An unassuming inventor in Interventional Radiology at Penn, Constantin Cope, MD, was the creative mind behind countless tools and techniques used by medical professionals worldwide.

man with blue backgroundBy Rachel Ewing

According to family lore, Constantin “Stan” Cope, MD, began testing prototypes of new needles on oranges and grapefruits in the kitchen before anyone trusted him to try on a patient. Those modest citrus punctures back in the 1950s led to tools that are ubiquitous in medicine.

Cope died Nov. 6, 2016 after spending much of his prolific career in Interventional Radiology at the Hospital of the University of Pennsylvania (HUP). He led a quiet life as an immigrant physician and inventor, rarely telling his own story, even to those close to him. While virtually every clinician and medical trainee has used something that Cope invented, Cope himself is far less well known. These are the untold stories of Cope’s life and his legacy that is still unfolding.

Interventional Innovators

In May 1958, when Cope was a resident at the Veterans Administration hospital in Memphis, Tenn., he published a single-author paper in the New England Journal of Medicine describing an improved method of using a needle to insert large plastic catheters into a patient’s vein without a surgical incision. A month later, the Journal of the American Medical Association published his single-author paper about a new needle he invented to conduct minimally invasive pulmonary biopsies.

“We could put just a little anesthesia on the skin, put the needle between the ribs, and put this Cope needle in, and pull out a piece of tissue without any complication,” recalled Abass Alavi, MD, GME’70, a professor of Radiology at HUP who was a newly arrived Persian immigrant and medical intern in 1966 when he met Cope at Albert Einstein Medical Center. “That is a genius approach. And he was the person who imagined it.”

An internist recruited to work in Radiology at Einstein on the merit of his inventions, Cope was a central figure among the radiologists who were revolutionizing their specialty in Philadelphia in the 1960s. These local innovators converged in a group called the Philadelphia Angio Club that helped to expand radiology beyond its origins using radiation to create images that visualize the body’s interior, into the earliest procedures of interventional radiology, combining imaging with minimally invasive procedures to address illness or dysfunction by inserting catheters, wires, and coils in imagery-guided techniques.

family smiling

The Cope family at home in the 1960s.

“He was the only nonradiologist in this group, as a matter of fact,” recalled Stanley Baum, MD, GME’61, an emeritus professor of Radiology at HUP who chaired the department for more than two decades. “Everyone respected him for his unique ability to see a problem and go in his office and create a gadget to solve the problem.”

Catheters and other tools were not widely available at the time because the field was so new—so Cope made them using materials he purchased at hardware stores and the Army/Navy supply shop.

Curious about medical imaging and angiography, Alavi sometimes attended these Philadelphia Angio Club meetings. Cope brought an engineering mindset to bear on helping patients—ultimately an inspiration for Alavi’s own path branching out beyond on-on-one clinical care to innovations that affect millions. (See sidebar, “As an Innovator, You Deal with the Universe”)

The founding members of the Philadelphia Angio Club went on to form the Society of Cardiovascular and Interventional Radiology a decade later. Now called the Society of Interventional Radiology, it is a premier professional organization in the field.

After their paths diverged for a time, Alavi, Baum, and Cope reunited at HUP in the early 1980s, where they would work together for the next three decades. Alavi and Cope rekindled what became a lifelong friendship. Yet the reticent Cope spoke of his own life so little that Alavi never knew that Cope, too, was an immigrant.

illustration of an invention

As an Innovator, You Deal with the Universe

diagram of a body

The first whole body tomographic scan, produced by Alavi in 1976, used fluorodeoxyglucose with fluorine-18 (FDG-18). "This is very much like the first picture that Roentgen took with X-ray of his wife's hand," Alavi said. An outline of the body is superimposed for clarity.

A young Persian physician from a humble background, Abass Alavi, MD, arrived in Philadelphia in 1966. Raised on 50 cents per day and studying by the light of a kerosene lamp, Alavi had toiled for years to become a doctor to ease the soul of his father, who died after suffering six months with untreated gangrene.

But when Alavi came to America, some of the other doctors were obnoxious to him. “I didn't speak well,” he recalled. “My medicine was old-fashioned French medicine.” Visiting the Radiology department at Einstein, Alavi found that Cope was kind to him, however—and more than just kind. “His creative mind and thoughtfulness were a source of inspiration for me,” he said.

Cope helped Alavi see a way forward to fuse his mission as a healer with his lifelong passion for the physical sciences, overcoming the frustration he’d felt with the limitations of treating only one patient at a time. “As an innovator, not only you deal with that one person, but you're dealing with the universe,” Alavi said. “This is why methodologies that Stan has introduced are being recorded in the history of medicine. It's not one person who comes to somebody's office and gets some medication or surgery in the operating room. It applies to thousands, millions of people.”

