The animal’s upturned belly glows from within, as if red hot, while shadows crisscross furtively beneath the skin. “There’s your scope,” one surgeon says to another, gesturing toward a video monitor tracking the progress of this intra-abdominal game of hide-and-seek.

There are two scopes in this pig’s belly—one a fixed-tube laparoscope peering in through a tiny incision cut into the lower abdomen, the other a flexible endoscope which has entered the animal’s body through its open mouth and then snaked its way into its upper abdomen.

The writhing black endoscope is operated by Sergey Kantsevoy, one of the driving trailblazers in a radical new idea. His journey into the peritoneal cavity is being watched intently through Michael Marohn’s more rigid laparoscope. The heads of both scopes, which employ their own video probes and monitors, will momentarily greet each other face-to-face, so to speak, without any abdominal tissue coming between them. This will be a rare medical moment in its own right, but not the main reason for the attention paid by 11 other GI colleagues who check in throughout the day. They are waiting to hear if this procedure will achieve a key threshold in the maddening conundrum that has eluded them for more than five years.

For these GI surgeons, this is pig number 49 in an accelerating quest to see if they can use the flexible endoscope to enter the body through a natural orifice such as the mouth and then penetrate the outer boundary of the intestinal tissues—the gastric wall within the abdomen. Once there, they hope to operate, withdraw from the surgical site and—of overwhelming importance in today’s experiment—make an airtight seal over the hole so no bacteria can seep through. They then will slip the scope back out without leaving a trace that they were ever there. If their big idea works, they believe it could usher in a new, more ideal kind of GI surgery. Rather than slicing into a patient’s abdomen from the outside to reach damaged organs, surgeons would enter the body without a single cut through the skin or muscle.

But a fundamental question remains: Beyond the obvious cosmetic value, what’s the point?

> SCOPE MEETS SCOPE: To observe the experiment, a laparoscopic surgeon captured live video of the endoscope’s progress. Each instrument had its own monitor—endoscopic image on the left; laparoscopic on the right.

The fact is, from the day surgeons first began cutting into the human body to make repairs, they have struggled with the consequences of slicing through skin and muscle and sawing through bone to gain access to internal organs. These large “open” operations place a heavy burden on human systems, disrupting organs, creating new pathways for infection and demanding long recovery times.

Twenty-five years ago, a solution seemed at last to be at hand with the introduction of the laparoscope. This new elongated tool, guided by a camera on its tip and images on a nearby monitor, required but a few tiny incisions in the skin as it maneuvered toward tissue targets. Its minimally invasive procedures made for quicker healing times and fewer obstacles. Patients warmed to their smaller scars.

Over the next few decades, gastroenterologists made great headway, first with the laparoscope and later with the new flexible endoscope. This second amazing tool required no incisions at all. It simply entered the body through the mouth and then cleverly wound its way into the esophagus, stomach, intestines and colon, where specialists became adept at examining, snipping, rearranging, suturing and excising unwanted tissues.

Now, only one seemingly impenetrable barrier remained for the endoscope to be able to reach every part of a GI surgeon’s realm: Organs like the appendix, gallbladder, liver, uterus and ovaries lie beyond the gastric wall. Perforating that border would mean crossing an area crawling with bacteria—an open invitation to infecting nearby sterile organs. In laparoscopic and open procedures, surgeons carefully maneuver around the gastric wall to avoid such risks, but the flexible endoscope would need to breach that wall to reach the organs behind it. To most, that seemed like an open invitation to a deadly case of peritonitis.

Still, by 1997, one prominent endoscopist had started thinking seriously about tackling even this challenge. Early that year, Tony Kalloo, a rising star in gastroenterology who’d just become Hopkins’ director of endoscopy, accepted an invitation to speak at an annual meeting in San Francisco. As he ruminated about his presentation, Kalloo began thinking out of the box. By the time he took the podium, he had prepared an elaborate series of slides outlining a notion by which GI surgeons would operate without any external cutting at all. They would enter the body through a natural orifice and wind their way to the gastric wall, penetrate it and manage all the sterility issues.

If laparoscopists could now take out gallbladders and return patients to work up to three days later, Kalloo’s thinking went, performing those same operations with the endoscope through the body’s natural openings would make for scar-free appendectomies, easier gallbladder removals, smarter gastric bypasses, smoother tubal ligations—all with even shorter recoveries, less pain and no external scarring whatsoever.

