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Magic Bullets and Wonder Pills:
Making Drugs and Diseases in the Twentieth Century
BY B R U N O J . S T R A S S E R ∗
Robert Bud. Penicillin: Triumph and Tragedy. Oxford: Oxford UniversityPress, 2007. 344 pp., illus. ISBN 978-0-19-925406-4. $46 (hardcover).
Jeremy A. Greene. Prescribing by Numbers: Drugs and the Definition ofDisease. Baltimore: Johns Hopkins University Press, 2007. 336 pp., illus. ISBN978-0-8018-8477. $42.70 (hardcover).
John E. Lesch. The First Miracle Drugs: How the Sulfa Drugs TransformedMedicine. Oxford: Oxford University Press, 2007. 376 pp., illus. ISBN 978-0-19-518775-5. $59.50 (hardcover).
Elizabeth Siegel Watkins. The Estrogen Elixir: A History of HormoneReplacement Therapy in America. Baltimore: Johns Hopkins University Press,2007. 368 pp. ISBN 978-0-8018-8602-7. $37.10 (hardcover).
In 2007 the pharmaceutical industry struggled to bring new drugs onto the market. For historians of science and medicine it was a much more rewardingyear. An unprecedented number of new books on the history of drugs have ap-peared, and more are in the pipeline. Even though the profits of scholarshipare undoubtedly more modest, these histories greatly enrich our understand-ing of current debates on declining returns on investments in pharmaceuticalinnovation, rising costs of drugs in health care, and the broadening of patho-logical categories. They also illuminate how and why drugs have become an *Section of the History of Medicine, Yale University, New Haven, CT 06520; bruno.
Historical Studies in the Natural Sciences, Vol. 38, Number 2, pps. 303–312. ISSN 1939-1811, electronicISSN 1939-182X. 2008 by the Regents of the University of California. All rights reserved. Pleasedirect all requests for permission to photocopy or reproduce article content through the Universityof California Press’s Rights and Permissions website, http://www.ucpressjournals.com/reprintinfo.
asp. DOI: 10.1525/hsns.2008.38.2.303.
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essential part of our cultural diet. Finally, these new histories of drugs showvividly how the historiography of science and medicine can encompass the re-lationships among the laboratory, the clinic, the factory, and the marketplacein the production of knowledge.
But what exactly is a “history of a drug” a history of? The most common an- swer—that it is a history of the drug’s active molecule—has proved to be a mis-leading simplification. The standard narrative of the “magic bullet” has almostexclusively followed a single pattern: A (usually lonely male) laboratory scientist,in search of a molecule that could cure a (usually deadly) disease, stumbles (usu-ally accidentally) on a specific substance that is effective against that specific dis-ease. The long and complex path from the scientist’s test tube to the patient’spillbox is conspicuously absent from the story. The basic structure of the narra-tive, mainly produced by academic scientists and historians of the experimentalsciences and medicine, should not invite ridicule. Indeed, it reflects essential tenetsof the “magic bullet ideology” that, by placing the laboratory at center stage,played a crucial role in reconfiguring drug development during the first part ofthe twentieth century. Today the promise of the “magic bullet” looks less certainand the future of drug development somewhat more gloomy. Current histori-ography brings a new perspective on the ideology and offers more powerful in-tellectual tools to explore the process.
Unlike the standard narrative, the current historiography takes drugs to be more complex entities. They are more than molecules: they are evolving cul-tural productions, carrying many layers of meaning and embedded in multi-ple social networks.1 New histories of drugs feature not only laboratory sci-entists, but also individual medical practitioners and clinicians, engineers andinvestors, sales representatives and pharmacists, and even patients. To put itdifferently, drugs are seen as products of the laboratory, the clinic, the factory,the marketplace, the law, and the media. The idea of a “drug trajectory” or“drug biography” has proven to be a powerful heuristic.2 A biography of adrug that focused solely on its discovery would be as shallow as a biographyof a person concerned exclusively with the conditions of his or her birth. Twomasterly works under review (Lesch and Bud), one about the sulfa drugs and 1. See, for example, Andrea Tone and Elizabeth Siegel Watkins, eds., Medicating Modern America: Prescription Drugs in History (New York: NYU Press, 2007).
