Proving the need for patience in medical research
In the not-so-distant past, if you were a young physician working in a cardiac catheterization lab, you would spend seemingly endless amounts of time pressing with your thumbs as hard as you could into patients' legs. For 45 minutes to an hour. For each patient.
It was a primitive conclusion to a modern medical procedure. First, a catheter was inserted into the artery, just below the patient's groin, and carefully threaded up to the site of an arterial blockage, removing the blockage to restore blood flow to the heart. The catheter was then pulled back out. At that point, the standard of care became brute force, with the clinician pressing mightily on the inside of the patient's thigh until a clot formed.
And there was more: The patient would have to spend a long, uncomfortable night in the hospital, ordered to lie very still on his or her back lest the clot break and send blood gushing into the leg. Or up to the ceiling.
So one afternoon in 1990, Indiana University School of Medicine physician Keith March decided enough was enough.
"I remember very vividly coming back to my office after doing many of these and thinking to myself, there has to be a better way," March recalled.
Eventually, he came up with one: a device, now called the Closer, that stitches up the opening in the artery where the catheter was inserted. It sounds simple, but it's not, if for no other reason than you can't see what you're doing when you're stitching.
March, now the Cryptic Masons Medical Research Foundation Professor of Vascular Biology and Medicine, was in his first year on the IU School of Medicine faculty. With a research interest in vascular biology and a knack for biomedical engineering, he was well-positioned to start work solving the problem, turning it into a side project in his lab.
The target was an opening, more like an incision than a hole, about 1.5 to 3 millimeters in length. Sewing wasn't the first option March and his colleagues tried. There were biological glues. There were biodegradable polymer plugs. They considered using radiofrequency waves to cauterize the opening closed. All seemed like good ideas, but they didn't work.
Then there was sewing—which was, after all, the standard way to close any surgical wound. In the lab, with actual blood vessel models, it was clear that with just two sutures, the closing was great, and even one was enough to significantly slow the blood flow.
But that was in the lab. In a human being, "we thought, how do we put a sewing machine at the end of a catheter and sew the hole closed, when we couldn't see it?" March said. "We couldn't sew the needle in. We had to sew only the artery, not fat or skin or muscle. We had to be able to grasp one but not both sides of the artery—we certainly didn't want to sew the artery closed."
So lots of models began appearing in the lab, made of such advanced materials as straws, paper clips, and string. After a year of experimentation on many levels, a prototype was developed, followed closely by a patent in 1994 and a decision to license the technology to a California company, Perclose. Perclose continued development, tested the device in Europe, and eventually won U.S. Food and Drug Administration approval in 1999.
"From concept to reality, it was nine years—that's an important story about the need for patience in medical research," said March.
For IU, the Closer has been a financial success: From fiscal year 2000 through 2015, it was the highest-running royalty earner of all products licensed through the Indiana University Research and Technology Corp. Total revenue has exceeded $20 million.
March likes to reflect on the Closer as a device that has helped more than eight million patients.
"Instead of helping only those patients one can directly serve," he said, "through this invention, we have helped more patients than any of us could ever see in a lifetime."