The audience listened politely. Then a few chuckles erupted. What was Tony Kalloo thinking?

From the video monitor for Michael Marohn’s laparoscope, the glowing head of Sergey Kantsevoy’s endoscope can be seen behind a diaphanous layer of tissue. “See the bubbles?” Marohn asks with a certain urgency. “Sergey, look at my monitor a second. That’s your probe, right there.”

Kantsevoy’s face is a study in concentration as his enormous gloved hands expertly manipulate a cluster of knobs at the probe’s base to guide its tip through the complex web of tissues. In the darkness beyond the surgical lights, an observing surgical fellow mimics his hand motions, like a shadow-boxer.

Then the unveiling: The head of Kantsevoy’s squirming endoscope pops into the open just below the lower stomach wall, naked under the spotlight of Marohn’s video probe. Seemingly of its own accord, the endoscope’s head pirouettes in three dimensions, unsheathing its glistening forceps and scalpel in a boastful display that heralds an entirely new frontier of medical possibilities.

“So this is scope meets scope—laparoscopy meets endoscopy,” Marohn says as he observes Kantsevoy’s end-zone dance. For laparoscopic surgeon Marohn, the arrival of this new contestant on his traditional playing field might, at first blush, portend a turf war. But the spirit of discovery is contagious in its own way, and Marohn is happy to bring his skill set to the chase. This occasion could also capture a pivotal solution to one more obstacle in GI surgery.

Kalloo and his fellow researchers are all too aware that it won’t be enough to show that they can enter the extra-abdominal cavities and perform marvelously sterile procedures. They must also come up with a way to patch the hole in the transgastric wall so that it’s airtight. There can be no leaks. The abdominal wall is notoriously tough territory. Common sutures and clips have proven unreliable.

This last major hurdle has dogged these surgical researchers through hundreds of tries. Now, experimental technology that has been assembled in a briefcase-size console tucked just behind Kantsevoy could solve the problem. Kantsevoy and another endoscopist test the new device in preparation for deployment. When they maneuver the tip of their endoscope closer to the hole they’ve made in the gastric wall, a robotic female voice emanates from the aluminum control box behind them: “In firing range.”

The consulting bioengineer cranes his head and intones, “This is history.”

> THE VISIONARY: Trailblazing endoscopist Tony Kalloo first proposed the new form of surgery.

When Tony Kalloo recruited Sergey Kantsevoy to work with him in 1997, it was a calculated pairing. Kalloo, who graduated from medical school in his native Trinidad in 1979, had narrowed his interests to the specialty of gastroenterology during residency and fellowship training at Howard University and Georgetown. Endoscopic surgery was just taking off during those years, and a mentor helped him quickly master the new technology. But for all of Kalloo’s skill with the endoscope, he never kidded himself about whether that instrument could handle heavy surgery: Whenever he detected a trace of disease in an abdominal cavity beyond the gastric wall, Kalloo always asked a trained GI surgeon to step in.

And so, as he embarked on his bold transgastric idea, Kalloo knew he needed a GI partner with cutting smarts. With Kantsevoy, he would have just the man—a hard-working Russian émigré who’d trained in Gorky as a surgeon but migrated into gastroenterology soon after coming to America in 1992. In 1997, when Kantsevoy came to Hopkins in search of a GI fellowship, he closed out his “three-minute interview” with Tony Kalloo by making a pledge: “You will not regret this.”

One of the pair’s first major hurdles came in the form of chilly objections from an industry partner that Kalloo had sought as a funding source. Olympus Optical, the cautious Japanese maker of cutting-edge endoscopic equipment, threatened to withdraw from its relationship with Kalloo if he persisted on this “drastic” and “impossible” transgastric course. Even after Kalloo had shared promising results from early experiments at an international presentation in 1999, Olympus maintained its opposition. To fund his studies for the first years, Kalloo would rely solely on his division’s research budget.

Medically, Kalloo’s first great obstacle was to preserve sterility throughout the abdominal region. Early experiments soon hit on a successful answer: flushing the stomach with an antibiotic solution before perforating the gastric wall. Word of that breakthrough won a small cult of believers for the new GI approach. Dozens in the United States and overseas joined the pursuit.

