DRUG DEVELOPMENT TRENDS
and Koch’s subsequent work, Rosen suggests their most important
contributions to science involved their establishment of dedicated
research laboratories and rigorous investigational techniques.
Rosen presents extensive details of the day-day work done
by Paul Ehrlich and his collaborators as they pursued his“magic
bullet” theory of disease and discovered the antibiotic Salvarsan.
He adds a bit of perspective on that work by also acknowledging the achievements of men such as Lavoisier, Dalton, Kekule,
and Thomson. Indeed, at the turn of the nineteenth century, the
combined efforts of researchers in many countries led to an explosion of knowledge in the relatively new science of chemistry.
Rosen suggests that the earliest physicists, mathematicians, and
biologists would be somewhat familiar with parts of a modern
textbook on their subject. But a medieval alchemist or apothecary
would find his knowledge to be quite out-of-date.
In yet another interesting perspective, Rosen notes how the
exciting promise of advances in pharmaceutical chemistry that
occurred right up until the introduction of an improved version
of Salvarsan (called Neosalvarsan) in 1912 was short-circuited by
the global conflagration that impeded such research beginning in
August 1914. He picks up the story with the post-war achievements of German chemists who finally discovered that the combination of an azo dye and a sulfanilamide side chain was able to
kill the family of Streptococci bacteria. As also noted in The Drug
Hunters, this became Bayer’s Prontosil in 1935.
This version of that story provides more details about the discovery of sulfanilamide as the drug’s active ingredient and the
implications of that fact for the economics of pharmaceutical
sales and marketing. It also covers the tragedy of S.E. Massen-gil’s Elixer Sulfanimide and the passage of a new Federal Food,
Drug, and Cosmetic Act in 1938. Rosen also notes yet another
problem with the family of related sulfa drugs—the evolution of
antibiotic-resistant bacteria that limited the utility of what had
once seemed like a group of truly miracle products.
Miracle Cure provides a more thorough explanation than The
Drug Hunters of the discovery of penicillin, starting with the Alexander Fleming’s initial encounter with Penicillium notatum in 1927
and ending with the identification of the seventeen companies
chosen to manufacture commercial quantities of penicillin in 1943.
Rosen uses that part of the story as a jumping-off point to describe
the emergence in the post-World War II years of a more professional pharmaceutical industry. Companies such as Abbott Laboratories, Eli Lilly, Merck, and E.R. Squibb and Sons had long been
making purified commercial quantities of various drugs and devoting some dollars to research on new products. They and others in
the United Kingdom and Europe now began investing millions of
dollars in state-of-the art research and production facilities.
Selman Waksman, Albert Schatz, Corwin Hinshaw, and Rob-
ert Woodward deserve to be just as well known as Alexander
Fleming. In the late 1940s and early 1950s their efforts led to the
development of Streptomycin, Aureomycin, Terramycin, Tetracy-
cline, Erythromycin and other wonder drugs capable of attacking
a range of bacteria-causing diseases. The story takes an unex-
pected twist, however, as Rosen notes how questionable patents,
indistinct therapeutic effects, various cross-licensing agreements,
and emerging drug-specific resistance dampened the financial
prospects of many products. He tells how the efforts of Austin
Bradford Hill and Arthur Sackler helped bring clarity to the use of
these new drugs. Hill was a researcher who recognized the value
of randomized, controlled clinical trials long before the FDA be-
gan requiring them in 1962. Sackler was the first of a new army
of advertising and marketing executives whose creative and per-
sistent campaigns convinced physicians to prescribe their com-
panies’ proprietary, branded products. Prior to the discovery of
penicillin, 75% of all prescriptions were compounded by phar-
macists using physician-supplied instructions; by 1955, 90% of all
prescriptions were for branded products.
As had frequently happened before, the hubris of the drug
industry was about to be challenged. One of the miracle antibiot-
ics, Parke-Davis’ Chloromycetin, was found to cause more cases
of aplastic anemia than occurred in the general population. The
incidence was“only”1 in 40,000 patients. But it was a side effect
that was not particularly emphasized by the detail men selling
this very profitable product to the physician community. Trust-
ing those companies to provide complete information about their
products seemed unwise. At the time, neither the FDA nor any
other government agency had the power to force them to con-
duct rigorous studies to thoroughly validate each new product’s
safety and efficacy before putting it on the market. But individual
reviewers such as Dr. Frances Kelsey still had the authority to
question companies about their potential new products before
approving them for sale.
Rosen only provides the briefest comments on Dr. Kelsey’s
success in limiting in the United States the number of birth de-
fects associated with the use of Richardson-Merrell’s thalidomide.
He does note, however, how that tragedy prompted Congress to
expand the FDA’s power to require extensive documentation of
any potential new product’s safety and effectiveness. He ends
his history by commenting briefly on the decline of antibiotic re-
search in the twenty-first century, while also acknowledging the
recent initiation of the HWPAR and GAIN programs aimed at
correcting that mistake. (Some 60% of all hospital-acquired in-
fections are resistant to treatment with the current group of anti-
biotics.) Rosen’s plea for a renewed attack on the world’s species
of bacteria came too late to save his own life; he passed away
from gastrointestinal stromal cancer in April 2016, about a year
before his book hit the shelves.
Reading The Drug Hunters and Miracle Cure will not help answer the key question of the actual cost of developing a successful new drug. Indeed, the former’s first chapter cites the $1.5 billion figure published in 2014 by the Tufts Center for the Study of
Drug Development (CSDD); the latter’s Epilogue cites the figure
of $43.4 million as reported in 2011 in the journal BioSocieties.
Regardless, both works provide chapter and verse of the struggles encountered by drug researchers across time as they have
sometimes succeeded but more often have failed to used their
knowledge and skills to unlock the mysteries of human disease
and treatment. CP
MICHAEL A. MARTORELLI is a Director Emeritus at the investment banking firm Fairmount Partners. For additional commentary on the topics covered in this article contact him at