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"Designing drugs" sounds trendy, but it accurately describes how some remarkably effective drugs are developed. In this case study we'll follow the steps of drug design, from initial research on the targeted disease, to the drug's use in humans. Gleevec (STI-571) is our example.

A study in monkeys offers the first evidence that a leading drug developed to fight Ebola works against the strain causing the current outbreak in West Africa. Six animals were infected with a very high dose of the virus and then, three days later, half were given the drug, TKM-Ebola-Makona, which was designed specifically to fight the West African strain. The monkeys that received the drug survived, but all three untreated monkeys died, researchers reported on Wednesday in the journal Nature.

This video excerpt from NOVA examines the promise and realities of developing drugs designed to treat genetic disorders. The video presents the story of one patient, Michael McCarrick, whose lungs were devastated from years of suffering from cystic fibrosis. After researchers identified the gene involved in cystic fibrosis, it took decades to find ways to fortify the faulty protein responsible for the serious illness. While two drugs, including one called Kalydeco, offer a small number of patients hope that they will not have to endure a lung transplant, it may be years and several hundred million more development dollars before effective drugs are available for a wider population.

Within a year, Stein's team had designed a clinical trial protocol that turned standard research practices around 180 degrees, launching what it now calls the Signature Clinical Trial Program. Instead of a patient traveling to one of several research sites, Novartis would send the investigational drugs to his or her local oncologist's office. Instead of testing hundreds or thousands of genetically unscreened patients, the company would accept only patients who had the genetic markers the drugs were supposed to target. Instead of waiting months, patients could access the treatments in two or three weeks. Instead of running a large-scale trial to investigate one or two questions, clinicians could conduct smaller, rapid proof-of-concept studies to quickly rule out the tumor types that don't respond to a study agent and identify other tumor types that are potentially treatable with the drug and worthy of further study.

Before the discovery of insulin in 1921, being diagnosed with Type 1 diabetes was a death sentence. Despite the successful management of diabetes with purified animal insulin, potentially severe side effects were abundant, and alternative ways to produce insulin were needed. This case study guides students through the history of using insulin to treat diabetes, focusing on the development of recombinant DNA technology and the world's first bioengineered drug, recombinant human insulin, which is now used worldwide to treat diabetes. Through the course of this case, students consider the central dogma of molecular biology, the development of recombinant DNA technology, drug design, the importance of recombinant proteins to our society, and the ethical analysis and debates that occur as a result of some scientific discoveries. This case was developed as an introduction to an upper-division biotechnology course focusing on recombinant protein design and production, but could also be used in molecular biology, biochemistry, or introductory biology courses to highlight recombinant DNA and biotechnology.

This clicker case was designed to teach students about basic enzyme structure, mechanisms of enzyme inhibition, and mechanisms of drug resistance. The story follows Oliver Casey, a patient afflicted with Chronic Myelogenous Leukemia (CML). CML is caused by a chromosomal mutation that affects the tyrosine kinase ABL, an enzyme important in regulating cell growth and proliferation. The chromosomal mutation gives rise to the BCR-ABL fusion gene that produces a constitutively active ABL kinase, which causes the leukemia. In May 2001, the Food and Drug Administration approved the use of a rationally designed tyrosine kinase inhibitor, imatinib (Gleevec®), for the treatment of CML. During that same month, Gleevec made the cover of TIME magazine, described as "new ammunition in the war on cancer." The case is structured for a flipped classroom environment in which students view preparatory videos (including one by the author) on their own before beginning the case. Written for a first-year introductory biology course, the case could also be adapted for AP/Honors high school biology or a cancer biology course.

In a creative stroke inspired by Hollywood wizardry, scientists from Harvard Medical School and Technion-Israel Institute of Technology have designed a simple way to observe how bacteria move as they become impervious to drugs. The experiments, described in the Sept. 9 issue of Science, are thought to provide the first large-scale glimpse of the maneuvers of bacteria as they encounter increasingly higher doses of antibiotics and adapt to survive - and thrive - in them.

