Originally created 09/13/03

Professor looks at researcher's work



Millions of patients rely on drugs that are based on a discovery 50 years ago by a Medical College of Georgia researcher. Yet the late Raymond P. Ahlquist never got his due or the Nobel Prize that some had predicted, in part because of vicious political infighting in the scientific community.

The fate of Dr. Ahlquist provides a look at a bare-knuckles battle and rivalry over ideas that sometimes belie the antiseptic clinical world of medical research that the public imagines, a medical historian from England said.

Dr. Cay-Ruediger Pruell, from the University of Durham, is doing research in Augusta this week for a book about the history of receptor theory, of which Dr. Ahlquist and his work will play an important part.

The controversy centered on Dr. Ahlquist's work on receptors, chemical "keys" that lie on the cell surface and can bind with other substances, such as drugs, that cause the cell to do something. The idea was first broached in the late 1800s and much discussed in the early 20th century but wasn't revived as a concept until the 1930s, Dr. Pruell said. And then it was not widely accepted in pharmacology, where there was a rivalry among the transmitter theorists, who held that there were two classes of transmitters that acted directly on cells.

Dr. Ahlquist, however, theorized that there were two receptors on cells in the cardiovascular system, alpha and beta, and that beta reacted with adrenaline and similar substances to speed up the heart. His paper was initially rejected and was published in 1948 in the Journal of Physiology only with the help of fellow MCG researcher William Hamilton, said Lowell Greenbaum, the vice president emeritus for research at MCG.

Even after it was published, the "transmitter people" continued to criticize the idea and others who promoted it, Dr. Greenbaum said.

"And they were vicious, vicious people," he said.

"You get everything in science that you get in politics or in the church," Dr. Pruell said.

Dr. Ahlquist himself was somewhat modest about promoting the theory, saying he developed it only to give his students a better concept to work with. Yet it sparked J.W. Black in England to begin to develop a drug that could block that beta receptor, a drug that he later tested in Dr. Ahlquist's lab. It would become propranolol, the first beta blocker.

This year, 107 million prescriptions were written for beta blockers, according to pharmaceutical analyst IMS Health, to treat severe high blood pressure and heart problems such as cardiac arrhythmias. By the 1970s, receptors had been embraced and Dr. Ahlquist's work opened the door to search for highly specific receptors and then drugs to take advantage of them, Dr. Pruell said.

For their part, Dr. Ahlquist and Dr. Black were awarded the Albert Lasker Award for Clinical Research in 1976. Many of the Lasker winners went on to claim the Nobel Prize, and at the time, Dr. Ahlquist said his chances were "pretty good" to get the Nobel, "even if one of the Nobel officials is a personal enemy of mine."

But he died in 1983 without it.

"His enemies black-balled him," Dr. Greenbaum said. "It was a miscarriage of scientific justice."

Dr. Black went on to win the Nobel Prize in physiology or medicine five years later.

"As you well know, I owe a great deal to his brilliant discoveries of fifty years ago," he wrote to Dr. Ahlquist's widow, Dorotha. "I've stood on the shoulders of a giant."

Reach Tom Corwin at (706) 823-3213 or tomc@augustachronicle.com.