2. See Jean-Paul Gaudillière, “Introduction: Drug Trajectories,” Studies in History and Philos- ophy of Biological and Biomedical Sciences 36 (2005): 603-11; Sjaak van der Geest, Susan ReynoldsWhyte, and Anita Hardon, “The Anthropology of Pharmaceuticals: A Biographical Approach,”Annual Review of Anthropology 25 (1996): 153–78.
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the other antibiotics, exemplify this new perspective and the new insights itcan foster.
No drug biography has been told more often the 1929 discovery of penicillin by Alexander Fleming and its subsequent mass production during the SecondWorld War. More than two dozen monographs have focused on this “success”story, and the debate continues over Fleming’s apparent decade-long neglectof the therapeutic potential of the penicillin substance. Robert Bud, a histo-rian at the Science Museum in London and the author of a book on the his-tory of biotechnology considered broadly as the use of life for industrial pro-duction, is particularly well equipped to make a contribution to this overworkedtopic. The originality of his approach in Penicillin: Triumph and Tragedy lies inhis treatment of penicillin “as both a brand and a family of chemicals.”3 Evenbefore covering, in a single chapter and standard fashion, the familiar story ofAlexander Fleming, Ernest B. Chain, and Howard W. Florey, Bud describesthe high hopes for wonder drugs that briefly crystallized in the first half of thetwentieth century around Paul Ehrlich’s Salvarsan, the sulfa drugs, and vita-mins. Penicillin, becoming widely available at the end of the war, met great ex-pectations not only for wonder drugs, but more generally for products that,after wartime hardships, would bring a better life. It was thus ideally suited tobecome a cultural icon of postwar modernity, or, in Bud’s terminology, a “brand.”He tells a fascinating story of how penicillin was “branded” by physicians, sci-entists, governments, the military, and the media, through independent prop-aganda efforts highlighting the benefits for society of modern science, indus-try, and government intervention. Even though Bud focuses on Britain and theUnited States, he also explores, in a very welcome chapter, the production ofpenicillin in other European countries and in China. Where Bud’s perspective on brands proves most useful is in addressing the extraordinary diffusion of penicillin in postwar consumer culture. Framed asa brand, penicillin thrived as a commodity in the marketplace. It had a pro-found cultural impact. For example, it shifted patients’ attitudes toward ther-apeutic intervention, in that they increasingly considered the physician a pre-scriber of antibiotics, rather than a skilled practitioner of the arts of diagnosisand healing. The formidable consumption of penicillin (and other antibiotics),together with its use in large-scale animal husbandry, ironically paved the wayfor the brand’s own demise. Although antibiotic resistance had been debatedsince penicillin was first used, the controversy reached a new intensity in the 3. Robert Bud, Penicillin: Triumph and Tragedy (Oxford: Oxford University Press, 2007), 2.
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1970s and 1980s. Bud suggests that in the wake of the AIDS and BSE epi-demics—neither of which is bacterial and hence neither of which can be treatedby antibiotics—debates about drug resistance made ever more plausible theprospect of a world without antibiotics, the effect of the drug’s very success inthe marketplace. Penicillin’s image as a wonder drug began to fade, even thoughthe consumption of antibiotics had become so entrenched in consumer prac-tices that it continued almost unaffected.
