Book ReViews
Journal of Medicinal Chemistry, 2009, Vol. 52, No. 7 2161
Book ReViews Drug Truths. Dispelling the Myths About Pharma R&D. By John L. LaMattina. John Wiley & Sons, Inc., Hoboken, NJ. 2009. xiv + 136 pp. 15.5 × 23.5 cm. ISBN 0470393181. $25.00. According to a 2004 Harris Interactive Survey, only 44% of 979 adults answered that pharmaceutical and drug companies were doing “a good job of serving their consumers” whereas 48% responded that they were doing “a bad job”. An industrial medicinal chemist, aware of the 19 NMEs (new molecular entities) including five first-in-class therapies launched in that year, might well be disappointed by this perception of his or her work. Responding to the apparent disconnect between pharma achievements and public understanding, this book’s author, a former president of Pfizer Global R&D, attempts to dispute publicly accepted “myths about pharma R&D” with alternative “truths”. The volume is divided into 12 chapters in which the author offers defenses (usually based on Pfizer drug discovery experiences) against various criticisms of the industry that include the marketing of “me too drugs”, excessively long discovery timelines, unnecessary pharmaceuticals, “invented diseases”, inattention to developing world diseases, inadequate cost-benefit ratio of new medicines, the perceived greater safety of older established drugs versus newly introduced agents, the comparative value of academic research contributions versus industrial research achievements, the supposed superiority of biotechnology-based drug discovery versus traditional approaches, and the apparent excessive industry advertising expenditures in comparison to R&D investment. Some examples are convincing, such as the broad success of Lipitor, a putative “me too drug” that was the fifth statin to reach the market place. But others are less persuasive; no mention is made of menopause as an “invented disease” that resulted in the hormone replacement therapy (HRT) fiasco, now believed to account for a substantial increase in the incidence of breast cancer among women who undertook HRT. The real problem that faces the industry has been defined by Pharmaceutical Research and Manufacturers of America (PhRMA) President and CEOI Billy Tauzin as “trust”. Exemplary of such trust issues, the Wall Street Journal in January reported separate agreements by GlaxoSmithKline, Lilly, and Pfizer to pay amounts ranging from $400 million to $2.3 billion in settlement of improper marketing charges, including “off-label” promotion for indications not approved by the FDA. Likewise, a 2006 PriceWaterhouseCooper Health Research Institute survey revealed that fully 94% of consumers agreed that drug companies can be too aggressive in promoting unapproved uses of their products; only 10% agreed that Direct to Consumer (DTC) advertising provides complete and useful information to them, and only 50% agreed that drug companies have sufficient programs in place to monitor the postmarket safety profile and public health risks of their products. Although this book laudably attempts to address these consumer concerns, it is a mischaracterization to refer to them as “myths”; the large sums agreed to by some of America’s largest pharma in settlement of improper marketing charges indicate a basis in reality. Moreover, to base the “truths” so heavily on the experiences of a single company weakens their generality. By contrast, if properly carried out, policies such as those recommended by PriceWaterhouseCooper Health Research Institute to “ensure that marketing practices and promotional
activities focus on improving the treatment of diseases as well as... the cost-benefit ratio of treatments, and communications around safety profiles” would likely begin to rebuild “trust” in pharma more effectively. Manfred E. Wolff Intellepharm, Inc. 1304 Morningside DriVe Laguna Beach, California 92651-2809 JM900208Q 10.1021/jm900208q
Pathway Analysis for Drug Discovery. Computational Infrastructure and Applications. Edited by Anton Yuryev. Wiley, Hoboken, NJ. 2008. x + 303 pp. 16 × 24 cm. ISBN 0-470-10705-8. $100.00. In one way or another, much of biology is chemistry. A cell or organism has chemical systems and subsystems that interact with each other to do things. The lines of chemical communication between the myriad systems and subsystems of a living organism constitute a network. A pathway shows how information about a chemical or physical event in a cell or organism flows in space and/or time through the network of possible chemical interactions that can occur. In the context of drug discovery, pathway analysis entails analyzing experimental data, which is often noisy, using specialized computer programs. The goal is to understand the flow of chemical information in normally functioning biological systems and comparing that to the flow when those systems are disrupted by disease. The latter situation is called “malignant information flow.” This book comprises 13 chapters, of which the editor, Anton Yuryev, has authored or coauthored four. About two-thirds of the 26 contributing authors work at small start-up companies. The chapters cover introduction to pathway analysis, software of two of the companies represented by the authors, algorithms for viewing the data, working with high-throughput data, examples from oncology, applications to toxicity data, potential uses in drug discovery, protein-protein interactions, yeast glucose, and prospects for the future. The chapter on algorithms will attract informatics experts. The chapter on the impact of pathway analysis includes interesting tidbits of information that will be of interest to pharmaceutical workers and is well written. Throughout the book, many of the diagrams of pathways look like birds’ nests of overlapping, untraceable gray lines. Even though some of the gray-scale figures are also available in the color plates and on a compact disk that is included with the book, they are still hard to decipher. The figures have a large number of different icons. These are never explained in the book, which leaves the reader to wonder what their significance is. The reader may also want to know what software was used to produce each of the figures. As with most books, the copy editor used by the publisher could have done a little more thorough job in smoothing the English. The seven-page subject index contains many of the acronyms used in the book, but not all of these are defined. Readers who are new to the field could have benefited from having more of these explained. The number of references is consistent with the field being relatively new and specialized.
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Most of the references date from 2003 through 2007. Fewer than 8% of the references predate 2000. A few references are to 2008 publications. The editor does a fine job in introducing the subject matter in Chapter 1 and offering his final perspectives in Chapter 13. He has a penchant for using the first person personal pronoun, and readers of the traditional scientific literature may notice this. The editor writes that the FDA approves one out of 5000 drugs and cites as his source a 2002 editorial by Kevin Davies, Editorin-Chief of BIO-IT (ref 29 on p 296 of the book). Davies wrote a variant of the (precombinatorial chemistry) cliche´ that out of 5000 or 10 000 compounds that are synthesized, one compound will reach the market to treat patients. Of course, only one or two of the most promising compounds, out of the thousands synthesized, are ever submitted for approval by the FDA. The Davies editorial also quotes Fred Hassan (who was CEO of Pharmacia and then led Schering-Plough) as saying “People got way too excited about the [human] genome being unlocked. Five or 10 years from now, it might help our product flow.” Davies added that “Understanding the root cause of disease does not necessarily translate into developing a successful drug.” These two observations are worthy of contemplation. Yuryev argues that pathway analysis will lead to more drug mixtures being used therapeutically to block multiple pathways.
He thinks that drug approval agencies of governments require an absence of toxicity and side effects. While such a goal might be desirable, most agencies realize that, depending on the disease being treated and the availability of other medicines in that therapeutic area, an acceptable level of benefit/risk ratio is all that can be hoped for. The book is mostly written for the situation of a patient with faulty pathways, such as in the case of cancer. But many diseases involve bacterial, fungal, or viral infection, so the disease involves pathways in each organism and feedback between the host and infective agents. Pathway analysis will help lead to a better understanding of the chemistry of living systems and the aberrations that disrupt health. This new book will serve as a beacon to researchers interested in this field. Donald B. Boyd Department of Chemistry and Chemical Biology Indiana UniVersitysPurdue UniVersity at Indianapolis Indianapolis, Indiana 46202 JM900139S 10.1021/jm900139s
