Conservation and Sustainable Use of the Biosphere - WBGU

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Conservation and Sustainable Use of the Biosphere - WBGU

66 D The use of genetic and species diversity

100,000 synthetic substances have to be tested to

bring a new medicine onto the market, the same

number of randomly collected plants is sufficient to

develop on average five new medicines. The success

rate of ethno-botany is probably even higher, for

here the effect of traditional medicinal plants is

already proven (SAG, 1997).

In contrast to the long development story of

Aspirin ® (Box D 3.3-2) the development of Taxol ®

represents the modern bioprospecting approach

(Box D 3.3-3). In the case of Taxol ® a horizontal

genetic exchange, probably with a fungus in the bark

of the yew tree, means that in future Taxol ® does not

have to be produced from yew plantations but can be

produced from cultures of this fungus. By identifying

the gene for the substance of interest, eg through

modern molecular diagnosis (eg differential display)

and highly effective sequencing techniques, even

more prospects open up. As will be explained with

examples in Section D 3.3.4, the desired gene can be

transferred (‘transfected’) into a cultivated plant, but

also in an easily cultivatable microorganism. With

this type of measure, economic viability can often be

enhanced.

D 3.3.3.3

Terrestrial microorganisms

Terrestrial bacteria and fungi are predestined as producers

of secondary metabolites as generally they

live in symbiotic or parasitic relationships. As illustrated

by the example of Taxol ® , increasingly

microorganisms are being identified as the real

source of substances which originally were wrongly

ascribed to a parasitized plant (or animal) or one living

in symbiosis.The poisonous ergot of rye alkaloids

that are produced by sac fungi living on cereals

(Ascomycetes of the Claviceps genus) are a classic

example. Accordingly, the interest in bioprospecting

microorganisms is growing, particularly since so far

only a fraction of these have been identified and

analysed (Table D 1.2-1).

Consequently, some 50 per cent of individual projects

supported under the BMBF’s support focus

‘Biotechnology 2000’ address the use of microorganisms

and their products. A large number of highly

effective antibiotic, cytostatic (cell-growth inhibitors)

or immune-suppressant substances from various

microorganisms have been used for years. Over

20 different antibiotics are produced from Streptomyces

species alone. This family also produces a

larger number of cancer blocking cytostatica and

Box D 3.3-2

Aspirin ® – a one-hundred year history

Back around 400 BC Hippocrates was prescribing an infusion

from the bark of the white willow (Salix alba) against

inflammation of the joints. The proponents of the signature

theory in the Middle Ages used white willow tea to treat

stiff joints and rheumatic pain because the willow had supple

branches. The natural painkiller was forgotten for a

while until in 1763, a Mr Stone from England described the

anti-pyretic effects of willow bark. This finding was used in

1806 at the time of the Continental Blockade in Germany as

an urgently needed substitute for China bark (Chinchona)

that could no longer be imported.The following steps led to

the manufacture of pure acetylsalicylic acid, the active substance

in willow bark:

• in 1828 J A Buchner isolated a yellowish mass from willow

bark, that he named Salicin.

• in 1829 the French apothecary Leroux isolated Salicin in

crystallized form.

• in 1838 R Piria manufactured salicylic acid from Salicin.

At around the same time the Swiss apothecary Pagenstecher

distilled salicylaldehyde from the flowers of the

herbaceous meadow-sweet (Filipendula ulmaria; syn.

Spiraea ulmaria); oxidation to salicylic acid followed.

• in 1853 the chemist C F Gerhardt managed for the first

time to synthesize an impure, but also non durable,

acetylsalicylic acid.

• in 1874, after H Kolbe had elucidated the chemical structure

of salicylic acid, industrial production began.

• in 1876 Ries and Stricker proved that the synthetic salicylic

acid was suited to treating rheumatic fever and it

cost ten times less than the natural substance.

The chemical factory of Friedrich von Heyden (Radebeul-

Dresden) and the Elberfeld paint factory, previously

Friedrich Bayer & Co., tried to develop a variety that would

be tolerable to the stomach. In August 1897 the chemist Dr

Felix Hoffmann (Friedrich Bayer & Compagnon) reported

for the first time a chemically pure and durable acetylsalicylic

acid (ASA) extracted by acetylisation. The preparation

was registered under the name Aspirin ® and patented

in 1899.The First World War, with its immense need for pain

and fever medication, the renewed and now total import

blockade on quinine and finally the great fever pandemic of

1918/19 all promoted the success of Aspirin ® . The British

pharmacologist John R Vane received the Nobel prize for

medicine in 1982 for elucidating the active mechanism of

ASA. Currently, new forms of ASA with longer effect and

reduced side effects are being developed, such as Celebrex ®

and Vioxx ® ; they were approved for the US market in 1999.

ASA is constantly being ascribed new indications, eg lowering

the risk of heart attack or reducing the risk for certain

types of cancer. Bayer AG took a long time to correctly

place Aspirin ® in the market which for a long time now has

not been under patent protection. Today in Bitterfeld 785

tonnes of acetylsalicylic acid is processed annually to produce

Aspirin ® tablets (1.8 million per hour) – that is a third

of total world Aspirin ® production with annual sales of

US$425 million. Aspirin ® is the most frequently sold drug

on all continents.

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