Back When Byetta Began

Science is too big for one person working alone in a laboratory. It’s “a group effort,” as even the most recent winner of the Nobel Prize in Medicine, Andrew Z. Fire, said this week.

That’s the conventional wisdom. Yet just one person, Dr. John Eng, is responsible for the discovery of Byetta. The Food and Drug Administration approved this powerful new diabetes medication on April 29, 2005.

Already about half a million people are using it to control their blood glucose and to lose weight, myself included. At this point Byetta has taken off even faster than Lantus insulin did.

Dr. Eng certainly stood “on the shoulders of giants” as the French philosopher Bernard of Chartres said some 900 years ago. The 17th century scientist Isaac Newton, who repeated the saying, usually gets the credit for that wise phrase.

One of those giants was Dr. Eng’s mentor, Dr. Rosalyn S. Yalow, who won the 1977 Nobel Prize in Medicine for the development of radioimmunoassays of peptide hormones. After becoming an endocrinologist, Dr. Eng wanted to do endocrine research and worked in her lab at the VA Medical Center in New York for 18 years until she retired.

“The history of endocrinology is discovery of hormones,” Dr. Eng told me in April 2002 when I interviewed him for the first article ever published about the medication that became Byetta. At that time it still went by the name exendin.

“The first hormones that were discovered were those in the greatest abundance, like insulin,” he said. “In research we always want to find something new, and I am no exception.”

He thought that there might still be hormones out there waiting to be discovered. Radioimmunoassays couldn’t help Dr. Eng find them, because those assays aren’t a good way to discover new hormones. But there were other shoulders for Dr. Eng to stand on.

In the 1970s Victor Mutt and Kazuhiko Tatemoto at the Karolinska Institutet in Stockholm, Sweden found a way to isolate new hormones. They used chemical assays.

So Dr. Eng decided to use chemical assays to look for the new hormones that he thought were out there and that he so much wanted to find. But where to look?

It happened about then that Jerry Gardner’s group at the National Institutes of Health in Bethesda, Maryland, noticed reports that venom sometimes leads to pancreatitis. Since they were interested in what can cause pancreatitis, they screened a lot of the compounds of venom that can stimulate the pancreas, because overstimulating the pancreas is one way that pancreatis can occur. It was in the venom of the Gila monster, formally named Heloderma suspectum, that they found what they were looking for.

Dr. Eng read about that and thought, “Wow! That’s great.” So he ordered some Gila monster venom from a lab in Utah, as he told me when I interviewed him in 2002.

He found a sequence never before described. One of his responsibilities to science then was to name it. Since it is an EXocrine secretion that has an ENDocrINe function, he named it exendin.