Monday, May 16, 2011

Physics in Medicine

By CARL ZIMMER
Published: May 16, 2011

DURHAM, N.C.—The sign on the door at the renovated tobacco warehouse reads “Physcient.” Inside are a few rooms that, depending on where you look, seem like an artist’s studio, a machine shop or a natural history museum. A lathe stands next to a drill press; along other walls are vises, huge enamel-red C-clamps, microscopes and plywood frames covered in electronics. But there are also reed-woven sculptures of insects called water boatmen hanging on the walls, along with glass-fronted boxes holding preserved flying dragon lizards. Casts of human rib bones are scattered on tables. A huge cast of a fearsome pair of fish jaws rests on a row of books.

Physcient is, in fact, a medical technology company. But its décor speaks to the exceptional careers of its co-founders, Hugh Crenshaw and Charles Pell. They both got their start studying biomechanics — how creatures fly, swim and crawl. Mr. Pell built models of muscles and fish heads. Dr. Crenshaw earned his Ph.D. figuring out how single-celled creatures swim. And over the past 20 years they’ve profitably translated their understanding of biomechanics into inventions, from robotic submarines to pill sorters.

Now they’re turning their attention to the world of surgery. The instruments that surgeons use today, they argue, were invented before biomechanics became a mature science. They work against the physics of the body, instead of with it. “The technologies remain remarkably unchanged,” said Dr. Crenshaw. “Maybe we can do better.”

Dr. Crenshaw and Mr. Pell are starting with a kindler, gentler rib spreader. Surgeons often treat the broken ribs and other painful side effects of open heart surgery as inevitable. But Dr. Crenshaw and Mr. Pell have invented a new kind of rib spreader that takes into account how bones can bend, rather than break. Their preclinical studies on pigs suggest that it causes far less damage.

If it turns out to work as they hope, the inventors will turn their attention to other tools of the trade. “The entire surgical tray is going to be transformed,” said Mr. Pell.

As a boy, Mr. Pell was, in his words, “a congenital geek.” He spent his free time building rockets, cars and wave machines. He went to art school and earned a master’s degree in sculpture, but his sculptures were more like robots than marble busts. After graduate school, Mr. Pell headed for California, where he ended up director of research and development at a company that built robotic dinosaurs for museum exhibits. He continued to come up with strange designs, like a water-filled arch that fish could swim inside to travel from one pond to another.

To figure out if a fish could physically survive the journey through a water bridge, Mr. Pell called up Stephen Wainwright, a pioneer in biomechanics at Duke University. “He said, ‘Who are you, and why are you doing this?’ ” recalled Mr. Pell. Despite his initial misgivings, Dr. Wainwright ended the conversation by offering to fly Mr. Pell to Duke for a visit. Not long afterward, Mr. Pell became the director of the BioDesign Studio at Duke.

At the studio Mr. Pell helped Dr. Wainwright and his colleagues build models to test their ideas about biomechanics, creating models of spinal cords, muscles, jaws and dozens of other animal parts. “These models can physically surprise you,” said Mr. Pell. “They can show you things that you didn’t think of before you built them.”

One of Mr. Pell’s biggest surprises came when he tried to make a simple model of a swimming fish. He built a rubber tube with a rounded front and then stuck a rod a quarter of the way down its length. When he put the tube in water and turned the rod back and forth between his fingers, it generated a wave with its tail. While making a new version of that tube, Mr. Pell accidentally nicked the tail end. That new shape, he discovered, caused the water to flow in a different pattern around the tube, creating thrust.

Mr. Pell, Dr. Wainwright and their colleagues got a patent for the design and started a company called Nekton to develop products from it. First, they turned it into a commercially successful bathtub toy. But when the Navy discovered Mr. Pell and his colleagues could get fishlike thrust from something without any moving parts, they encouraged him to get into the business of building underwater robots. Mr. Pell and his colleague at Nekton ended up making a highly maneuverable yardlong robot called the Pilot Fish.

“We started out as a toy company; we ended up as a defense contractor,” said Mr. Pell.

One of the people who encouraged Mr. Pell to go into business was Dr. Crenshaw. At the time, Dr. Crenshaw was at Duke studying a particularly tricky question in biomechanics: how microscopic marine organisms swim. Most marine creatures smaller than three millimeters and larger than 30 microns swim in a corkscrew. “It’s the most common pattern of motion in the world,” said Dr. Crenshaw.

Despite these wild spinnings, spiral-swimming creatures manage to navigate very well. To uncover their trick, Dr. Crenshaw built a tank in which he could film organisms spiraling in three dimensions. Dr. Crenshaw found that the organisms navigate by sensing the intensity of a stimulus — light in some cases, a particular chemical in others. If the organism is heading straight toward the stimulus, the level doesn’t change. If it drifts off in the wrong direction, the stimulus fades. The organism can simply change the curve of its spiral to change direction. “It’s a really simple rule,” he said.

Dr. Crenshaw and Mr. Pell discovered their obsession with biomechanics ran equally deep. “Chuck and I would literally just wind up chatting in a room somewhere, and an afternoon would disappear and the chalkboard would’ve been erased four times before we were done,” said Dr. Crenshaw. One evening they scribbled a plan on a napkin for a robot that swam in spirals.

They won another grant from the Defense Department and began to build a new robot, which they dubbed MicroHunter. It was small — about the size of a cigar — and exquisitely simple. Dr. Crenshaw and Mr. Pell put a light sensor at one end, a propeller at the other. The propeller was programmed to push the robot in a corkscrew path, which could be adjusted as light levels changed.

