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TECHNOLOGY REVIEW /
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Since 2000, the U.S. Food and
Dr ug Administration has re-
ported a general decrease in
the number of new molecular enti-
ties---drugs with new chemical str uc-
tures---submitted for approval each
year, indicating a decline in the dis-
covery of new drugs. Thirty-six years
ago, pharmaceutical professionals also
wor ried about dr ug discovery and la-
mented a decline in the rate at which
new drugs were reaching the U.S.
market. In December 1970, Technol-
ogy Review published "Dr ugs: Has
the Age of Miracles Passed?...and
Will That of Science Ever Dawn?" It
was a two-part review of a sympo-
sium on dr ug discovery at the Amer-
ican Chemical Society s national
meeting that year. Barry M. Bloom, a
representative from P zer, presented
data, summarized in the bar graph
shown here, demonstrating a decline
in the rate of drug discovery.
In 1962 the Food, Drug and Cos-
metic Act was amended to require
that any new drug should be not only
safe but efficacious. Since 1962, Mr.
Bloom finds, there has been a marked
tendency for new drugs to be either
antibiotics, cancer treatments, or neu-
ral agents, to the neglect of the general
run of diseases. In his view, discov-
ery goes on very much as it used to,
but the only drugs that reach the U.S.
market are those for which an efficacy
demonstration is relatively easy.
The section concludes that it now
costs about six times as much to dis-
cover a new drug, saleable in the U.S.,
as it did ten years ago. (Francis J. Blee,
of Drexel Harriman
produced the following
figures: research and
ment per "new entity"
between 1956 and
between 1963 and 1969,
$23.1 million.) There is
therefore a keen inter-
est in the question of which methods of
finding drugs are likely to work.
Of equal concern is how these
drugs function within the human
body. In this month s Q&A (see p. 36),
Har vard University computational
biologist George Church discusses
the impact of scienti c breakthroughs
such as high-throughput gene sequenc-
ing on our understanding of biologi-
cal systems. Church believes the day
is near when dr ugs will be engineered
to recognize tumors and individu-
als can a ordably have their genomes
sequenced, revolutionizing personal
medical treatment. In the second part
of the 1970 article, scientists dreamed
of such increased knowledge of biol-
ogy and the potential impact on dr ug
discovery while recognizing the gaps
in their era s science.
Finding new drugs is a form of
professional gambling: some people
think they have a system. William P.
Purcell of the University of Tennessee
holds that "from a philosophical point
of view, one can reason that if we
have the resources, such as manpower,
knowledge, sophisticated instrumen-
tation, computers, etc., to bring a
successful moon walk to fruition,
one would anticipate that a molecule
could be tailor made to be effective
against a specific disease."
Dr. Purcell is for designing drugs
for specific purposes, applying com-
puters to the correlation of biological
activity with chemical structure. He
admitted, though, that "one knows
more about the molecular structure
of an isolated molecule from instru-
mental analyses than about the spe-
cific interaction of this molecule with
a complicated biological system....
The level of sophistication of handling
simultaneous equations is greater than
the understanding of a parameter
from pharmacological testing."
John J. Burns, of Hoffman-La
Roche, Nutley, N.J., spoke of a related
shortcoming which he called the "bio-
logical knowledge gap": a lack of
basic understanding of disease pro-
cesses and of what drugs actually do.
For finding new drugs, the random
synthesis of compounds, followed by
screening for biological activity, is still
worthwhile, as long as the biologists
are good ones, and as long as they
talk to the chemists.
The Elusive Nature
of Drug Discovery
Understanding how drugs work has never been easy.
By Jessica B. Baker
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