Taking Pharmaceutical Innovation to the Masses - ACS Medicinal

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Taking Pharmaceutical Innovation to the Masses Philip C. Burcham* Division of Pharmacology, School of Biomedical Science, The University of Western Australia, Nedlands, 6007 Western Australia, Australia ABSTRACT: General levels of “pharmaceuticals literacy” are not high in contemporary societies. To address this educational need, in 2012 the University of Western Australia introduced an innovative multidisciplinary course for undergraduates within any degree program entitled PHAR1101: Drugs that Changed the World. Now ranking among the largest courses at the institution, PHAR1101 enrollments will likely approach 1000 students in 2017.

KEYWORDS: Pharmaceutical innovation, teaching, eLearning, scientific literacy “Two things are absolutely clear. First, science and its synergistic partner technology are really important in our daily lives. Second, the general population, both in the United States and abroad, suffers from a high degree of scientific illiteracy. As a general rule, we are ignorant of what is really important to us.” he opening lines of Dr. Eugene Cordes’ excellent Hallelujah Moments: Tales of Drug Discovery1 doubtless convey the frustrations of a pharmaceutical industry leader at the pervasive diversion of discretionary healthcare expenditure toward “alternative remedies” of dubious efficacy in our times. The likelihood that many of our fellow citizens possess a limited appreciation of the scientific principles underlying drug action, or of the strategies used to invent and test the efficacy and safety of new medicines, poses a distinct challenge to pharmacology, the discipline that stewards the scientific and clinical knowledge needed to use pharmaceuticals wisely. In a typical university, the teaching of pharmacology is confined to the curriculum studied by biomedical science, medical and pharmacy students, as well as those in allied health fields such as nursing, dentistry, and podiatry. Despite broad interest in new therapies and health-related issues within the general populace and across the student body, most universities provide few opportunities for students in the humanities and nonmedical sciences to explore the fascinating scientific, ethical, historical, and human dimensions of the modern pharmaceutical innovation enterprise. My colleagues and I seized an opportunity to address this situation when our institution announced a substantial overhaul of its curriculum in 2010. In addition to sharply reducing the number of undergraduate degrees, the university called for the development of accessible “Broadening Units” that expand student knowledge of fields beyond the disciplinary boundaries of their primary or secondary majors. To develop a course that

provides a basic introduction to pharmacology and pharmaceutical innovation, a collaborative group involving experimental and clinical pharmacologists, a toxicologist, clinicians, and historians assembled to construct a first year course entitled PHAR1101: Drugs that Changed the World. Opening for enrolments in 2012, PHAR1101 proved popular from the outset: from a founding class of 260 students, enrolments grew steadily so that the course will likely approach 1000 students in the sixth year of its availability (Spring semester 2017). In keeping with the strong demand, end of year student evaluations consistently reveal above average satisfaction with the course. In gratifying concurrence with its objectives, PHAR1101 has attracted enrollments from across the student body, including significant numbers of B. Science students as well as many B. Arts, B. Design, and B. Commerce candidates. The latter students often express appreciation for how PHAR1101 helps to “demystify” the scientific and medical complexities accompanying the use of pharmaceuticals in our world. Similarly, B. Science students frequently report that PHAR1101 kindled their interest in the pharmaceutical sciences and steered them toward graduate programs in pharmacy, medicinal chemistry, or pharmacology. PHAR1101 also appeals to “study abroad” students seeking a broadening experience during a semester or two in Perth; the 2016 class, for example, included exchange students from the United States, Great Britain, France, Holland, Malaysia, Italy, and Brazil. Since our experiences with this popular course may be of interest to faculty elsewhere who are seeking strategies to engage today’s students with the pharmaceutical sciences, I will

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DOI: 10.1021/acsmedchemlett.7b00173 ACS Med. Chem. Lett. XXXX, XXX, XXX−XXX

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“low mass” molecules, with the TNF-inhibitor infliximab used as an illustrative therapeutic agent. Readers seeking a more detailed yet publicly accessible overview of the PHAR1101 curriculum might consult the online unit information management system at UWA (https:// uims.research.uwa.edu.au/Units/PHAR1101/SEM-2/2016) or the UWA Handbook (http://handbooks.uwa.edu.au/units/ unitdetails?code=PHAR1101). In addition to highlighting scientific topics possessing intrinsic appeal, the popularity of PHAR1101 is a tribute to the enthusiastic involvement of many dedicated individuals with an aptitude and talent for teaching large class sizes.

highlight several features that I believe underpin the success of PHAR1101.