Over the years of his friendship with Cope, Alavi took a parallel track, using molecular insights to pioneer new procedures in nuclear medicine. Today, Alavi serves as a professor of Radiology and Neurology at Penn’s Perelman School of Medicine, as well as director of research education in Radiology.

In the 1970s at Penn, working with tomography pioneer David Kuhl, MD’55, GME’59, neurologist Martin Reivich, MD’58, GME’63, and investigators from the Brookhaven National Laboratory, Alavi was a member of the first group in the world to obtain tomographic images of the brain and scans of the whole body. Alavi went on to make numerous research findings in single photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI).

PET makes it possible to see the earliest molecular changes that are the basis of disease, showing disease activity that CT or MRI alone cannot provide—enabling earlier diagnosis and rapid treatment monitoring for numerous diseases. These imaging techniques are already used in diagnosing millions of patients worldwide each year with dementia, brain trauma, schizophrenia, and other disorders. For example, PET can help diagnose Parkinson’s disease 10 years before a patient shows symptoms. The technology also sometimes helps prevent unnecessary surgery, evaluate a patient’s response to cancer drugs, and influence treatment for brain disorders, inflammation, infection, and many other disorders. Alavi is currently working on using PET imaging to study atherosclerosis and heart disease. 

“My colleagues and I are conducting research based on logic, bringing science to medicine,” Alavi said. “This is really what has been my mode of operation over the past 50 years in the United States. Combining powerful imaging modalities, we will continue to change the way clinicians treat some of the most common problems of mankind and reduce human suffering for many years to come.”

—Greg Richter and Rachel Ewing

Personal History

Cope was the only surviving child of Polish Jewish émigrés in Paris, born in 1927. Aron Kope, formerly Kopelowicz, worked as an engineer and activist while seamstress Esther Kope dressed fashion models in the family’s apartment. (Cope changed his name’s spelling when he entered the U.S. as a young adult.) Both Esther and Aron had lost most of their family to the pogroms—murdered or starved by the lack of work or migration opportunities. The few relatives who survived in Poland at the time of Cope’s birth later died in the Holocaust.

Attuned to the shifting political winds, Aron Kope moved his young family to escape the mounting Nazi threat before the war reached them in France. It met them in London instead. Cope later recalled spending time in his abandoned city apartment building, throwing things out of the windows onto the quiet city for fun.

“It was a big adventure and nothing was scary about it to him,” Cope’s daughter, Evelyn Stainthorpe, recalled. “He reminded me of Mr. Magoo, including his driving. He kind of just wandered through life with everything crashing all around him, yet unaffected by it all.”

Cope gained admission into a medical college in England and later transferred to a U.S. medical school to be near his parents; Aron had moved years earlier for his Jewish Revisionist political work in New York and Esther joined him after the war. As soon as he gained citizenship, Cope was sent off to the Korean War but was lucky to land in a lull in the fighting. He specialized in treating people injured by landmines and delivering babies.

Within a few years, Cope met and married Mary Grace Heller Cope, and the couple had five babies of their own. In 1963, Cope accepted his position at Einstein in Philadelphia, so the family settled in the suburban community of Elkins Park. They chose the neighborhood in part for proximity to some old friends of Aron Kope’s from his work in establishing Israel. Stan and Mary Cope befriended these neighbors, and their elder sons Yonatan and Benjamin (Bibi) babysat for the Cope children before they moved back to Israel. Today, Bibi’s name is well known there; he’s the Prime Minister.

Cope’s life story was not always easy for his children to extract. “He was not a storyteller,” said Connie Cope Franckle, his younger daughter. “Not, ‘Let me tell you this or that.’ You had to by chance ask the right question, and then you would get the story.” More than 20 years would pass between the night when Esther Kope, on her deathbed, confessed one last story to her son, and the day when someone happened to ask the right question to hear it. (See sidebar, “An Undiscovered Early Chapter”)

Living his modest life, Cope was an avid tennis player, a violinist in the Chestnut Hill orchestra, and a family man who loved Peter Sellers and silly jokes. Each morning, he ate a soft-boiled egg. In the evening, he watched Jeopardy! with Mary. In between, when he wasn’t working at the hospital, he tinkered with his prototypes.

“At home when I was growing up, I would hold a lighter under his catheters so he could stretch the catheter,” Stainthorpe said. “I never knew what he was doing. There were always drills and all kinds of stuff lying around the dining room table.”

Tools of the Trade

“I can’t even begin to tell you how many things he basically invented,” Baum said. “Catheters, guide wires, new approaches to difficult problems.”

Cope was a prolific inventor even within a specialty that prides itself on creativity. “Our field is about innovation,” said Richard Baum, MD, GME’93, chief of Angiography and Interventional Radiology at Brigham and Women’s Hospital and son of Stanley Baum. Surgical specialties, Richard Baum continued, might encompass 10 procedures each. “In interventional radiology, there are well over 100 types of procedures we do.” Many of the procedures that originate in interventional radiology ultimately become part of other specialties, he noted.