This clicker case study follows a dialogue between two college students, Lucy and Dan, as they discover how alternative splicing of mRNA molecules can allow a single gene to code for multiple proteins. Dan is participating in a clinical trial for a drug that may treat his migraines by inhibiting calcitonin gene-related peptide, and Lucy is working in a summer research lab that studies the protein calcitonin. They soon realize that the two proteins are both encoded by the same gene, and through their questioning and dialogue they come to understand the phenomenon of alternative splicing. They also learn about other steps of mRNA processing and about monoclonal antibodies. This case was designed to be taught in a flipped classroom, but could easily be adapted for a more traditional classroom setting if content covered in the pre-class videos is covered during the case study instead. It was designed for an introductory-level molecular biology course, but could be adapted for higher levels by including more information about the physiology and regulatory mechanisms involved.

This PowerPoint-driven case study presents three different stories, each of which explores an aspect of membranes. The first (The Exploding Fish) covers diffusion, specifically addressing the question of why animal cells explode in freshwater but fish do not, and differences between saltwater and freshwater fish. The second case (The Pleasurable Poison) is designed to show that alcohol can slip across membranes and also highlights some of the problems of ingesting this toxin. The third case (The Dangerous Diet) explores a weight-loss drug, DNP, and how it operates in mitochondrial membranes. The first of these case studies also includes a number of "clicker" questions. These cases were originally designed for a semester-long, introductory biology course for non-majors, and instructors can choose to use one or all of the cases to suit their course.

When Jordan is diagnosed with brain cancer (glioblastoma multiform), his college plans are unexpectedly put on hold. This scenario is presented in order to teach students about gene regulation, as the efficacy of the drug Jordan receives for post-surgical treatment is dependent upon the activity level of a gene encoding a protein involved in DNA repair. This "flipped" case study requires students to prepare in advance outside of class by watching several short videos that have been selected to teach the basics of how cancer forms as well as the role of epigenetics in gene silencing. Inside of class, the case is delivered using progressive disclosure format in which students gradually receive additional information to answer a series of directed questions. To determine a treatment plan for Jordan, students analyze data from a research study involving patients treated for his specific type of cancer. The case is designed for advanced high school biology classes as well as lower-level undergraduate general biology courses for non-majors and majors.

This case study presents the story of "Nick," a student who has been assigned the task of writing a research paper describing the fundamentals of chemical bonds and how they relate to human life. When Nick experiences difficulty remembering information about the different types of chemical bonds, he turns to his tutor, Josh, for help. Josh explains orbitals and valence electrons to Nick, and then they together review nonpolar and polar covalent bonds, ionic bonds, and hydrogen bonds. A final practical application exercise requires that students write about how different types of chemical bonds may relate to the development of Alzheimer's disease and to the mechanism of action of potential drug treatments.  The case is presented with PowerPoint slides and is designed to be used with a personal response system ("clickers"), but students can instead record their answers on paper or share them verbally.  The content is appropriate for use in high school and undergraduate introductory chemistry and biology courses.

In this case study, students will have the opportunity to model the spread of tuberculosis and development of antibiotic resistance in a hypothetical prison environment. After reading a brief handout and viewing a short video, students play a simulation game by first identifying a group of prison inmates represented by index cards. The placement of the cards will influence how drug resistance spreads from one inmate to another. Using a dice roll to mimic random probability of infection and antibiotic misuse, students then track the development of resistance to four specific antibiotics, determined by selection of playing card suit. Opportunity for release or transfer on inmates from one facility to another introduces a further level of complexity, allowing students to study resistance spread. This activity was originally designed for a section of an upper-division biology course about antibiotic resistance, but it would also be appropriate for lower-division undergraduate and high school biology courses discussing antibiotic use.

In this case study, we'll follow the process of developing an edible vaccine for the hepatitis B virus and explore practical details of genetic engineering techniques.