1. INNOVATIVE COURSE AIMS In keeping with our intention to accommodate students from a diversity of undergraduate programs, the PHAR1101 syllabus was designed to pursue several educational aims that transcend the science-focused objectives of a conventional pharmacology course: First, PHAR1101 seeks to convey an appreciation for how effective medicines promote human well-being by assisting the treatment and prevention of disease. Second, the course explores how the historical identification of new medicines helped foster the growth of an evolving science- and evidence-based approach to drug discovery and development. Third, PHAR1101 seeks to introduce students to the deep social impact medicines and other drugs have had upon human societies. Fourth, PHAR1101 endeavors to show how the development of effective medicines often builds upon new insights into the cellular and molecular mechanisms underlying human disease as well as advances in medicinal chemistry made by chemists. Finally, the course develops an appreciation of the ongoing medical and economic challenges to global health due to such factors as the escalating cost of drug development, antibiotic resistance, healthcare accessibility, and mental health policies.

3. HISTORICALLY-GROUNDED CONTENT While physicists frequently take a chronological approach to teaching their discipline, in pharmacology we are often guilty of ignoring the important historical context to pharmaceutical innovation, risking the unfortunate impression that new medicines mysteriously drop onto pharmacy shelves as if by magic. An effort was made to overcome this tendency when designing the PHAR1101 syllabus, assisted in part by helpful literature on the history of pharmaceutical innovation.2,3 Jie Jack Li’s Laughing Gas, Viagra and Lipitor4 and his more recent Blockbuster Drugs5 take an engaging, historically attuned approach to surveying progress in the pharmaceutical sciences; both volumes currently serve as primary “recommended reading” resources in PHAR1101. Such generalist books are supplemented by reading materials ranging from specialist reviews in academic journals6−9 to “popular science” books that narrate the historical development of ground-breaking therapeutic agents.10−12 Judging by student feedback, the use of a historically attuned approach in PHAR1101 helps make the scientific content less daunting to students from outside the medical sciences. Conversely, since the historical lectures can be challenging to B. Science students, PHAR1101 fulfils the expectation for “broadening units” at our institution, namely, that they expose students to disciplinary content that lies beyond their personal academic “comfort zones.”

2. CATCHY LECTURE MODULES The PHAR1101 course involves delivery of two lectures per week over a 13 week semester. While a typical pharmacology syllabus often gives in-depth attention to major therapeutic classes (e.g., cardiovascular drugs, anxiolytics, analgesics, etc.), the PHAR1101 curriculum structures lecture content into ten introductory thematic modules which comprise either two or four lectures. Briefly, the initial “Introducing Drugs” module involves a preliminary overview by a medical historian entitled “Health and Medicines before the Age of Science” as well as a lecture providing a basic appreciation of core pharmacodynamic concepts entitled “How Drugs Work.” The second module “Alcohol−the Oldest Drug,” includes a lecture on the historical and ethnographic aspects of alcohol use in different cultural settings, plus introductory lectures on “Alcohol and the Brain,” “Alcohol and Individual Harm” (explores Fetal Alcohol Syndrome and Alcoholic Liver Disease), and a thematic lecture by a “Russianist historian” entitled “Alcohol and Russia.” Subsequent modules include “Thalidomide−the Horror Drug,” “Chlorpromazine−the Liberating Drug,” “Penicillin−the Miracle Drug,” “Ether−the Kindest Drug,” “Mustard Gas−the Poisonous Drug,” “Nitroglycerin−the Explosive Drug,” and “Oral Contraceptives−the Revolutionary Drugs.” Each module usually involves lectures delivered by experimental or clinical pharmacologists, with historians and a lawyer providing extra insight into relevant topics. Typically, a significant medicine exhibiting an engaging historical narrative is presented as a prelude to reviewing subsequent advances that built upon the success or medical impact of the innovator molecule. The final module, “The Future of Drugs,” includes a lecture on the promise and pitfalls of personalized medicine as well as a lecture that explores the issues surrounding decisions to focus discovery efforts on “high mass” therapeutic proteins versus

4. FAIR ASSESSMENT The expectation that PHAR1101 would attract students from diverse cohorts required the careful design of appropriate assessment activities. The assessment centerpiece is a demanding end of year 2 h exam paper, which contributes 50% to the final grade, and comprises a combination of multichoice questions, short answer questions, and an essay. The exam is structured to assess a mix of course content drawn from the pharmacological sciences as well as historical and social science material. Additional assessment items include four summative assessments comprising online multichoice question-based tests, which are conducted under supervision at 3 week intervals in a large eLearning Suite (the four tests together contribute 20% to the final grade). Frequent bite-sized testing of this kind is a popular feature of PHAR1101 as it provides students with ongoing feedback on their progress throughout the course. Another assessment item is the Drug Discovery Pioneer Report (10% of final grade), a written exercise requiring investigation of the contributions of a key figure from pharmaceutical innovation history together with an exploration of subsequent scientific or clinical advances and their impact on the healthcare sector (Table 1). This exercise cultivates an B