Indeed, many of Cope’s inventions have become ubiquitous in medicine worldwide, thanks in large part to Cope’s friendship with William Cook. When the two men first met at a medical conference and began discussing ideas about new equipment, Cook ran a small manufacturing company with his wife out of their spare bedroom in Indiana. Cook went on to manufacture tools based on Cope’s ideas.

Today, Cook Medical is a major international medical device and supply company that manufactures thousands of products, dozens of which—including entire product lines used in fields from gastroenterology to neurology—owe their origins to Cope. Many of Cope’s concepts have been copied or modified by other companies.

The locking Cope loop, for example, is so common that it is often sold generically. Before its invention, doctors who inserted a catheter to drain excess fluid from an organ ran into a common problem: The catheters tended to slip out.

“Stan came up with idea to have the tip of the catheter attached to a string,” Stanley Baum said. “After the catheter was in you would pull the string so the tip of the catheter in the organ makes a curve on itself. That was a very simple thing, and in short order it became the standard of how everyone was doing this.”

Such elegantly simple solutions were Cope’s hallmark. “His genius was to work out a solution that others would look at and they’d go, ‘Why didn‘t I think of that myself? Wow!’” said Joe Roberts, vice president of corporate development at Cook Medical.

Cope’s relationship with Cook Medical allowed him to bring his ideas to the world while still keeping his hands-on work in the clinic. “He wasn’t really interested in the royalty stream and starting companies,” said Tom Osborne, senior vice president for intellectual property development at Cook Medical. “That rules the world now. But not for Stan. He had patients in mind only.”

illustration of a tool

An Undiscovered Early Chapter

two snapshots, one of a man and woman, the other of a man

Left: Russian neurologist Konstantin Tretiakoff. Right: Aron and Esther Kope 

One evening, not long after Cope had had a stroke, his daughter-in-law asked him to tell her about his father, Aron. By chance, that was just the right question to elicit a new story. Connie Cope Franckle, Cope’s younger daughter, recalled, “Through his restricted voice, he said, ‘Aron’s not my father.’”

After the heart attack that precipitated her death in 1982, Esther Kope had told her son that his real father and namesake was a Russian graduate student in Paris. “We always wondered why [our father’s] name was Constantin. It’s pretty weird for a Polish Jew,” Franckle observed, adding that the story also explained why no one in the family inherited Aron Kope’s big nose and ears.

With little information to go on beyond the pronunciation of the Russian surname that Cope repeated that night a decade ago, his elder daughter, Evelyn Stainthorpe, went online and found a promising lead in the name and photo of Konstantin Nikolaevich Tretiakoff. “No one in my family has my father’s nose,” Stainthorpe said. “This man has my father’s nose.”

Tretiakoff was a famous Russian doctor credited for discovering and naming the Lewy bodies in the brain that are a hallmark of Parkinson’s disease, in his 1919 dissertation. According to a historical account published in the journal Movement Disorders in 2008, Tretiakoff left Russia because his family’s democratic leanings placed them at risk of persecution from the Tsar, and his citizenship was revoked. After he completed his medical and scientific training in Paris, he worked in Brazil for several years in the 1920s before returning to western Europe for a time. According to this account, Tretiakoff returned to Russia once his citizenship was restored. He later became the founding chair of Neurology at the Saratov Medical University and had a distinguished career.

As part of her search, Stainthorpe enlisted her Penn Radiology colleague Maxim Itkin, MD, to use his Russian language skills to try to make contacts—initially to no avail.

But her hope of finding answers persists. In March 2017, Itkin received an email from the head of Neurology at Saratov Medical University requesting information about Tretiakoff for a symposium in honor of his 125th birthday this year. Itkin and Stainthorpe both wrote back and hope the connection will grow. Tretiakoff had a daughter in Saratov, Stainthorpe said, but they have not made contact to discuss DNA testing to learn if Tretiakoff was truly Cope’s father.

If he was, they know this: If Tretiakoff left Paris for Russia as reported in September 1926, Esther Kope would have not yet known she was pregnant. Constantin Cope was born June 3, 1927.

The Quiet Genius

stan and mary smiling

Stan Cope with his wife, Mary Grace Heller Cope, in 2003.

Cope never stopped inventing, even up to his retirement. One of his later innovations made a strong impression on a young Russian-Israeli radiologist, Maxim Itkin, MD, GME’02. “’Look at this, complete science fiction, they can intervene on the lymphatic system,’” Itkin, now an associate professor of Radiology and Pediatrics at Penn, recalled saying when he first read about thoracic duct embolization.