Bud has provided a powerful social and cultural history of the paradigmatic postwar wonder drug, illuminating current debates on drug resistance. As inmost accounts of penicillin, however, there remains a blind spot in Bud’s storytoward clinical trails, fostering the illusion that drugs move smoothly from thelaboratory to the market. In his account the pharmaceutical industries pro-ducing penicillin also remain something of a black box. By drawing on the lit-erature on particular pharmaceutical companies, the author could have clari-fied how penicillin fit into both their research and production traditions. Indeed,the extraordinary diffusion of penicillin was predicated upon industry’s abil-ity to provide it in mass quantities. This goal attracted several companies in theimmediate postwar period, but their success was often forestalled by their lackof experience and expertise in biological modes of production. The First Miracle Drugs: How the Sulfa Drugs Transformed Medicine addressesthese issues only touched upon in Penicillin: Triumph and Tragedy, resulting inwhat is perhaps the most accomplished drug biography to date. John Lesch’sprevious books, histories of experimental physiology in France in the nine-teenth century and of the German chemical industry in the twentieth century,constitute a crucial background to his new history of the sulfa drugs.4 As RobertBud briefly acknowledges, penicillin was not the first miracle drug: it was pre-ceded by the sulfa drugs, and even earlier by Salvarsan. But the sulfas weremuch more than a miracle drug. They inaugurated, as Lesch argues, a new “sys-tem of invention” within industry that is still in operation today. The authorexplores how the German chemical company I.G. Farben, under the guidanceof its research manager Heinrich Hörlein, developed this innovation system inwhich families of chemical molecules would be screened in vitro, and, moreimportantly, in vivo in model animals, for therapeutic activity against a number 4. John E. Lesch, ed., The German Chemical Industry in the Twentieth Century: Chemists and Chemistry (Dordrecht: Kluwer Academic, 2000); John E. Lesch, Science and Medicine in France:The Emergence of Experimental Physiology, 1790–1855 (Cambridge, MA: Harvard University Press,1984).
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of different diseases. Even though Lesch focuses on Germany, he also exploresin detail how the French and British industries followed radically different pathsto develop new sulfa drugs. With the rise of National Socialism, Hörlein’s project was imperiled by the Nazis’ anti-Jewish laws and their endorsement of anti-vivisectionist movements.
However, through a politics of accommodation with the regime, Hörlein suc-ceeded in developing his system by bringing together I. G. Farben’s traditionalexpertise in dye chemistry, its large-scale research facilities, and several inno-vative researchers, including the physician Gerhardt Domagk. Domagk’s abil-ity to see beyond disappointing in vitro trials and his reliance on animal mod-els were key to the 1932 discovery of a powerful antibacterial sulfa compound,which was first marketed under the name Prontosil. This discovery earned Do-magk the Nobel Prize in Physiology or Medicine in 1939. Prontosil did not become a wonder drug overnight. Lesch shows in great detail how the specific uses of the different sulfa drugs were defined just before,and especially during, the Second World War. Here Lesch accomplishes morethan he claims in his introduction, providing a unique exploration of day-to-day therapeutic implementation. Unlike most authors, he does not take thedrug’s efficacy as given, but as a question to be addressed. Even though clini-cal trials had concluded that the sulfa drugs were inefficient for treating woundinfections, they were widely used for that purpose on the battlefront between1943 and 1945. Trial under fire defined a different standard of efficacy than hadclinical trials. After the war, the sulfa drugs were displaced in the news by peni-cillin and other antibiotics, even though the sulfas continue to be used today.
But the sulfa drugs had other and perhaps more important legacies for the de-velopment of pharmaceuticals, namely, a powerful model of industrial inno-vation and the kindling of a persistent hope that chemistry and industrialresearch would produce other wonder drugs.
Lesch’s exploration of this system of innovation could have benefited from a comparison with the methods of Paul Ehrlich and the chemical dye manu-facturer Farbwerke Hoechst AG two decades earlier, which led to the develop-ment of Salvarsan, one of the first syphilis drugs. Indeed, in many ways, thescreening approach of Hörlein seems to have been a translation of Ehrlich’sapproach in a large-scale industrial context. Also, Lesch, like Bud, only givespassing mention to serum (or antitoxin) therapy. Yet serum therapy was one ofthe most popular drug therapies in the first three decades of the century, andits development prefigured many problems encountered with the sulfa drugsand penicillin.
