impaginato piccolo - Società Italiana di Parassitologia (SoIPa)

Parassitologia 50: 25-29, 2008
Artemisinins from Folklore to Modern Medicine - Transforming
an Herbal Extract to Life-Saving Drugs
P.J. Weina
Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland 20910
Abstract. The history of the artemisinins from Ge Hong in China during the 4 th century, to the re-discovery
of the qing hao derivatives in the 1970s, to the explosion of artemisinin derivatives and combinations
throughout the world today is a fascinating story. The central and underappreciated role of the United
States Army’s ‘drug company’ known as the Division of Experimental Therapeutics at the Walter Reed Army
Institute of Research is a story worth relating. From being the first group outside China to extract the active
component of qing hao, to leading the work on neurotoxicity of the class in animals, to bringing a Good
Manufacturing Practices intravenous formulation to the worldwide market is traced.
Keywords: Malaria, Artemisinin, Artesunate, Qing hao.
The Walter Reed Army Institute of Research (WRAIR)
has a group within it called the Division of
Experimental Therapeutics. This small of group of
physicians and scientists comprise one of the most
influential, successful, but relatively unknown antimalarial
drug programs in the world. Since World War
II, this group has filed over sixty Investigational New
Drug Applications with the U.S. Food and Drug
Administration for antimalarials and have had a hand
in virtually every antimalarial licensed in the developed
world. And yet, with all of this history, most of the
older researchers and military officers at the WRAIR
can still remember the first time they heard about
artemisinin. At the time, few people knew it by this
name though. Artemisinin was the name used by only a
very few scientists and the name used by most
researchers “Qing hao su”, had a certain exotic and
lyrical ring to it that caught everyone’s attention. Not
only its name, but also the remarkable promise of the
activity of this new compound captured people’s attention
like few other compounds had done in many, many
years. The WRAIR always had teams looking for new
leads in the field and the WRAIR teams quickly learned
of the evolving miracle from the Far East. Dr. Wilbur
Milhous, considered by many at the WRAIR as the “village
elder” for the Division of Experimental
Therapeutics, recalls, “It was 1982 and I was a fellow
at Burroughs Wellcome. We received a report from the
WHO (World Health Organization) malaria steering
group in Geneva saying there was a promising new
Chinese plant called qing hao.” Rumors of a miraculous
new Chinese cure for malaria had been circulating
for years in the very small circle of ‘science geeks’ who
specialized in the search for new chemotherapeutic
Correspondence: Peter J. Weina
PhD, MD, FACP Colonel, Medical Corps, USA
Walter Reed Army Institute of Research
503 Robert Grant Avenue
Silver Spring, Maryland 20910
Tel: 301-319-9956; fax: 301-319-7360,
e-mail: peter.weina@amedd.army.mil
drugs for malaria at the time. The Chinese had first
published their findings in the Chinese Medical Journal
in 1979, but being in Chinese and having limited distribution
before the days of the internet explosion, only a
few people outside of China knew of their work. When
discovered by scientists at the WHO, Chinese scientists
were approached for samples of the plant so they could
conduct their own assays, but they were rebuffed.
Clearly in retrospect, it can appreciated that as this was
just after the Nixon era and Mao Tse-tung was still in
power, the Chinese were very skeptical about sharing
information with the outside world. Their greatest fear
was that it would be utilized by large western commercial
pharmaceutical companies for monetary gain.
Ironically, qing hao had been known to Chinese herbalists
for more than 2,000 years. Although there is some
confusion regarding the difference between Artemisia
annua L. and A. apaicea, known in the 1 st century BC
as cao hao (or herbaceous hao) and in the 2 nd century
BC as qing hao (or blue-green hao), both were in common
use in Chinese herbal medicine and both contain
the antimalarial substance artemisinin. Elisabeth Hsu
in the Transactions of the Royal Society of Tropical
Medicine and Hygiene describes and dissects the sometimes
confusing differentiation between the two plants
and their use in the Chinese materia medica. This relatively
common weed found in many parts of the world
is better known to gardeners by its common name,
sweet wormwood. Like cinchona, and many other
members of the Compositae family to which it is related
(sagebrush, tarragon, absinth), sweet wormwood is
particularly noted and prized for its aromatic bitterness.
For as long as this herb has been known and used
though, its soon to be central role in antimalarial usage
was only truly appreciated at the height of the Cultural
Revolution when Mao ordered his scientists to solve
the problem of malaria that was spreading through
China’s southern provinces and ravishing the
Vietnamese military. Even though well known to people
like Ge Hong, who in the 4 th century was the first to
write about recommending the drug qing hao for the