Two Words: Classical Pharmacology

For the past few decades, biology advisors have been whispering one word in the ears of talented undergrads: genes. It's good advice--molecular biology and genetics have blossomed, creating new tools for research and identifying new targets for treatment of disease. But the new golden word of advice might be the same as an old one: classical pharmacology.

As the armies of molecular biologists and geneticists have marched on, they've left in their dust more potential drug development targets than anyone has been able to exploit. And that has led to a problem: Classically trained pharmacologists are suddenly scarce. And very valuable.

Old-school pharmacologists used to be the backbone of drug discovery. They tested the efficacy of a drugs in vitro, developed animal models to test molecules in living systems, and analyzed tissues for signs of drug-specific activity. Then they conducted more animal studies to peg the optimal dosage for human clinical trials.

But the field became passé. Pharmacology departments embraced the new field of molecular pharmacology, a hybrid of molecular biology and pharmacology. The field uses the tools of molecular biology to sort out how molecules interact with receptors and how those interactions in turn affect cells and systems.

"Classical pharmacology hasn't got the glitz and glamor that manipulating a gene has," says James Barrett, vice president of neuroscience discovery research at Wyeth-Ayerst, a division of American Home Products Corporation in Princeton, New Jersey.

Molecular pharmacology, drawing on the work of geneticists and molecular biologists, has turned up multitudes of interesting receptors and other drug targets, but now scientists in the pharmaceutical industry face a bottleneck. They have to move candidate drugs into the clinic, where they might eventually be approved for human use. Molecular pharmacology studies, such as gene array experiments, that show a small molecule inducing expression of useful genes can't predict what that molecule will do in the complex system of a mouse, much less a human being. That's a job for classically trained pharmacologists.

The combination of fewer classically trained pharmacologists and increased demand for taking target molecules from the lab to the clinic has pharmaceutical companies scrambling to find enough researchers to fill their needs, says Ewan MacIntyre, executive director of pharmacology at Merck Pharmaceuticals in Rahway, New Jersey.

For people with the right training, this situation spells opportunity. Even if you're on a molecular pharmacology track, classes in physiology can give you an advantage in the job market. Even better, consider a lab rotation that puts you in the lab of a classical pharmacologist for a period of time, or choose a postdoc appointment or internship that allows you to pick up pharmacology skills. The investment could pay off when it comes time for job interviews.

Once employed, classically trained pharmacologists may find more opportunities for advancement than other researchers. A pharmacologist's training encompasses the entire spectrum of the drug discovery process: identification and validation of targets, study of preclinical animal models, determination of dosing schedules, and testing of toxicity in clinical trials.

In the right organization, that broad knowledge may endear a young scientist to upper management and provide opportunities for quicker advancement. "Their unique perspective automatically makes [classically trained pharmacologists] more valuable in a drug development environment... they have a broader integrated knowledge of how drugs interact in living systems than molecular biologists. My belief is that that allows them to move into managerial positions more quickly," says Cynthia Kuhn, a professor of pharmacology at Duke University in Durham, North Carolina.

Rodney Lappe agrees. In 1980, Lappe earned a doctorate from Indiana University with an emphasis in classical pharmacology. After a postdoc at the University of Iowa, he joined Wyeth Pharmaceuticals, a division of American Home Products Corporation in Madison, New Jersey, as a cardiovascular pharmacologist. Initially, his work involved characterizing the effects of bioactive peptides on renal function, organ blood flow, and arterial pressure in animal models. Although he hadn't planned a managerial career, he quickly found himself moving up the ladder: He went on to lead several projects and coordinated external collaborations with biotech companies. After 7 years at Wyeth, he moved to Rhone Poulenc Rohrer in King of Prussia, Pennsylvania, for a brief time before being named head of cardiovascular research at Ciba Geigy in Summit, New Jersey.

Lappe believes that his training in classical pharmacology lent him an advantage. "My publication record and experience in [cardiovascular pharmacology], my understanding of the models, the [animal] systems in which I had worked as a pharmacologist--these were clear driving points in the decision to hire me," says Lappe, who left Ciba Geigy in 1997 to become executive director of cardiovascular and metabolic disease discovery at Searle Pharmaceuticals in St. Louis, Missouri. "In our leadership team at Ciba, it was acknowledged that I was the only true classical pharmacologist," he says. "The head of the department thought it essential to have at least one. Otherwise, it would have really diminished the ability to look at all aspects of the data that go into making senior level decisions. It was acknowledged several times [by the management team] that my training had served me well," says Lappe.

The classical pharmacologist is not a dying breed. And Lappe is looking for a new generation of pharmacologists. "Do I discount molecular pharmacology? No, we'd love to hire a bunch more [molecular pharmacists] as well. But also look at people who bring in a wider breadth of experience, because generally those are the people who adapt and flourish in industry."

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