Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century (29 page)

Sones's catheterization laboratory in the basement of the clinic would have looked downright medieval to twenty-first-century observers. Sones had excavated a deep pit in the floor to accommodate a six-foot-long unit designed to enhance fluoroscopic images. Looking like a submarine commander peering into his periscope, he would sit within the pit at a level below the patient, who would be laid out on the X-ray table. It was only in this manner that he could view and photograph images of the heart with the image-intensifier. Another operator would inject dye into the patient's heart chamber, carefully avoiding the opening to the coronary artery.

On October 30, 1958, Sones was working with a twenty-six-year-old man with rheumatic heart disease. His assistant inserted the catheter into the patient's artery and directed it up through the aorta into the heart with the tip of the catheter just above the aortic valve. From his place in the pit, Sones watched in horror as the tip of the catheter flipped around and dye was injected directly into the coronary artery. This was a frighteningly large amount, never imagined for use in the human heart. Fearing a cardiac arrest, he rushed out of the pit to the patient's side to be able to open his chest and massage the heart. The patient had no heartbeat for several frightening seconds. He was still conscious, so Sones asked him to cough. To everyone's relief, his heart started again, without any further complications.
⁸

The frightening misadventure taught Sones that, contrary to views held at the time, non-oxygen-carrying fluid could be injected into a major coronary artery safely. He realized he had discovered a technique for obtaining clear and detailed pictures of the entire coronary circulation. “During the ensuing days I began to think that this accident might point the way for the development of a technique which was exactly what we had been seeking. If a human could tolerate such a massive injection of contrast directly into a coronary artery it might be possible to accomplish this kind of opacification with small doses of more dilute contrast agent. With considerable fear and trepidation we embarked on a program to accomplish this objective.”
⁹
He devised a catheter with a flexible tapered tip that permitted easy direct entry.

By 1962 Sones had successfully performed selective coronary
arteriography with small doses of contrast medium—4 to 6 ml—in more than a thousand patients. Characteristically, he waited until he felt confident enough to report his clinical results with a large series. A brief paper on his technique and experience was published by the American Heart Association in its widely circulated monthly leaflet
Modern Concepts of Cardiovascular Disease.
¹⁰
Despite the enormous importance of the work, the report was written in modest style and was only four pages long. Its impact was explosive, leading to the rapid growth of the technique during the 1960s.

In 1967 Sones reported that he and his colleagues had performed coronary arteriograms on 8,200 patients, representing all types of atherosclerosis. In more than 99 percent of the cases, both coronary arteries could be seen. Branches as small as 100 to 200 microns were readily visualized.

All who knew Mason Sones were alert to his forceful and frequently bumptious personality. A small, chubby man who “swore with gusto,” his dominant characteristic was a zealous striving for perfection, accuracy, and truth. This was often manifested at medical meetings as open disagreement with a lecturer making a scientific presentation. He quickly acquired a reputation for being aggressive and even disrespectful.

One particularly memorable episode occurred at an annual scientific meeting of the American Heart Association. A slide was introduced by a guest speaker with the words, “In this normal coronary arteriogram…” He was abruptly cut off by Sones, who stood up in the back of the room and declared, “That's not normal! There's a stenosis [narrowing] in one of the coronary arteries!” Sones was correct, and similar intemperate exhibitions in his relentless pursuit of truth caused more than one public speaker to suffer some indignity. Some of this was undoubtedly because, as a pioneer, he had to fight to impose his ideas to dispel myths still defended by eminent cardiologists.

To further support his passionate struggle, Sones underwent coronary artery catheterization himself and would occasionally show his normal films during meetings to emphasize the low risk of the procedure.
Eventually, Sones developed cataracts as a result of too much radiation exposure.
¹¹
(Interventional cardiologists and radiologists now use protective eyeglasses.)

As expressed by Donald Effler, Sones's surgical colleague at the Cleveland Clinic, “figuratively speaking, Sones's catheter pried open the lid of a veritable treasure chest and brought forth the present era of [coronary] revascularization surgery.”
¹²

Once sites of blockage in the coronary arteries could be determined precisely, surgical techniques to bypass the obstruction could be devised. Blood flow could then be diverted around and beyond the obstruction to carry critical oxygen to the heart muscle.

In May 1967 Mason Sones's surgical colleague, René Favaloro, performed the first coronary artery bypass graft (which, because of its initials CABG, is referred to in medical jargon as a “cabbage”) as a treatment for angina.
¹³
The bypass is accomplished by connecting a piece of the saphenous vein, a long vein of a leg, before and after the point where a diseased coronary artery is narrowed or blocked.

