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Vol. 24, No. 20 April 9, 1999

Richard Axel, a Pioneer in Perception Studies, Is Named University Professor

BY BOB NELSON

Richard Axel, a pioneer in bringing the insights of molecular biology to bear on the study of perception, has been named University Professor, the highest academic rank at Columbia.

The action was approved by the Board of Trustees last month and announced by President George Rupp. In making the appointment, the Trustees increased the number of University Professors from eight to nine. The appointment allows Axel to teach in any department of the University.

Axel, a 1967 Columbia College alumnus, joined the faculty in 1974 and has most recently served as Higgins Professor of Biochemistry and Molecular Biophysics and professor of pathology. He continues his affiliation with the Howard Hughes Medical Institute, where he has been an investigator since 1984.

"I am pleased and honored to be appointed University Professor," Axel said. "I owe an enormous debt to this University. Thirty-five years ago, Columbia provided a scholarship allowing me to attend the College. As an undergraduate, I stood in awe of the University Professors, and it is therefore particularly meaningful to me to have been afforded this honor. When I returned as a professor in 1974, Columbia provided an environment allowing my laboratory to flourish.

"What is the significance of this appointment to a molecular geneticist working on perception? The study of perception has a distinguished history that has often ignored biology. With the demystification of the brain, molecular biology can now approach the previously tenuous relationship between genes and behavior, cognition, memory and perception.

"Thus, what we do has emerged into a multidisciplinary endeavor. The University Professorship will hopefully afford an opportunity for interactions that bring molecular biology closer to the disciplines of psychology and, at the extreme, perhaps even philosophy."

Rupp said, "Richard Axel richly deserves appointment as University Professor. His deeply disciplined investigations are driven by a wide-ranging intellectual curiosity nourished in the humanities and social sciences as well as the sciences. Columbia is proud to confer this entirely apt honor."

Provost and Dean of Faculties Jonathan R. Cole said, "Richard Axel is one of the world's leading biologists. His fundamental discoveries in biochemistry, genetics and molecular neurobiology have been recognized by his peers in the scientific community-from his election to the National Academy of Sciences at a tender age, to his more recent recognition for closing the genes that encode odorant receptor proteins.

"What is perhaps less well known is the extraordinary reach of Richard's knowledge and the breadth of his interests that inform the insights in his work and lectures. We like to think that this was developed through his encounters with the liberal arts and Core Curriculum during his days at Columbia College."

Most recently, Axel and his colleagues have applied the power of genetics to an understanding of olfactory sensory perception.

"Perception is a gateway to understanding the mind," Axel said. By understanding how sensory information is obtained, transmitted to the brain and then processed into meaningful information, he said, scientists can learn a great deal about how the brain works. The sense of smell provided a particularly fascinating enigma because of its ability to distinguish tens of thousands of different molecular structures as distinctive odors. "We therefore first asked, how does the brain recognize the vast array of odors?" Axel said. "The logical next step is the question of perceptual discrimination. How does the brain know what the nose is smelling?"

In 1991, Axel and a postdoctoral research fellow, Linda Buck, now a professor at the Harvard Medical School, provided a solution to the first question when they cloned the genes encoding odorant receptor proteins, the molecules that first interact with odors in the nose. They showed that in mammals, there are about a thousand different receptors and, therefore, a thousand different genes encoding the receptor proteins. Because the mammalian genome consists of from 50,000 to 100,000 genes, approximately one to two percent of the genome is dedicated to the production of receptors that recognize odors.

"The enormous amount of genetic information devoted to smell perhaps reflects the significance of this sensory system for the survival and reproduction of most mammalian species," Axel noted.

In Axel's other work, with the advent of recombinant DNA technology, he recognized that isolating and analyzing genes would not necessarily disclose what a gene does or how it controls an activity. In 1976, Axel reasoned that it would be necessary to introduce cloned genes into foreign cells and determine how their expression was controlled-how the body decides when to turn a gene on and when to turn it off.

To this end, Axel, working with a student, Michael Wigler, now investigator at Cold Spring Harbor Laboratory and adjunct professor at Columbia, developed procedures that permitted the stable introduction of any gene into cultured cells, such that these genes function normally in their new cellular environment. This process is now used by pharmaceutical companies to make complex human hormones and growth factors, such as erythropoietin, which stimulates the production of blood cells, an essential component in the treatment of end-stage kidney disease. Licenses on the process account for a large component of Columbia's annual technology licensing income, which in fiscal 1998 was $86 million.

In the early 1980s, Axel exploited this technology to isolate the key genes that produce the CD4 and CD8 receptors on human immune cells, which are central to activation of the human immune system. He subsequently demonstrated that the CD4 receptor is the major site of binding for the AIDS virus, work that shed important light on how the virus infects healthy cells and ultimately provided new molecular targets for drugs to treat the disease.