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Designs that Enrich LivesArchiv der Pharmazie 102007.

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Arch. Pharm. Chem. Life Sci. 2007, 340, 509 – 510
R. Byrne et al.
509
Designs that Enrich Lives
A. Link (Greifswald, Germany)
H. Stark (Frankfurt, Germany)
Clear motivation
The ancient New World seemed to be a relatively healthy environment until small-pox,
malaria, and yellow fever of Old World origins arrived, imported unwittingly by Europeans. In fact, many human diseases are believed to have originated in the Old World
in parallel to increasing population and the close contact to livestock associated with
the rise of agriculture.
According to a recent review by Wolfe, Dunavan, and Diamond (Nature 2007, 447,
279 – 283), the number of major human diseases divided by the number of animal
species in the taxonomic group contributing those diseases, is approximately 0.2 for
apes, 0.017 for non-human primates other than apes, 0.003 for mammals other than
primates, 0.00006 for vertebrates other than mammals, and either 0 or else
0.000003 (if cholera really came from aquatic invertebrates) for animals other than
vertebrates.
Thus, it might have been wise of our ancestors to avoid contact with Old World apes
and live in small groups in order to spare their offspring the many health burdens we
are faced with today. As there is no second chance to rediscover a comparable paradise
like the New World, this unique chance in history was lost forever. The rise of new infectious agents in our growing world population, which has been going on over the last
10 000 years, is expected to continue. This scenario is one reason among many why
there is a persistent need for modern societies to be continually developing novel therapeutics. The pharmaceutical industry has met this task splendidly during the 20th century, mainly by developing small molecule drugs. This is widely and justly seen as an
important factor for the high standard of living in developed countries.
Uncertain reward
While the ethical reward for drug discovery is undisputed, the financial reimbursement
is being questioned. Price-control policies in force in most nations of the European
Union strictly limit the amount of money that can be earned with the development of
new drugs. On top of that, owing to continuing public discontent about continually
increasing healthcare costs, there is the possibility of a major healthcare reform after
the 2008 presidential election in the United States, which may lead to a similar situation for the world's most important market.
Today, many patents on block busters are beginning to expire – within the next 5
years, drugs worth more than 40 billion a in sales will go off patent. Recent withdrawals
of some high-profile therapeutics due to safety concerns have forced pharmaceutical
companies to strive to replenish dried-up, late-stage pipelines at the same time keeping
costs down. Thus, the exhilarating growth that the pharmaceutical sector enjoyed in
the 1990s is not likely to be revisited in the next decades, leading many companies to
look for growth in the closely related sector of biotechnology.
Biotechology: The sharper image?
The obvious fact that drugs have to be sold for profit to compensate the costs and risks
of drug discovery programs, and the striking observation that marketing efforts are
sometimes as expensive as research and development, nourishes a negative public
image of this industry. In fact, the public’s view of the “pharma” industry is sometimes
worse than that of ”tobacco” industry. Therefore, it has become a trend for pharmaceutical companies to align their public image more closely with that of their biotechnology components, which are generally believed to be particularly innovative, science-
i
2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
510
Designs that Enrich Lives
Arch. Pharm. Chem. Life Sci. 2007, 340, 509 – 510
based, and more responsive to patient needs. This will probably only be a short-term cure
because biotechnological drugs will be marketed in the same way as traditional drugs
have been marketed in the past.
The negative comment that is often heard, and is probably true, is that pharmaceutical
companies develop drugs for rich people and not for the billions of people living on less
than 2 a a day. Nevertheless, the world’s cleverest industrial designers are also creating
items like fancy golf clubs and noble cars for the globe's richest, while ignoring the masses
that are in need of simple water pumps or ingenious, inexpensive transport devices.
Old strategies expired?
In terms of science and innovation, the future for small-molecule drugs looks bright. The
often quoted sequencing of the human genome and parallel developments in Immunology and Cell Biology will not only lead to the development of novel antibodies but will
help in developing effective therapeutics through de-novo design, screening of synthetic
compound libraries or from natural product leads, maybe even drugs matched to an individual patients' genotype or phenotype.
Until recently, safe, small-molecule drug candidates that failed in clinical trials in terms
of efficacy were put on ice as drug developers redirected resources to the next candidates.
Nowadays, in an effort to trim costs, technologies making use of the improved genomic
information and new high-throughput screening methods make it possible to quickly and
economically re-evaluate such safe, advanced drug candidates as drugs against related or
even unrelated diseases. This possibility of turning failed drug candidates from one therapeutic area into successful treatments in another is an underexplored asset of small molecules, which are notoriously prone to multiple interactions in the human body.
Therefore, the near future will hopefully see many novel or recycled chemical entities as
cures for important human diseases as well as economic success stories for the pharmaceutical industry. The Old-World journal Archiv der Pharmazie – Chemistry in Life Sciences, one of
the oldest journals in Medicinal Chemistry, will report on the complicated process of refilling the dwindling pipelines by publishing mini-reviews on compounds in clinical development in this and some of the next volumes. These monographs on clinical candidates are
intended to critically review the facts to discriminate between quality information and
wrong or unclear data in emerging therapeutic fields. Furthermore, they are intended to
enable the reader to get an early glimpse at ongoing research in Medicinal Chemistry,
long before the results reach the textbooks. Finally, these monographs will help the reader
navigate his/her way through the web-based information overkill.
Printed books in a store appear monolithic while many interesting pages are missing in
the final manuscript because they ended up in a paper basket beneath the author's desk.
Likewise, in a drug-discovery program many interesting experiments are not followed up
on because the project dictated other priorities, but they are nevertheless of high academic
value or a source for new inspiration for other scientists. The editors invite researchers
from the pharmaceutical industry to share their results with scientists from academia and
vice versa. In particular, Prof. Dr. Andreas Link, Greifswald, Germany, as new Senior Editor
for Archiv der Pharmazie – Chemistry in Life Sciences, will put this on his list of priorities to
publish topical contributions to areas of drug research that have been underestimated so
far.
A. Link, Greifswald, Germany
i
2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
H. Stark, Frankfurt, Germany
www.archpharm.com
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