FROM THE ACS MEETING
Many undergraduates are likely to find themselves working in the pharmaceutical industry after they graduate, but they usually aren't introduced to medicinal chemistry or drug discovery as part of their education. That situation is starting to change.
A group of professors shared their experiences teaching medicinal chemistry to undergraduates in a symposium at the American Chemical Society national meeting last month in New Orleans. The symposium was sponsored by the Division of Computers in Chemistry. Symposium organizer J. Phillip Bowen, professor of chemistry and director of the Center for Biomolecular Structure & Dynamics at the University of Georgia, intends for this to be the first in a series of symposia on teaching medicinal chemistry.
In his introductory remarks, Bowen explained why he believes chemistry departments should teach medicinal chemistry. First, the topic is "intellectually stimulating and challenging," he said. Plus, students who don't intend to go into research careers are often preprofessional students who want to go into medicine, so the topic is directly applicable to their prospective careers.
Bowen believes that a medicinal chemistry course should include both pharmacology and organic synthesis. However, "the drugs must be chosen judiciously because sophomore organic chemistry students know a finite set of reactions," he said. He also advocates including computer-assisted drug design methods in the course. Students at Georgia have had hands-on laboratory sessions using Tripos software.
Many professors who might be called upon to teach such courses--particularly at smaller schools--don't have a background in medicinal chemistry, Bowen pointed out. They can gain expertise in a variety of ways--by reading the medicinal chemistry primary literature or by attending workshops or continuing education courses on the topic. For example, ACS offers short courses on medicinal chemistry and computational chemistry and computer-assisted drug design.
Bowen believes that chemistry departments are an appropriate venue for medicinal chemistry courses, even at universities with a school of pharmacy. "Most schools of pharmacy couldn't handle the extra students," he said. Plus, the primary mission of pharmacy schools is training pharmacists, making many of the topics in the pharmacy school inappropriate for chemistry students. "Pharmacy and chemistry students have different needs," Bowen said, "but there are overlaps such as understanding structure and drug classes."
"The dean called to ask me if I would be interested in teaching one," Richard B. Silverman, professor of chemistry at Northwestern, told the audience. Silverman agreed, if he could have a quarter off to prepare the class. The preparation turned out to be harder than he anticipated. When he looked for a textbook, he found that there weren't any. So he decided to write one himself, which was published in 1992, called "The Organic Chemistry of Drug Design and Drug Action." A new edition is planned for late 2003 or early 2004.
Silverman had ulterior motives in wanting to teach a medicinal chemistry course. The course offered an opportunity to "refresh the memories of undergraduates about organic chemistry," he said. The class was designed as a survey course that looked at how organic chemistry is involved in the design, development, and action of drugs. In addition, by requiring students to write a term paper, he could give them their first exposure to literature searches and chemistry drawing programs.
Silverman considers the term paper to be valuable for determining the students' grasp of the course material. The students select any drug from the "Physician's Desk Reference," with the restriction that the drug can't be a natural product, endogenous compound, or peptide or protein. The students address a list of questions about their chosen drug. They write the papers in the style of ACS's journal Accounts of Chemical Research, and structures included must be drawn on the computer.
At the University of Georgia, medicinal chemistry was first offered in 1999 as an organic chemistry special topics course. It was well received by the students, Bowen said, and was offered again in 2001. Now, the course has been approved as a permanent offering.
Most of the undergraduate chemistry majors at Georgia don't plan to become chemists, Bowen said. Instead, many of them are premedical, prepharmacy, or predentistry students. "They still have to be taught traditional chemistry," he said, "but we want special topics courses that are tailored to the interests of the students."
ANOTHER REASON for teaching medicinal chemistry is that few students understand how drugs are discovered and developed, Bowen said. "They read about issues in the paper but don't understand them," he said. "Part of my role is to educate students on how drugs are discovered, regulated, and make it through clinical trials."
When Terry P. Lybrand moved to Vanderbilt University, he was given the assignment of resurrecting a class in medicinal chemistry. Previously, the medicinal chemistry course had been a "basic" chemistry course for health science majors, said Lybrand, who is a professor in the chemistry and pharmacology departments. Later, it morphed into an upper division elective in the organic chemistry sequence. After the instructor retired, Vanderbilt no longer offered the course because other faculty weren't comfortable teaching it.
Lybrand decided to remake the medicinal chemistry class into a hybrid of two classes he had taught at the University of Washington, Seattle--molecular biophysics and "traditional" medicinal chemistry. He doesn't talk about synthetic pathways because other electives address that topic.
"The big difference in the course now is that I teach about drug classes in the context of drug-receptor interactions to the extent possible, and introduce modern techniques for drug discovery and development where appropriate," Lybrand told C&EN. "I have also chosen to include a good deal more pharmacology than would normally be covered in an undergraduate class."
In his lectures, Lybrand emphasizes current developments and therapies. "Students often feel that we're giving them yesterday's story," Lybrand said. "If we can give them fresh-off-the-presses information, it makes them think it's more relevant."
A large portion of the students in the class--80 to 90%--are junior and senior undergraduates majoring in chemistry, molecular biology, and neuroscience. Their postgraduation plans include graduate school, medical school, law school, and business school. The rest of the students are first-year graduate students in chemistry, pharmacology, or the joint M.D./Ph.D. program. Most of the students have previously taken organic chemistry, basic biology, biochemistry, and physical chemistry.
The first time the course was offered, "several students dropped out because they wanted an advanced bioorganic synthetic methods course," Lybrand said. But that wasn't a typical reaction. "Almost all students have responded enthusiastically," he said. In fact, course scheduling and classroom capacity are becoming more difficult because of rapidly growing enrollment. Lybrand has even managed to "corrupt" a few preprofessional students into becoming Ph.D. students.
