Technology is reviewing the project with a
view to including it as a $70 million initiative in the next 5-year
plan to start in 2010. A planning meeting will be held at a Xiangshan
Science Conference--China's equivalent of a Gordon Research
Conference--in Beijing this spring.

Several TCM power players have thrown their weight behind the
initiative. \"It's the right time to start this project,\" says chemist
Chen Kai-xian, president of the Shanghai University of Traditional
Chinese Medicine. Herbalome should appeal to pharmaceutical firms, as
it could identify scores of drug candidates, says Hui Yongzheng, chair
of the Shanghai Innovative Research Center of Traditional Chinese
Medicine.

In many parts of the world, traditional medicine recipes are handed
down orally from one generation to the next. But in China,
practitioners more than 2000 years ago began to compile formulations
in compendia. Although in major cities Western medicine has largely
supplanted TCM, many Chinese still believe in TCM's power as
preventive medicine and as a cure for chronic ailments, and rural
Chinese depend on it. \"For most of us, when we feel unwell, we want to
take TCM,\" says chemist Liang Xinmiao of DICP.

Since the Mao Zedong era, the government has strongly supported TCM,
in part because it was too expensive to offer Western medicine to the
masses. It remains taboo for Chinese media to label TCM as
pseudoscience. \"Criticizing TCM is unthinkable to many Chinese and
almost like committing a traitorous act,\" says Fang.

Proponents insist that TCM has much to offer. But for every claimed
TCM success, there are reports of adverse effects from natural toxins
and contaminants such as pesticides. Dosages are hard to pin down, as
preparations vary in potency according to where and when herbs are
harvested. Quality can vary from manufacturer to manufacturer and from
batch to batch. \"That's why many people don't trust TCM,\" says Guo. In
the modernization drive, quality control is a paramount concern.

Herbalome intends to take modernization to a whole new level. The
initiative is the brainchild of Liang, who believes many TCM recipes
are effective. \"The problem is, we don't know why it works,\" he says.
The main hurdle is the complexity of the preparations. As an example,
Liang shows a chromatograph of Hong Hua, or \"red flower,\" a
preparation applied externally for muscle pain. In many samples
chemists deal with, one peak usually represents one compound, Liang
says. But for Hong Hua, each peak is many compounds, and fractionating
these yields more multicompound peaks like nested matryoshka dolls.
Hong Hua is composed of at least 10,000 compounds, says Liang: \"We
know only 100.\"

Faced with such complexity, \"we must invent new methodologies,\" says
Liang. \"This is the battleground of the Herbalome project.\" For
starters, his 45-person team at DICP is developing new separation media.
Herbs will be parsed into \"multi-components\": groups of similar
constituents. To determine which substances are beneficial or toxic,
his group plans to devise Herbalome chips in which arrays of compounds
are screened for their binding to key peptides. The expanded Herbalome
project would involve researchers at many institutes in China and
abroad.

Herbalome has potential pitfalls. One is a concern that Western
companies will develop blockbuster drugs--and walk away with the
spoils--by modifying compounds identified by the project. To counter
this possibility, says Guo, \"we're encouraging scientists not to rush
to publish and do structure modifications [to identify drug candidates]
first.\" Teams would then apply for patents on groups of similar
structures.

Not all practitioners embrace TCM's demystification. \"Some are afraid
that the traditions will be lost,\" says Chen. But Hui says that
modernization is necessary \"to reconcile the knowledge-oriented,
deductive process of Western medicine with the experience-oriented,
inductive process of TCM.\" Fang has a different take: \"Can you marry
astrology and astronomy, alchemy and chemistry? It never works.\"

Hui insists that TCM can coexist wi th Western medicine. Liang hopes
his Herbalome project will prove Hui right.

With reporting by Li Jiao in Beijing.