Itkin didn’t know that the man who invented this minimally invasive procedure was on the faculty at HUP when he arrived for his fellowship shortly thereafter, but he quickly seized on his good luck. He asked Cope to teach him this new way to intervene on a system that had been an obscurity in medicine for generations. The lymphatic system is a low-pressure circuit flowing throughout most of the body, transporting cells and proteins from organs and tissues in a colorless fluid. Patients experience shortness of breath and fluid in the chest if the largest lymphatic vessel, the thoracic duct, is severed or damaged—a surgical complication that lacked any useful intervention before Cope’s. Cope figured out how to see the thoracic duct well enough to know where it was leaking, and he determined a way to insert a tiny catheter to push still-tinier tools through that catheter to seal the leaks.

“Who would think of being able to catheterize a thoracic duct? The thoracic duct structure is like a thin piece of spaghetti,” Stanley Baum said.

Watching in silence during lymphatic procedures that could last eight hours, Itkin assisted while the taciturn Cope offered few words of instruction or commentary—but even this silent modeling laid the groundwork for innovations that are still unfolding. (See sidebar, “Just a Matter of Plumbing”)

Even though Cope rarely boasted—or even spoke—of his accomplishments, his genius for elegant and unexpected solutions continually impressed those around him. He opened new possibilities in new fields across the medical landscape, and he inspired younger physicians who learned alongside him—Alavi, Itkin, and Richard Baum, among others—to each innovate in surprising ways.

“I remember when I was a kid, I went to the circus. The most impressive thing I saw was a man who was able to stay balanced on a ball with his finger,” Stanley Baum said. “The remarkable thing wasn’t that he was able to do that. It was that he was able to think that he might be able to do that. That’s what Stan Cope was like. He would do things nobody would ever think possible.”

“Just a Matter of Plumbing”

rubber casts

Patients with plastic bronchitis cough up rubbery casts in the shape of the body's bronchial tubes.

When Maxim Itkin, MD, began to learn from Cope, he asked a big question: How do you invent things?

“He said, ‘Oh, it’s easy. You just read old literature. All the ideas are already there,’” Itkin recalled—and he pointed to a pile of old books on his desk about the lymphatic system. “Everything I am doing right now has been not exactly known, but the ideas, the concepts, are out there.”

A vast quantity of knowledge about the lymphatic system from the past century has been largely forgotten because it was never translated from animal studies to humans, Itkin said. Useful methods of visualizing the lymphatic system in a living person didn’t exist. “When you image, you can understand, and then you can intervene. That’s why we became so successful.”

Itkin began by learning thoracic duct embolization from Cope. As Cope neared his 2004 retirement, Itkin began to take over performing this procedure. Only small handful of Cope’s trainees, including Richard Baum, MD, learned the technique.

After learning about lymphatic intervention from Cope, Itkin has since made dramatic improvements in lymphatic imaging by joining forces with the Children’s Hospital of Philadelphia (CHOP) radiology and cardiology departments in developing magnetic resonance lymphangiography. What was once an invisible network of fluid vessels has become vivid in fine detail.

The body has many networks of tubes—the circulatory system and the bile duct to name a few—and, with advanced lymphatic imaging, “all of a sudden we have access to a set of tubes we had limited access to before,” said Baum, who is pursuing similar work at Brigham and Women’s Hospital. “Diagnosis, treatment, giving drugs—it’s a new horizon for us.”

The combined CHOP/HUP team has taken early steps toward that new horizon by treating patients with plastic bronchitis, a devastating complication that occurs in a small percentage of children who undergo surgery for right-side congenital heart failure and in other patients for unknown reasons.

“It’s just a matter of plumbing,” said Itkin, who is now director of the CHOP/HUP Center for Lymphatic Imaging and Interventions. “It’s leaking. We need to find the way to fix it.”

Plastic bronchitis causes a person’s lungs to repeatedly fill with fluid that hardens into rubbery casts. When coughed up, those casts, which have molded to match the shape of the bronchial passages, look like tiny branching trees—beautiful if they weren’t so often deadly. Once only treatable only with a heart transplant, plastic bronchitis was usually a near-hopeless condition if it didn’t subside naturally, until Itkin and Yoav Dori, MD, PhD, a pediatric cardiologist at CHOP, pioneered these methods to intervene. Dori, Itkin, and their colleagues reported in the journal Circulation last year on the imaging of their first 18 pediatric patients with plastic bronchitis. Fifteen of the 17 patients who received an intervention to seal lymphatic leaks thus visualized had significant symptomatic improvements that were sustained months later. The team subsequently reported similar success in adult patients in the Annals of the American Thoracic Society

Itkin and his colleagues are working to extend this impact to numerous other lymphatic conditions, both known and unknown. Itkin is confident that within five years, lymphatics will be widely seen as a new subspecialty in medicine. Indirectly, it would be the second specialty that owes its origins in large part to Cope.

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