Dr. Crenshaw gave the robot its first test in a Duke swimming pool. He turned off the lights in the room and put a light at the deep end of the pool. Then he put the robot in the shallow end, pointing the other way. “It turned around and came back and hit the light bulb,” he said. “It was a perfect first try.”

Dr. Crenshaw and Mr. Pell helped open the way for other biomechanics experts to turn their insights into technology. Some researchers are building self-burying anchors based on razor clams. Others are adding bumps along the edges of windmill blades to mimic whale fins.

After their adventures with MicroHunter, Mr. Pell and Dr. Crenshaw moved off in different directions for a few years. Dr. Crenshaw left Duke in 2001 to work at the pharmaceutical company GlaxoSmithKline. He designed mazes of microscopic tubes, devices for testing potential drugs. Meanwhile, Mr. Pell continued to come up with new inventions at Nekton, like a rapid-fire pill-sorting robot. In 2008, the Massachusetts-based robotics company iRobot purchased Nekton for $10 million.

Dr. Crenshaw left GlaxoSmithKline in 2007 and began to lay the groundwork for Physcient. He decided to work in medical technology, hoping that his experience in biomechanics would let him spot opportunities to invent new devices. He lured Mr. Pell out of his post-Nekton retirement, and soon the two inventors found a medical device crying out for a biomechanical overhaul: the rib spreader.

Every year, surgeons use rib spreaders to open the chests of an estimated two million people, repair their hearts, and then close them back up. All the rib spreaders in use today are variations on the model invented by the Argentine surgeon Enrique Finochietto in 1936. Mr. Finochietto used a hand-turned crank to ratchet open two metal arms.

The Finochietto rib spreader gets the job done, but it can cause serious side effects. Survey had indicated that somewhere between 10 and 34 percent of patients end up with broken ribs. Nerves are sometimes crushed, and ligaments can be ripped. After surgery, some patients require heavy sedation for the pain, and their shallow breathing can make them prone to pneumonia. Even after leaving the hospital, some patients continue to feel pain for months.

“There was room for something different here,” said Peter Smith, the chief of thoracic surgery at Duke University School of Medicine and an adviser to Physcient.

Given all these side effects, Dr. Crenshaw and Mr. Pell were surprised at how little research had been done on the forces generated by rib spreaders. “We can’t understand why people didn’t measure forces on ribs the day that there were strain gauges to measure them,” said Mr. Pell.

Dr. Crenshaw and Mr. Pell collaborated with Greg Buckner, an engineer at North Carolina State University, and Dr. Gil Bolotin, chief of cardiac surgery at Rambam Health Care Campus in Haifa, Israel. Dr. Buckner and Dr. Bolotin had developed technology for sensing forces generated by rib spreaders. Physcient licensed their technology.

The Physcient team began to measure the force of rib spreading on pigs, which are biomechanically similar to humans.

They found that a Finochietto rib spreader delivered jolts of force that increased until they equaled the weight of the pig’s entire body.

“It’s almost equivalent to hanging a patient by the rib after it’s opened — just hanging them in the air,” said Mr. Pell.

“I said, ‘Well, there’s a biomechanics project if I ever saw one,’ ” said Dr. Crenshaw.

Bones may be hard, but they’re not brittle like chalk. Stretchy collagen fibers and other elastic proteins allow them to flex, like a green tree branch. Bend a branch too quickly and it snaps. But deliver the same force slowly enough, and the branch’s fibers have enough time to stretch and shift.

Dr. Crenshaw, Mr. Pell and their colleagues set out to build a rib spreader that took advantage of the physics of bone and other tissues. In their office shop, they built a prototype that was smoothly opened by a motor instead of being jerked open by a hand crank. Instead of two straight bars, they devised two rows of curved metal hooks, each of which can independently cradle a single rib or part of the sternum.

They first tested out the device on sides of pork they bought from a butcher, recording the strain on the ribs at different speeds. They noticed that a few seconds before a rib broke, they detected tiny popping sounds. These were from individual fibers snapping inside the bone. Dr. Crenshaw and Mr. Pell realized they could use these pops to avoid breaking bones.

“If you pick up a twig and start bending it, you’ll hear something snap before you ever notice any real damage to the twig itself,” said Dr. Crenshaw. “We’re doing something similar here.”

Dr. Crenshaw and his colleagues programmed the rib spreader’s onboard computer to stop advancing it within a quarter of a second after sensing one of these pops. It allows the fibers in the bones and ligaments to shift and stretch before it starts to move again.

Recently Dr. Crenshaw and Dr. Pell collaborated with their North Carolina State colleagues to test their invention, in a study financed by the National Institutes of Health and the National Science Foundation. The veterinarians opened up the rib cages of 10 live pigs — half with the new design, and half with the conventional one. It took about the same amount of time to open up the pigs with both devices. But the traditional spreader cracked ribs in four of the five pigs. The Physcient spreader broke only one rib, in the second pig the surgeons operated on, and that was caused by an accidental jam. The researchers improved the design, after which none of the remaining three pigs broke a rib.

The researchers also found that in the Physcient trials, the pigs had higher blood oxygen levels than when the surgeons used the traditional rib spreader, because they could breathe more deeply. The pigs also needed fewer painkillers, and recovered more easily.

“We hit all the important pre-clinical endpoints that we were going for,” said Dr. Crenshaw. He and his colleagues are aiming to bring their rib spreader to market in late 2012.

If all goes according to plan, the inventors want to take a look at other surgical tools that push and pull on the bodies of patients. “We’ve got years of products to bring out,” said Mr. Pell.


NYT

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