DOI: 10.1021/acsmedchemlett.7b00173 ACS Med. Chem. Lett. XXXX, XXX, XXX−XXX

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Table 1. Key PHAR1101 Assessment Item Involves Students Conducting Research on the Life and Achievements of a Notable Pharmaceutical Innovator from Biomedical Research History; The Most Popular Drug Discovery Pioneers Chosen for Investigation by the 2016 Class Are As Shown: drug discovery pioneer James Black Daniel Bovet John Cade Jean Delay Paul Ehrlich Gertrude Elion Howard Florey Susan Band Horwitz Miguel Ondetti Elizabeth Lee Hazen Karl Link Leo Sternbach Youyou Tu Selman Waksman

innovator molecule(s) or pharmacological breakthrough

Table 2. In Addition to Conventional Lectures, PHAR1101 Course Content Is Supplemented by Online Delivery of Eight eLearning Modules (“eTutorials”) That Extend Knowledge of Drug Discovery and Testing Strategies Used during the Search for New Pharmaceuticals eTutorial

theme of eLearning module

1

bioprospecting and the search for drugs from nature disease model-testing in lab animals “Me-Too” drug discovery by rival commercial investigators

relevant health conditions

propranolol, cimetidine mepyramine, succinylcholine lithium chlorpromazine salvarsan, neosalvarsan

bipolar disorder schizophrenia syphilis

mercaptopurine, azathiopurine, allopurinol, acyclovir, etc. clinical testing of penicillin

childhood leukemia, organ transplantation, gout, herpes infections bacterial infections

2

angina, gastro-esophageal reflux allergies, general anesthesia

3 4 5 6 7

antimitotic action of taxanes cancer of the breast, ovaries, lungs, etc. captopril hypertension nystatin

fungal infections

warfarin chlordiazepoxide, diazepam, flurazepam, nitrazepam, etc. artemisinin, dihydroartemisinin actinomycin D, streptomycin

blood clots, stroke, etc. anxiety, convulsions, insomnia, etc.

8

astute clinical observation of unexpected drug effects rational drug design irrational discovery: high throughput screening of large compound libraries preclinical drug development: pharmacokinetics, metabolism and toxicity human drug testing: Phases 1, 2, 3, and 4

representative medicines or therapeutic areas highlighted colchicine, warfarin, artemisinin, others salvarsan, prontosil, others diphenhydramine, fexofenadine, saquinavir, atazanavir, others the “Sons of Sulfanilamide,” minoxidil, others zanamivir sorafenib, miraviroc ketotifen alzheimer disease therapeutics

eTutorial provides a basic awareness of the clinical testing protocols used to evaluate drug candidates while also surveying the main regulatory agencies that approve new medicines in the USA, Europe, Australia, and Asia (Table 2). Another well-received eLearning strategy adopted during “Lecture Review Sessions” held prior to the four summative tests involves students using their own mobile devices to compete in online quizzes against classmates.

malaria tumors (e.g., Wilm’s, Ewing’s sarcoma, etc.), tuberculosis

6. LOGISTICS AND STUDENT RETENTION While the popularity of PHAR1101 has posed significant challenges to our small pharmacology department, we have found that many issues can be mitigated using available technologies. For example, the introduction of campus-card screening technology helped to minimize the logistical challenges arising from the need to evaluate many hundreds of students within a strict time frame at our eLearning Suites on test days. Similarly, in an effort to counteract the student attrition and disengagement that can plague large undergraduate courses, extensive use is made of the capabilities of BlackBoard to maintain communication with PHAR1101 students throughout the semester of their enrolment. For example, BlackBoard allows prompt identification of students who fail to attend formal test sessions, allowing an e-mail to be sent to encourage them to participate in alternative test sittings. By permitting online self-enrolment of such students in “CatchUp” test sessions, such measures have ensured good levels of student retention relative to some large first year classes. On the whole, class feedback suggests that students appreciate technological and logistical innovations that ensure large courses run smoothly and efficiently. These outcomes were assisted by university investments, which modernized and expanded the e-Learning facilities available to pharmacology instructors in the School of Biomedical Science.

awareness that the pharmaceutical innovation enterprise has historically been a very human endeavor that involves risktaking individuals making pioneering discoveries and acting as resolute “champions” of their scientific insights. Students from nonscience backgrounds frequently excel during the Drug Discovery Pioneer exercise. The remaining 20% of the final grade involves completion of eight online quizzes that assess knowledge conveyed via eLearning modules delivered via the campus Learning Management System (LMS) (inf ra vide).