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The only troubling aspect of Lesch’s book is his treatment of Hörlein’s in- volvement with the Nazi regime. As Lesch points out, there is no doubt thatHörlein was not a passionate Nazi supporter, but it is quite a stretch to makehim a victim of unfavorable circumstances, confining him to a strategy of“accommodation and survival.” The fact that Hörlein was supported by AdolfButenandt during the Nuremberg trials should not be taken as conclusiveevidence of his past actions or morals, as Lesch argues it should be. Indeed,Butenandt, we have recently learned, was a “one-man whitewashing machine,”as Robert Proctor has put it, clearing some of the most horrific medical re-searchers, including Otmar von Verschuer (of sinister twin studies fame).5 De-scribing Hörlein’s values as “scientific, medical, and technical” overlooks hisresponsibility as a leader in a company using slave labor, producing medicinesand combat gases for the military, and one whose wartime drug testing prac-tices have not been fully explored. In short, Hörlein might have disliked theNazis, but he served them well.
Instead of following the trajectory of a drug, as Lesch and Bud have, other historians have chosen to follow the trajectory of a medical condition, track-ing the different therapeutic approaches that have been taken to deal with it.
This perspective has challenged another element of the standard narrative,namely that drugs cure preexisting diseases. Indeed, the availability of drugscan also lead to the creation of new diseases, whether by transforming acutediseases into chronic ones (diabetes), unmasking diseases of advanced age(Alzheimer’s), or raising incentives for defining a new disease category (hyper-activity). The two other books reviewed here (Watkins and Greene) have muchto say on the co-construction of drugs and diseases.6 For as infectious diseasesreceded among the most pressing medical problems in industrialized countries,the pharmaceutical industry turned toward a potentially much more profitablemarket, chronic diseases, of which patients would never be cured. A drug’s ef-ficacy, as Lesch has pointed out, does not result from a molecule’s propertiesalone. By adjusting not just the (magic) bullet, but by shifting the targeted dis-ease as well—what recent commentators have called “disease mongering”—one could produce a powerful hit between a drug and a disease. 5. Robert Koenig, “Reopening the Darkest Chapter in German Science,” Science 288 (2000): 6. Among other recent examples, see Robert A. Aronowitz, Unnatural History: Breast Cancer and American Society (Cambridge: Cambridge University Press, 2007); and Scott H. Podolsky,Pneumonia Before Antibiotics: Therapeutic Evolution and Evaluation in Twentieth-Century America(Baltimore, MD: Johns Hopkins University Press, 2006). B O O K R E V I E W S
In The Estrogen Elixir: A History of Hormone Replacement Therapy in Amer- ica, Elizabeth Watkins, whose previous book considered the social history ofthe contraceptive pill, explores the medicalization of menopause and the riseand fall (and rise and fall) of estrogen replacement therapy.7 Sexual hormonesentered therapeutic practice almost immediately after their discovery in the1890s when French physician Charles-Edouard Brown-Séquard injected him-self with extracts from guinea pig testicles. Then seventy-two years old, he re-ported feeling rejuvenated, prompting many other men to follow his lead. Inthe late 1930s, other hormones such as estrogens began to be marketed on alarge scale to women to treat some of the symptoms of menopause. However,the “estrogen empire” truly expanded when long-term hormone replacementtherapy became a standard practice for post-menopausal women. In the post-war years, advocates of “estrogen from puberty to grave” succeeded in raisinghigh expectations from hormone therapy, at a time when U.S. Food and DrugAdministration (FDA) approval did not require proof of efficacy, only safety.
Watkins explores how the pharmaceutical industry “sold” estrogen therapy tophysicians, who in turn “sold” it to their patients, leading to the consumptionof estrogen by 40% of post-menopausal women in the United States by theend of the twentieth century.