Few of these early experiments in animals saw publication. Finally, though, in 2004, Kalloo, Kantsevoy and other key associates published a seminal study in Gastrointestinal Endoscopy proposing endoscopic transgastric surgery as “a new approach to diagnostic and therapeutic interventions.”

Within months, Kalloo learned that a GI specialist in India had begun experimenting with the new endoscopic procedures on humans. The following year, that surgeon came to an international gathering of endoscopists and announced that he’d performed 20 successful appendectomies and a handful of tubal ligations using the transgastric technique—all, reportedly, with no incidents of infection.

With momentum building, Kalloo joined a coalition of select scientists who shared the vision. They named their approach “natural orifice translumenal endoscopic surgery,” or NOTES, and they dubbed their group the Natural Orifice Surgery Consortium for Assessment and Research, or NOSCAR. The researchers trademarked the term and set up a Web site, www.noscar.org, that would act as a clearinghouse for the latest developments. Today, what stands out on the site is the fact that Olympus has done a 180-degree turnabout: A prominent item proclaims that the firm is offering a $500,000 grant to innovators in the field. So far, the funding dollars have attracted 84 applications from around the world.

And yet many prominent surgeons remain doubtful that GI operations can ever truly be safe without external cuts. “It’s fraught with dangers,” one eminent member of the profession proclaimed in a recent commentary to the BBC. “There are more dangers going through the stomach lining than doing laparoscopy.” Another highly regarded specialist, meanwhile, opined in the same report: “You would have to seal up the hole you’ve made in the stomach as you come out and then make sure that hole doesn’t leak.”

Ah, yes: The hole, transgastric surgery’s last major hurdle.

“In firing range” warns the robotic voice, as Sergey Kantsevoy homes in on the perforation he has made into the digestive tract of pig 49. Kantsevoy withdraws his scope and moves it closer to the perforated tissue again, prompting the voice to repeat, “in firing range.”

The bioengineering consultant standing at Kantsevoy’s side guides him and his colleagues in the maiden deployment of this very space-age endoscopic suturing device, which at this moment is extending its experimental probe. As Kantsevoy and an associate endoscopist, Samuel Giday, delicately coordinate the approach, Kantsevoy maneuvers the endoscope’s position. Giday, meanwhile, manipulates the scope’s forceps and the prototype stapling device that extends from its head. It is the staple gun they will use to seal off the hole made by the endoscope in the pig’s stomach.

> SURGICAL PARTNER:Sergey Kantsevoy brought the combined specialties of surgery and endoscopy to the experiments.

Kantsevoy and Giday gather in a clump of the perforated tissue, looking for a suture line. Laparoscopist Marohn advises. “You need a bigger bite,” he says. “Take a bigger bite.” Then, with the tissue gathered up just so, Giday hits the stapler’s trigger. In both video monitors, a sparkle of light flashes across the targeted tissue. In the blink of an eye, a series of titanium sutures has instantly deployed across the 6-centimeter expanse of gastric tissue, “like magic,” says Kantsevoy.

The seal looks good through the monitors, but will it hold?

The physicians deliberate as one laparoscopic master weighs in with a voice of optimism. “This has promise,” Mike Marohn says.

There are days when Tony Kalloo pauses and catches his breath. Like today, amid a schedule crammed with meetings and patient consults, when his assistant hands him the sheets of slides from his bold presentation in San Francisco 10 years ago. Suddenly, a curiously boyish awe steals across his face. He raises the slides over his head to study them, leaning back in his office chair, drifting off into an unselfconscious silence. “For gosh sakes,” he finally whispers, seemingly to himself. It’s the first time he’s looked at them in years, and they bring back memories.

“It aroused such a flood of emotion,” he says, remembering the crowd of skeptics who challenged his idea that GI surgery might someday start with an endoscope being slid down a patient’s mouth. He recalls appealing to his colleagues, “Allow us to get this into the lab.”

Looking back now, the determined GI director becomes philosophical about all that’s happened since then. All the resistance to his proposal, he says, was just part of the natural to and fro of modern science. “It’s like running a marathon. It’s kind of painful along the way but in the end you know you’re going to be done.”

Ramsey Flynn is the magazine's associate editor.