Chemistry Departments at smaller colleges and universities are also offering medicinal chemistry classes.
J. Philip Bays, a chemistry professor at St. Mary's College, Notre Dame, Ind., wanted to teach medicinal chemistry to provide a review of chemistry including topics in organic chemistry, biochemistry, and physical chemistry. He also wanted to teach his students what is involved in finding a new drug.
Bays thought that it would be fun to structure his medicinal chemistry class as if it were a company. He would be the company's president, and the students would be the employees.
His course outline was dubbed the "president's view" of what they needed to accomplish. He felt they needed to understand how drugs work, how targets and lead compounds are identified, and then how they are optimized. He also wanted to teach them the issues surrounding patents and clinical trials.
THE REALITY turned out different than the conception. At first, Bays provided the background information that the students needed. However, he was teaching two courses for the first time that term, which naturally increased the required preparation times. In February, he sent out a "reorganization memo." The course (company) was reorganized so that the students (the employees) shared the work of teaching by giving classroom presentations, an approach that worked very well.
Each of the students in Bays's class selected a drug for a project. The purpose of the project was to apply what they learned in the class to a specific example and then explain it to the class. Bays was also interested in whether the students could use the primary research and patent literature to find the necessary information. Because St. Mary's is a small school, access to the literature was an issue. Bays found that the students waited until late in the semester to begin and then used the Internet rather than the original literature, making the project reports somewhat more superficial than he had planned.
Bays said that he would make changes the next time he offers such a course. He would increase the number of objective assignments to make evaluating the students more uniform. He would also address fewer topics in more depth. Finally, he would take a "more programmed approach" to the project by giving the students more guidance in what they should do.
E. Eugene Gooch, a chemistry professor at Elon University, Elon, N.C., described the medicinal chemistry courses taught by him at Elon and by Anne G. Glenn at nearby Guilford College in Greensboro, N.C. Elon first offered the class in 2002, whereas Guilford has offered the class intermittently since 1994.
Gooch noted that medicinal chemistry provides a potent context to introduce selected advanced topics in physical and physical organic chemistry. Because Elon and Guilford are smaller colleges, however, they don't have a physical chemistry prerequisite for medicinal chemistry classes, which would reduce enrollment too much, Gooch said.
Gooch and Glenn have made their medicinal chemistry courses attractive in other ways. Scheduling the courses in the evening has minimized conflicts with other classes. And Gooch and Glenn have made their classes topical by bringing in external speakers and presenting case studies in drug development and synthesis.
Davidson College, in Davidson, N.C., recently started a chemistry minor and needed new classes to attract the students minoring in chemistry, who are primarily premed students, as well as chemistry majors who are earning a non-ACS-certified degree. Because that pool of students had not studied physical chemistry, the classes had to emphasize topics from general and organic chemistry. The classes also had to be taught by existing faculty.
Erland P. Stevens, assistant professor of chemistry, described a medicinal chemistry course designed to meet those objectives. The course, which was established for juniors and seniors, focused on the chemistry rather than the biology. It was offered for the first time in fall 2001. As expected, the majority of the students were chemistry minors. The department hoped that ACS-certified majors would take the class as well but realized that they don't have enough flexibility in their schedules to fit in chemistry electives.
Stevens thought that he had some weaknesses the first time he taught the course. Because he was trained as a synthetic organic chemist rather than a medicinal chemist, some of the medicinal chemistry topics were a stretch for him. Many questions required additional research outside the class to answer. "That was at times frustrating for me as well as the students," he told C&EN.
He has been working to further educate himself in medicinal chemistry. For other professors who are unfamiliar with medicinal chemistry, he recommended a weeklong residential school on medicinal chemistry offered each summer at Drew University in Madison, N.J.
ONE SHORTCOMING of the classes discussed in the symposium is that few use computer labs to teach computer-assisted or structure-based drug design. Barriers to the introduction of these tools include cost and time constraints in the classroom.
But two of the speakers described examples of commercial software programs that could bring structure-based drug design exercises to the classroom. Other companies also offer software that can be used in the undergraduate classroom.
George D. Purvis III, vice president of CAChe Group, a division of Fujitsu America in Beaverton, Ore., described his experience in developing computational experiments for teaching structure-based drug design. Purvis believes that computers can help students better learn how drugs work. "Words are not enough," he said. "You can tie words and pictures together" with computers.
The focus at CAChe Group was to develop labs that could be run in about an hour. The scripted exercises include activities such as viewing and analyzing proteins and docking ligands into proteins.
The software has been used in a course on computational biochemistry methods at the University of Florida, according to Purvis. The students worked through the exercises independently. Some undergraduate students even went on to use the software in their own research projects and wrote theses on their work, Purvis said.
Peter Gund, formerly with Gund Consulting Services and now with IBM Life Sciences, described a program called Molecular Conceptor Courseware, which is available from the company Synergix in Jerusalem. The program provides background information in various disciplines "to fill gaps in the knowledge of practicing modelers," Gund said.
The material is divided into three major sections. The first section provides an overview of the pharmaceutical industry and of drug discovery and development, the second section covers the molecular basis of drug design, and the third section presents strategies in drug design.
Gund suggested that the courseware can be used as a tool for professionals to teach themselves about drug design. He also recommended it to professors and students for curriculum enrichment in organic and medicinal chemistry.
The symposium speakers are at the forefront of teaching medicinal chemistry to undergraduates, but they are by no means the only ones. The number of schools offering medicinal chemistry courses within chemistry departments is "exploding," Bowen said. "I believe that every chemistry department will be offering classes like this within 10 years."
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