Unlike other recent authors writing on “disease mongering,” Watkins does not claim to reveal a hidden conspiracy of pharmaceutical manufacturers andphysicians.8 Industry and doctors played their part, but they were joined bywomen patients, the popular media, and government. Even more importantly,the medicalization of menopause was also the result of deep cultural forces inAmerican society, which increasingly equated beauty with youth, health withsexuality, and aging with an active life. Thus, when these forces definedmenopause as a problem, estrogens became the answer. The rise of long-termestrogen replacement therapy, Watkins argues, came about predominantly be-cause of the changing meaning of menopause in the twentieth century.
In 1975 an observed association between estrogen and endometrial cancer damaged the reputation of estrogen therapy, predictably leading to controver-sies about clinical trial methodologies. At the same time, feminist groups,trying to reclaim expertise about the female body, criticized the excessive 7. Elizabeth Siegel Watkins, On the Pill: A Social History of Oral Contraceptives, 1950–1970 (Bal- timore, MD: Johns Hopkins University, 1998).
8. See, for example, Christopher Lane, Shyness: How Normal Behavior Became a Sickness (New Haven, CT: Yale University Press, 2007).
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medicalization of menopause. In that tense political and scientific context, theFDA went so far as to mandate patient labeling for estrogens, instead of theusual physician labeling. By 1980, estrogen prescriptions had dropped by 50%.
Another source of criticism, not explored in the book, came from animal rightsgroups. These groups publicized the fact that Premarin, the best-selling estro-gen, was produced from the urine of pregnant mares, whose foals, once born,would likely end up in the slaughterhouse.
A fascinating aspect of Watkins’s story is how drugs can be rebranded in the face of falling sales. After years of decline, estrogen therapy rose to new heightswhen it was repackaged as a preventive drug against osteoporosis and heart dis-eases. In this radically new therapeutic perspective, the drug was not meant tocure, but to reduce risks. In 1992 Premarin became the most frequently prescribeddrug in the United States. But one decade later, when a multi-million-dollar, fed-erally funded clinical trial pointed to a number of increased health risks fromestrogen therapy and questioned its overall benefits, estrogen therapy again fellin disrepute.
The story that Watkins tells, using mainly published sources such as news- papers, magazines, and medical journals, shows how much the history of drugsbenefits from being placed in the context of the cultural history of particularconditions and diseases. The efficacy of a drug, far from being an intrinsic prop-erty, is a relationship between two flexible entities, a drug and a human con-dition. From Watkins’s history, it seems that cultural forces and randomizedclinical trials were the main determinants of estrogen therapy’s fate. One maywonder if, in her attempt to shy away from conspiracy theories, Watkins playsdown the importance of the pharmaceutical industry. Had she looked into (andbeen granted permission to access) the archives of Ayerst, one of the main pro-ducers of estrogens, and not just the advertisements they sponsored, she wouldperhaps have reached a slightly different conclusion. Indeed, the leveling of theinformation field between patients and physicians, which Watkins sees as char-acteristic of the late twentieth century and as resulting partly from the phar-maceutical industry’s willingness to disclose potential risks more openly, waspartially due to the industry’s fear of litigation, an issue which is conspicuouslyabsent from the book.
The physician and historian of medicine Jeremy A. Greene also explores “condition branding” in his Prescribing by Numbers: Drugs and the Definitionof Diseases. In a sophisticated and compelling account, Greene explains hownumerical values of physiological parameters became the basis for adjudicatingbetween the normal and the pathological in the second half of the twentieth B O O K R E V I E W S
century. Using extensive FDA and pharmaceutical industry archives, Greenefollows the history of three drugs: Diuril for hypertension, Orinase for dia-betes, and Mevacor for cholesterol. In so doing, he succeeds in making a muchbroader argument than can be found in studies based on a single drug or dis-ease. Greene shows how a quantifying culture in medicine produced a new kindof patient on a massive scale, namely, the patient who is symptomless but yetat risk. In a nutshell, the narrower the numerical interval for a normal physi-ological value (be it of blood pressure or blood sugar or cholesterol or so on),the larger the population that is defined as having a pathological condition orbeing at risk. As with the earlier concept of a healthy disease carrier, from Ty-phoid Mary to the genetic heterozygote, this new form of patienthood has broughtthe medicalization of previously healthy individuals to an unprecedented scale.
