In the fall of 1999, a young chemical engineer named Todd Zion left his job at Eastman Kodak to enroll in the Ph.D. program at the Massachusetts Institute of Technology.
While looking for a subject to research, Zion noticed a grant proposal, never funded, that another graduate student had written on the subject of drug delivery. One possibility mentioned in the proposal was the development of a kind of insulin that would automatically respond to changes in blood-sugar levels, becoming active only when needed to maintain healthy levels around the clock. If it worked, the sugar-sensitive version could transform the lives of the six million people with diabetes in the United States who use insulin. No longer would they have to test their blood-sugar levels multiple times per day and try to calculate how much insulin to take. The self-regulating insulin would curtail high sugar levels, which raise the risk of long-term complications, and eradicate, or at least reduce, the most dangerous short-term complication: hypoglycemia, when sugar levels fall so low that they can cause confusion, unconsciousness, seizures and even death.
“I thought, Wow, that is a really neat area in which to do research,” Zion told me. Other researchers had been trying for 20 years to make insulin work only when needed. The first to publish a study were the scientists Michael Brownlee and Anthony Cerami, who in 1979 embedded a sugar-encrusted form of insulin in a mesh pouch with a sugar-loving protein called lectin. The idea was that when blood-sugar levels were elevated, the lectin would bind to the sugar in the blood and allow the insulin to leak out; when sugar levels were normal, the lectin would bind to the sugar-encrusted insulin, keeping it inside the pouch. But the system was impractical, because the pouch would need to be implanted under the skin and periodically refilled. And the lectin, derived from the jack-bean plant, was toxic.
In his first three years at M.I.T., Zion used nanoscale molecular engineering to create an insulin-lectin gel that could be injected without the need for an implanted pouch, while also rejiggering the lectin to make it less toxic. “It worked great visually,” he said. When the gel was placed in a sugar solution, “you could see the outer edge getting clear and dissolving . . . almost like an ice cube melting in water.”
The problem was that, no matter how hard he tried to manipulate the gel, the insulin either leaked out too easily, even when sugar levels were low, or not easily enough, when sugar levels were high.
Zion knew there was another approach: changing the insulin molecule itself, to make it sensitive to blood-sugar levels directly. But, he said, “almost everyone in the field of drug discovery believed that you should never, ever change the insulin molecule. . . . From a regulatory point of view, as soon as you manipulate the molecule, you’ve created a new drug. It doesn’t matter if you’ve attached a single atom to it.” Doing so, he knew, would require years of clinical trials in preparation for a new-drug application submission to the F.D.A. “That’s the only reason people were afraid.”
Zion’s trick was to attach a chemical arm — a short chain of sugars — directly onto the insulin molecule. (Attaching sugar to insulin? “Yes, it is a bit ironic,” he concedes.) The beauty of this approach is that it permits the insulin to latch directly onto the sugar-loving lectin in the gel — but only as needed. When blood-sugar levels are high, the lectin hooks up with any sugar floating freely from the blood, allowing the insulin molecule to do its normal job of connecting with insulin receptors on the surface of cells. (That is how insulin lowers blood-sugar levels, by merging with a cell’s insulin receptor and unlocking the cell membrane to allow sugar in.) When the sugar gets swallowed up by cells, lowering levels in the blood, the only remaining sweet for the lectin to attach to is the altered insulin’s sugar arm. Handcuffed to the lectin, the insulin can’t bind to insulin receptors. And so the insulin stops working to lower blood-sugar levels precisely when it’s no longer needed, because its sugar chain is held hostage by the lectin.
Zion called his new chemical creation smart insulin. In 2003, after testing it in rats, he won M.I.T.’s annual Entrepreneurship Competition. With the $30,000 prize money, he started a company called SmartCells and tried to see if he could make it work well enough to test it in humans.
The Latest on: Inventing drugs
via Google News
The Latest on: Inventing drugs
- Trump’s Virus Treatment Revives Questions About Unchecked Nuclear Authorityon October 11, 2020 at 4:47 pm
Even before the president was given mood-altering drugs, there was a movement to end the commander in chief’s sole authority to launch nuclear weapons.
- The detective who obtained the search warrant cited the deliveries to falsely implicate Taylor in drug trafficking.on October 9, 2020 at 3:10 pm
The detective who obtained the search warrant cited the deliveries to falsely implicate Taylor in drug trafficking.
- Development of precision drug delivery tool to treat traumatic brain injuryon October 7, 2020 at 5:42 am
An interdisciplinary team of researchers at the University of Southern California has developed a precision drug delivery tool to selectively treat areas of the brain damaged during a traumatic brain ...
- Concentrating and Releasing Drugs in the Brain with Pinpoint Accuracyon October 5, 2020 at 1:00 pm
Scientists at ETH Zurich say they have developed a technique for concentrating and releasing drugs in the brain with much accuracy. This could make it possible in the future to deliver psychiatric and ...
- A new method to deliver drugs to the brain with pinpoint accuracyon October 5, 2020 at 10:17 am
Focused ultrasound waves help ETH researchers to deliver drugs to the brain with pinpoint accuracy, in other words only to where their effect is desired. This method is set to enable treatment of ...
- Millimetre-precision drug delivery to the brainon October 5, 2020 at 9:47 am
Researchers at ETH Zurich have developed a method for concentrating and releasing drugs in the brain with pinpoint accuracy. This could make it possible in the future to deliver psychiatric and cancer ...
- Covid-19 drug trials begin — but no one qualified to approve treatmenton October 4, 2020 at 10:43 pm
As the world scrambles to put the pandemic behind us, clinical trials for a coronavirus vaccine have been initiated in Pakistan as well. However, no institution in Pakistan is qualified to approve or ...
- IPAB quashes revocation of Novartis patent for anti-cancer drug Ceritinibon October 2, 2020 at 1:15 pm
Natco filed a post-grant opposition against the patent on September 26, 2017, on grounds of obviousness and lack of inventive step.
- Standigm and SK holdings C&C Release an AI-Based Target Identification Platform, iCLUE&ASK™, to Accelerate Drug Discovery Processon September 29, 2020 at 5:21 am
CLUE&ASK™ ( is free to the public to develop a better target prediction platform together with researchers worldwide.
- Anticancer Drugs Market Key Futuristic Top Trends and Competitive Landscape by 2025on September 28, 2020 at 11:26 pm
The geographical segmentation of the global anticancer drugs market has five key segments viz. North America, Latin America, Asia Pacific, Europe, and the Middle East and Africa. Of these, the ...
via Bing News