5. RICH ELEARNING CONTENT Soon after PHAR1101 was established, my interest was aroused by an article in Chemical & Engineering News, which highlighted a trend within US universities suggesting chemistry courses that incorporate eLearning tools and strategies are finding themselves rewarded by strong student enrolments. In response to such realities together with the need to accommodate rising enrollments within the tough fiscal environment prevailing on modern university campuses, I have employed instructional design authoring tools such as Articulate Storyline to prepare eLearning modules that are delivered at more or less weekly intervals during PHAR1101 via our campus LMS. The first six “PHAR1101 eTutorials” explore particular drug discovery strategies that facilitated the introduction of significant new pharmaceuticals, while the seventh eTutorial surveys the methods used to confirm that lead molecules identified in discovery programs possess acceptable “drug-like” pharmacokinetic and toxicological properties (Table 2). The final



CONCLUSION While attentiveness is needed to keep atop of demands and issues created by large, diverse classes, the success of PHAR1101 suggests that campus-wide student interest in C

DOI: 10.1021/acsmedchemlett.7b00173 ACS Med. Chem. Lett. XXXX, XXX, XXX−XXX

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(11) Lax, E. The Mold in Doctor Florey’s Coat: the Story of the Penicillin Miracle; Henry Holt: New York, 2005. (12) Hager, T. The Demon Under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug; Three Rivers Press: New York, 2006. (13) Drews, J. Drug Discovery: A Historical Perspective. Science 2000, 287, 1960−1964.

modern pharmaceutical innovation is potentially high. It is hoped that this brief survey of our course will inspire readers to explore novel curricular innovations that are applicable to their own campus settings with a view to promoting awareness of the achievements of the pharmaceutical innovation enterprise to which humanity owes so much.13



AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Philip C. Burcham: 0000-0001-8738-9335 Notes

The author declares no competing financial interest.



ACKNOWLEDGMENTS Many individuals have contributed to the success of PHAR1101: Peter Henry, former Head of UWA Pharmacology, conceived the bold idea of a pharmacology-themed “Broadening Unit,” while a senior clinical colleague, David Joyce, coined the appealing course name. Fiona Pixley, a clinically trained scientist, helped focus the syllabus on medically significant pharmaceutical innovations. Philippa Martyr, a historian with a rare capacity to cover large swathes of medical history, has progressively shouldered much of the historical teaching. Mathew Martin-Iverson, Mark Edele, Andrea Gaynor, Stephan Schug, Andrew Harman, and Thomas Ledowski have willingly contributed expertise as lecturers. Lucia Ravi has developed online resources to help students conduct librarybased research, while Shane McGurk (NextLearning, Perth, WA) is helping to create new eLearning resources for PHAR1101. Mary Anne O’Hara and Succorin Fernandes provided sterling administrative support from the outset. Lydia Burcham, Ke Nguyen, Richard Claudius, and Suraj Harinath helped with “crowd control” measures to ensure test days run smoothly.



REFERENCES

(1) Cordes, E. Hallelujah Moments: Tales of Drug Discovery; Oxford University Press: New York, 2014. (2) Bowden, M. E.; Crow, A. B.; Sullivan, T. Pharmaceutical Achievers: The Human Face of Pharmaceutical Research; Chemical Heritage Press: Philadelphia, 2003. (3) Sneader, W. Drug Discovery: A History; John Wiley and Sons: Chichester, 2005. (4) Li, J. J. Laughing Gas, Viagra and Lipitor: the Human Stories behind the Drugs We Use; Oxford University Press: New York, 2006. (5) Li, J. J. Blockbuster Drugs − The Rise and Decline of the Pharmaceutical Industry; Oxford University Press: New York, 2014. (6) Gaw, A. ’The Principles of a Future Pharmacology’: Johann Christian Reil (1759−1813) and His Role in the Development of Clinical Pharmacology. Eur. J. Clin. Pharmacol. 2016, 72, 13−17. (7) Rang, H. P. The Receptor Concept: Pharmacology’s Big Idea. Br. J. Pharmacol. 2006, 147, S9−S16. (8) Rubin, R. P. A Brief History of Great Discoveries in Pharmacology: in Celebration of the Centennial Anniversary of the Founding of the American Society of Pharmacology and Experimental Therapeutics. Pharmacol. Rev. 2007, 59, 289−359. (9) Cragg, G. M.; Newman, D. J. Natural Products: A Continuing Source of Novel Drug Leads. Biochim. Biophys. Acta, Gen. Subj. 2013, 1830, 3670−3695. (10) Jeffreys, D. Aspirin, the Remarkable Story of a Wonder Drug; Bloomsbury Publishing: London, 2004. D

DOI: 10.1021/acsmedchemlett.7b00173 ACS Med. Chem. Lett. XXXX, XXX, XXX−XXX