Back When Byetta Began

Then Dr. Eng had to show that exendin had biological activity. “Otherwise, it’s just another peptide.”

In a series of journal articles starting in 1990 he proved that activity and that exendin acts on the glucagon-like peptide 1 (GLP-1) receptor. The Journal of Biological Chemistry published his initial findings. His first article on exendin from the Gila monster came out in the April 15, 1992, issue of The Journal of Biological Chemistry. This article is so important in the history of diabetes that a free full-text version of it is online.

So, what’s so important about exendin’s GLP-1 action? A scientist named Joel Habener at the Massachusetts General Hospital had found that GLP-1 has a unique and powerful activity. Many hormones stimulate insulin secretion, but GLP-1 stimulates insulin secretion only when our blood glucose level is high.

But GLP-1 itself breaks down in a matter of minutes, so the only way that we could use it would be by a continuous infusion drip. Not fun.

The form of exendin that Dr. Eng synthesized from the Gila monster, however, stays in our bloodstream for hours. It then became clear to Dr. Eng that it could be a valuable medication for people with diabetes.

So he tried to get the Veterans Administration, where he has spent his entire career, to patent his invention. But at that time the VA was only interested in patenting inventions that were specific to veterans, like spinal cord injury, loss of limbs, or prostheses.

“That put me in a difficult position,” he told me, “because it meant I had to essentially make a bet. Patenting it came out of my pocket with no guarantee that anything would come of it.”

He filed his patent application on exendin in 1993. Two years later the United States Patent and Trademark Office issued patent 5,424,286 to him.

Then, he went around to try to interest the drug companies. At Lilly he met with people in chemistry, manufacturing, and physiology all day long for a half-hour each. “It was like a job interview.”

They turned him down. But the biotech firms like Amylin Pharmaceuticals are willing to take more risks than big companies like Lilly. And in October 1996 Dr. Eng negotiated a license with Amylin, which was finally able to offer Byetta to people with diabetes last year.

All along the way the Byetta story has been full of ironies. One of the first was the fact that while Lilly turned down the chance to develop Byetta alone, it was the company that Amylin turned to in order to jointly market it.

Another is that Dr. Eng had never seen a Gila monster when he invented Byetta. It was only a year or two ago that he finally got to see one, he told me when we talked again this week. He was in a film about Gila monsters made by a wildlife expert in England that U.S. public television showed.

One of the strangest ironies is that none of Dr. Eng’s research articles or his patent on extendin even mention the weight loss that it often leads to. I asked him this week when he first realized that it could lead to weight loss.