Old, Brutal Surgeries

By combing through old scientific journals, medical-device companies are finding effective, but brutal treatments for common diseases that could be transformed by modern technology into safer, noninvasive procedures.

Pairing a century's worth of surgical history of glaucoma treatment with recent advances in materials design, a California company called The Foundry developed a highly engineered device that can drain fluid out of the eye just like a nasty early-20th-century procedure that involved cutting a hole in the eye.

Other diseases such as hypertension and emphysema may also benefit from modernization of antiquated surgical procedures, potentially opening up a lucrative market for medical-device companies.

"We first make sure we're looking at a very big opportunity and then look at the historical record," said Hanson Gifford, head of The Foundry, a company that invents and incubates medical devices like the new device. "Certainly looking through the medical records is a lot cheaper than going and doing a bunch of human or animal studies."

Unlike pharmaceuticals, which depend on complex intracellular interactions and can be very expensive to develop, medical devices sit on a rich and long history of manipulating the plumbing of the physical body. For centuries, anatomists and physiologists have cut into cadavers, as well as live bodies, to figure out where the heart pumps blood, which nerves connect where, and how the physical materials of the body — flesh, blood, bones — act under human interventions. They figured out a lot about the mechanics of the corpse, long before they knew anything about cells or viruses or genomes.

The Foundry's glaucoma device is based on a treatment popularized in 1906. German surgeons discovered a simple solution for glaucoma — where the eyes' lubricating liquid gets blocked, creating pressure that kills off the optic nerves: They simply sliced open a hole in the eye to let fluid drain out.

It worked, according to the medical reports of the day. The pain was tolerable — it only required cocaine and adrenal shots, not general anesthesia — but it left patients with a hole in the eye that could be made too big, dangerously reducing eye pressure, or that spontaneously closed up, eliminating its positive effects.

So the technique was abandoned, despite a 1930s review that found the procedure, called cyclodialysis (.pdf), worked 80 percent of the time when used on the right types of glaucoma.

Now, rather than physically cutting a pathway for the fluid, a newly-designed implant could act as a tiny pipe that drains fluid out from the front of the eye. This might solve the problems long-associated with the procedure — and a spin-off company has $7 million in venture capital to give it a go. The glaucoma treatment is one of a number of old, brutal surgical procedures that have been revived or modified by new technologies and materials. Inserting older materials into the body would create scarring or lead to infection, but increasing knowledge of what materials work best inside the body allows scientists to engineer new devices to solve old problems.

For example, Solx, another company working on a similar glaucoma treatment, uncovered a 1983 paper about a jeweler in the Indian state of West Bengal who had a piece of 22-karat gold (.pdf) embedded in his eye for a decade. For all those years, the gold didn't cause irritation in the eye, so Solx's scientists created a shunt out of the material.

Old medical records are particularly useful, because the problems doctors are trying to solve are old, but the amount of materials, data and knowledge that humans have accumulated about their bodies has increased.

And some of these old surgeries, which had ridiculously high risk levels, probably wouldn't be greenlighted today.

"That’s one of the good things about medical devices in general," Gifford said. "Technology rolls on but people keep getting sick from the same diseases over the ages."

And that technology has been developing at an increasing rate since medicine started to incorporate all that anatomical and physiological knowledge with the widespread use of anesthesia in the mid-19th century and antibiotics during the 20th.

"Before anesthesia, the only thing to recommend any technique was how fast it was, because you had to be able to keep the person held down and from dying of shock," said Sara Piasecki, the head of historical collections and archives at Oregon Health Sciences University's History of Medicine Library.

Without antibiotics, though, even good procedures could end up being ruined by infection, so efficacy was hard to assess. Still, human bodies have remained fundamentally the same. So much so that in time-pressured situations, like battlefield medicine, surgery hasn't changed much at all.

"We still saw off legs with a saw the way that they did back in colonial days — the way they did way back before colonial days," said Dave Lounsbury, M.D., a retired U.S. Army colonel and co-editor of War Surgery in Afghanistan and Iraq. "At the risk of being brutish, though there is fancier equipment, the procedure is fundamentally the same. Blood transfusion today in Afghanistan is identical to the way it was in World War I."

Surgery outside trauma wards, however, has been transformed by laparoscopic and endoscopic operations carried out through small incisions and enabled by fiber optics and tiny cameras.

"They are used in virtually every kind of surgery except for plastic surgery," said Dale Smith, chairman of the department of medical history at Uniformed Services University of the Health Sciences. "Almost everybody else is using scopes."

One danger of looking back to previous eras of medicine, though, is that they had far different standards for what constituted good data. Smith said that clinical-trial data collection techniques "are orders of magnitude improved."

"Evidence-based medicine is a term that was created in the 1980s," Smith said. "And medicine prior to the Second World War was really a very different activity."

Still, Gifford's team at The Foundry continues to find gold in the medicine of the past. A few years ago, they were approached by a physician-inventor talking about a radically different type of treatment for hypertension, a disease which affects about a third of the adult population in the developed world. Instead of the drugs that are currently used — and do a pretty good job for most people who can afford them — he proposed reducing the amount of nerve activity running from the kidneys to the sympathetic nervous system.

It wasn't a standard treatment, but it turned out to have deep medical roots. From the 1930s through the 1950s — before hypertension drugs became available — denervation of the area near the kidneys had successfully treated the disease.We started to track down all this historical evidence and said, 'All this is really going to work,'" Gifford said.

Of course, there were problems with the treatment. First, the surgery was brutal, and both kidneys couldn't be done at the same time. Second, too much denervation could result in the inability of the sympathetic nervous system in the lower body to do simple things like control blood flow in the legs.

A study published this week in The Lancet summed up the problems with this nasty laundry list: "prolonged hospitalization, postural hypotension, syncope, impotence and even difficulty in walking."

Perhaps, though, new technology could be used to create a kindler, gentler way of destroying nerves, without going too far.

The solution that The Foundry found is a catheter-based radio-frequency generator that is threaded up through the femoral artery and then destroys the nerves. The Foundry created a new company, Ardian, to commercialize it, and the results of the first study using the device were in The Lancet paper. It's minimally invasive and seems to have fewer side effects than the old treatment.

By killing the nerves in 45 patients with "resistant" hypertension — i.e., they don't respond well to drugs — the Ardian-funded team was able to lower the subjects' blood pressure substantially for a year. And none of the patients experienced kidney trouble or the other complications associated with the classic surgical procedure.

Michael Doumas and Stella Douma, in an accompanying commentary, call the paper "a breakthrough study," that, though more research is necessary, provides "hope for the management of a difficult clinical condition."

That hope is valuable, especially with millions of wealthy developed-world citizens walking around with untreated hypertension. Last week, Ardian raised $47 million from investors including Medtronic and Morganthaler Ventures.

While The Foundry has experienced remarkable success looking into history, there are undoubtedly more medical procedures hidden in government vaults and dusty libraries that could be mined by today's medical-device makers.

"You can look at almost any area of surgery and find techniques that were once pioneering and commonly accepted that have since fallen by the wayside for less invasive surgeries or drug therapies," OHSU's Piasecki said.

With new advances in surgical procedures, stents, shunts and pumps, some of those more invasive surgeries could be made over on their way from the library to the operating room. What might be next?

"I haven't done any research, but there was probably a surgical intervention for erectile dysfunction before there was Viagra," Piasecki noted.