Unsurprisingly, this process has been closely linked to the availability of phar-maceutical drugs, and thus to the production of potential consumers.
Greene provides a fascinating account of pharmaceutical marketing and the complex relationships between physicians and pharmaceutical companies. How-ever, like Watkins, he does not describe the medicalization of risk and chronicdiseases as resulting exclusively from the aggressive marketing strategies of BigPharma, even though the latter, together with other market forces, did play amajor role. By taking into account the role of patient organizations, insurancecompanies, malpractice litigation, and other factors, Greene offers a much richernarrative of the redefinition of the normal and the pathological in the late twen-tieth century. Most importantly, the rise of chronic disease has resulted fromthe production of specific forms of biomedical knowledge in partnerships amongindustry, academia, and government. This does not necessarily involve “badscience” or the selling-out of academic science to corporate interests, but, moresubtly, the reframing of the research agenda around questions that serve, at thesame time, commercial, scientific, and public health interests. It would be hard not to notice that the new historiography of drugs has be- come an exceptionally vibrant and innovative field, as the four examples re-viewed here clearly attest. And the field can naturally be extended to include athird approach, not represented among the books under review, focusing on aparticular pharmaceutical company.9 This fecundity has given rise to a very 9. Most such volumes have either been commissioned by companies or written by independent scholars hampered by limited archival access. The genre has thus usually not yet proven as suc-cessful as studies of drugs or diseases. For a recent example to the contrary see Roy Church andE. M. Tansey, Burroughs Wellcome & Co.: Knowledge, Trust, Profit, and the Transformation of theBritish Pharmaceutical Industry, 1880–1940 (Lancaster, Eng: Crucible Books, 2007).
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welcome side effect, namely, a cure to some of the divisions among the historyof science, medicine, and technology. One can only conjecture as to some ofthe directions in which a reunified field might evolve. So far, the social and cul-tural history of drugs has remained surprisingly disconnected from the litera-ture produced by economic and business historians. From the macro perspec-tive in Alfred D. Chandler’s Shaping the Industrial Century to the more microstory in Louis Galambos and Jane Eliot Sewell’s Networks of Innovation,10 thereseems to be some room to inscribe particular modes of knowledge productionwithin the historical development of new visions of industrial production andthe market forces that structure them. Drug research can then be understoodas resulting from different “ways of knowing” connected to different “ways ofproducing,” as John Pickstone has suggested more generally for the history ofscience, technology, and medicine.11 Along this line, one wonders if the history of drugs would not benefit from being brought under a larger heading than those of individual drugs or patholo-gies, or, for that matter, companies. For example, even though the sulfa drugsand penicillin were both used as antibacterial agents, the sulfas probably hadmore in common with vitamins, and penicillin with vaccines, than they didwith each other. The actors’ categories of “biologicals” (or “biologics”) and“chemicals” brought together different drugs that presented similar produc-tion challenges, disciplinary commitments, regulatory frameworks, appropri-ation possibilities, and cultural currencies. A perspective that considered suchcategories would help us to draw a larger map of the therapeutic revolution inwhich drugs have figured so prominently.
10. Alfred D. Chandler, Jr., Shaping the Industrial Century: The Remarkable Story of the Evo- lution of the Modern Chemical and Pharmaceutical Industries (Cambridge, MA: Harvard Univer-sity Press, 2005); Louis Galambos and Jane Eliot Sewell, Networks of Innovation: Vaccine Devel-opment at Merck, Sharp & Dohme, and Mulford, 1895-1995 (Cambridge: Cambridge UniversityPress, 1995).
11. John V. Pickstone, “Working Knowledges before and after Circa 1800: Practices and Dis- ciplines in the History of Science, Technology and Medicine” Isis 98 (2007): 489–516.

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