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Driven by chemistry but increasingly guided by pharmacology and the The Impact of New Technology on
clinical sciences, drug research has contributed more to the progress of Drug Discovery
medicine during the past century than any other scientific factor. The During the first half of the 20th century drug
advent of molecular biology and, in particular, of genomic sciences is research was shaped and enriched by several
having a deep impact on drug discovery. Recombinant proteins and new technologies, all of which left their im-
monoclonal antibodies have greatly enriched our therapeutic armamen- print on drug discovery and on therapy. In
tarium. Genome sciences, combined with bioinformatic tools, allow us to 1938, E. Chain, Howard Florey, and their
dissect the genetic basis of multifactorial diseases and to determine the collaborators selected penicillin, a metabolite
most suitable points of attack for future medicines, thereby increasing the from a penicillium mold that could lyse
number of treatment options. The dramatic increase in the complexity of staphylococci, for further study (10). Penicil-
drug research is enforcing changes in the institutional basis of this inter- lin had been discovered in 1929 by Alexander
disciplinary endeavor. The biotech industry is establishing itself as the Fleming (11), and a large number of antibi-
discovery arm of the pharmaceutical industry. In bridging the gap between otic substances had been described in the
academia and large pharmaceutical companies, the biotech firms have scientific literature between 1877 and 1939.
been effective instruments of technology transfer. Chain and Floreys choice turned out to be
very fortunate. Because of its efficacy and
The Evolution of Drug Discovery tury led to unprecedented therapeutic tri- lack of toxicity, penicillin made the most
As an interdisciplinary endeavor with an umphs (4 ). compelling case for antibiotics in general. It
industrial base, drug research is not much Analytical chemistry, in particular the iso- opened the door to a new era in the treatment
older than a century. Drug research, as we lation and purification of the active ingredi- of bacterial infections. After the discovery of
know it today, began its career when chem- ents of medicinal plants, also demonstrated penicillin and subsequently of other antibiot-
istry had reached a degree of maturity that its value for medicine in the 19th century. In ics, many drug companies established depart-
allowed its principles and methods to be 1815, F. W. Serturner isolated morphine from ments of microbiology and fermentation
applied to problems outside of chemistry opium extract (5). Papaverin was isolated in units, which added to their technological
itself and when pharmacology had become 1848, but its antispasmodic properties were scope. There were only a few large compa-
a well-defined scientific discipline in its not discovered until 1917 (6). As active in- nies that did not participate in the search for
own right (1). By 1870, some of the essen- gredients from plants became available, many new antibiotics. Some companies, for exam-
tial foundations of chemical theory had pharmacies addressed the problem of provid- ple Merck, Sandoz, and Takeda, used their
been laid. Avogadros atomic hypothesis ing standardized preparations of these often microbiological capabilities to find drugs that
had been confirmed and a periodic table of still impure drugs. exerted other pharmacological or chemother-
elements established. Chemistry had devel- Coal-tar, an abundant by-product of the apeutic properties: Ivermectin, a superior drug
oped a theory that allowed it to organize the industrialization, contained many of the ar- against tropical filariosis; lovastatin, a HMGA-
elements according to their atomic weight and omatic or aliphatic building blocks that Co reductase inhibitor; and the immuno-
valence. There was also a theory of acids and became the toolkit of medicinal chemistry
bases. In 1865, August Kekule formulated his from its beginnings to the present (7 ). Fi-
pioneering theory on the structure of aromatic nally, pharmacology, which had its roots in
organic molecules (2, 3). the physiological experiments of Francois
This benzene theory gave a decisive Magendie and Claude Bernard, claimed its
impulse to research on coal-tar derivatives, place among the medical disciplines. Under
particularly dyes. In turn, the evolution of the leadership of Oswald Schmiedeberg, the
dye chemistry had a profound influence on institute of pharmacology at the University of
medicine. The selective affinity of dyes for Strasbourg laid many of the intellectual and
biological tissues led Paul Ehrlich (Fig. 1), experimental foundations of pharmacology
a medical student in the laboratory of the between 1871 and 1918 (8). However, none
anatomist Wilhelm Waldeyer (between of the institutions that had supported these
1872 and 1874) at the University of Stras- seminal effortspharmacies, university lab-
bourg, to postulate the existence of che- oratories, or the chemical companies produc-
moreceptors. Ehrlich later argued that cer- ing dyesrepresented suitable platforms for
tain chemoreceptors on parasites, microor- the newly emerging drug research that was
ganisms, and cancer cells would be differ- driven by chemistry but increasingly con-
ent from analogous structures in host trolled by pharmacology and by clinical sci-
tissues, and that these differences could be ences. New institutions to support interdisci-
exploited therapeutically. It was the birth of plinary drug research and development had to
chemotherapy, a particular type of drug be created. They either grew out of pharma-
therapy, that in the course of the 20th cen- cies or were founded as pharmaceutical divi-
sions in chemical or dye companies. A new Fig. 1. Paul Ehrlich, who was the first to argue
International Biomedicine Management Partners,
way of finding, characterizing, and develop- that differences in chemoreceptors between
Basel, Switzerland and Orbimed Advisors LLC, New ing medicines led to the formation of a new species may be exploited therapeutically. [Im-
York, NY 100172023, USA. industry (9). age: National Library of Medicine]
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