In an era of science-fiction medicine, why can’t we engineer the hormone to adjust itself?

More than 40 years ago, diabetes researchers began trying to modify insulin so that it would be released in just the right amounts at the right time, to keep blood glucose levels in a good range.

Today, there’s no such smart insulin in the clinic or apparently even in clinical trials.

Why not?

Designer insulins keep millions of people with type 1 diabetes alive and improve the health of many millions more with advanced type 2 diabetes. But to over-generalize only slightly, these folks always have the wrong amounts of insulin circulating. Too little insulin, and people are prone to nasty long-term complications, including heart and kidney failure. Too much, and they can pass out within minutes from low blood glucose levels.

So, the quest for smart insulins is still underway in labs around the world. Occasionally smart insulin expertise gets purchased by a large pharmaceutical company. Sometimes those initiatives proceed into early clinical trials. Which fail.

Meanwhile, diabetes afflicts more than 400 million people and is ramping up. The annual insulin market is at least around $30 billion. Smart insulins could grab the lion’s share and become some of the best-selling medicines in history.

Perhaps we are waiting on conceptual breakthroughs, because insulin is a famously tricky protein and a keystone of human metabolism. Perhaps only Big Pharma firms have the necessary scientific chops, clinical experience, funds and oh yeah patents to pull it off.

But really, what’s the logjam? How will it be broken?

Designer insulins Humalog, Tresiba and Novolog, courtesy Protein Data Bank.