Favaloro, originally from a small town in the pampas of Argentina, became intrigued by Sones's X-ray studies of the coronary arteries and spent hours looking at them. Astonishingly, he performed the first bypass without having tried it first on animals, but Favaloro explained that animal experiments are “not always obligatory.”
¹⁴
The Cleveland Clinic became a mecca for angina patients who could benefit from surgical revascularization. A number of operating suites in a newly established Department of Cardiovascular Surgery were opened.

By the time Favaloro returned to Argentina in June 1970, he and his colleagues had performed 1,086 operations with an acceptably low mortality. About 250,000 were done in the United States in 2005. These involved single and multiple bypasses with either vein or internal thoracic arteries, sometimes utilizing microsuture techniques.

Small-Scale Sewing

The development of microsuture techniques is yet another striking example of serendipity in surgery. At the University of Vermont a young surgeon, Julius Jacobson II, was asked to sever the nerves to vessels in dogs. Researchers wanted to observe the effects different drugs would have on the animals in the absence of nerves. Jacobson concluded that the simplest approach was to cut the actual blood vessels along with their accompanying nerves. Having fulfilled the goal of severing the nerves, he then faced the challenge of reuniting the minute ends of the tiny vessels or the dogs would die. But the common methods of suturing after surgery did not apply on such a tiny scale. It must have seemed like an almost impossible undertaking.

Jacobson realized that “the problem was not in the ability of the hand to do, but rather the eye to see.” With the help of a powerful microscope, he was able to suture the small vessel ends together. He described the experience as “like looking at the moon for the first time through a powerful telescope.”
¹⁵
Jacobson and a colleague went on to miniaturize conventional surgical instruments and in 1960 reported the success of their techniques in animal blood vessels as small as 1.4 mm.
¹⁶
Because Jacobson found a solution he was “not in quest of,” microvascular surgery was born.

24

“Dottering”

Once atherosclerosis could be visualized in the body and the obstructions surgically bypassed, the stage was set for working inside the artery. In the first internal approach to relieve an arterial obstruction, serendipity played a major role. In 1963 Charles Dotter, a radiologist at the University of Oregon in Portland, was examining a patient with an obstruction in a major artery in the pelvis. In performing a diagnostic catheter study by the Seldinger technique, Dotter inadvertently jammed the catheter through the site of obstruction, only to discover that he had unblocked the vessel! The potential therapeutic importance of the unexpected discovery was not lost on him.

Dotter, an outdoorsman and mountain climber, was a short, muscular, bald man whose bright darting eyes and hyperkinetic manner indicated his active mind. He was an imaginative innovator. After studies on the leg arteries of cadavers, Dotter conceived of removing obstructions gradually with a series of dilators of increasing size.

He got his chance to use his new technique for the first time on January 16, 1964. An eighty-three-year-old woman who had been bedridden for six months with early signs of gangrene in her left foot and toes due to blockage of the arteries in her leg was advised by her vascular surgeon to have her foot amputated. When she refused the operation, Dotter got his chance to prove the value of his approach. He progressively dilated her blocked artery. After the procedure, blood supply to the foot was restored and the patient was able to walk on
her own leg without difficulty until her death three years later.
¹
This technique, which came before its time, elicited skepticism in the United States as its limitations became obvious. Vascular surgeons, feeling threatened, openly ridiculed Dotter. However, European radiologists enthusiastically embraced the technique and referred to it as “dottering.”

T
HE
“C
ROWNING
” A
CHIEVEMENT
: C
ORONARY
A
NGIOPLASTY

Dotter's method of reopening obstructed arteries without surgery was the inspiration for a groundbreaking advance by Andreas Gruentzig, a charismatic young German, in coronary angioplasty. After receiving his medical degree from Heidelberg Medical School in 1964, Gruentzig pursued a postgraduate education that ranged over a variety of disciplines, including epidemiology and medical statistics, internal medicine, radiology, and cardiology. At University Hospital in Zurich, Gruentzig developed a technique that involved advancing a catheter with an inflatable balloon tip into a narrowed coronary artery (under fluoroscopic control) and inflating the balloon to compress the atherosclerotic plaque, reduce the obstruction, and enhance blood flow. Initially, he made the coronary balloon catheters in his kitchen. After successful animal studies followed by cadaver studies, Gruentzig presented his experimental results at the American Heart Association meeting in November 1976, where he was met with skepticism and derision.

Gruentzig performed the first human coronary angioplasty in May 1977 during bypass surgery through an incision made in the diseased coronary artery. After accomplishing this procedure in an additional fifteen patients, Gruentzig performed the first coronary angioplasty on a conscious thirty-seven-year-old patient on September 16, 1977, using the Seldinger approach. He reported on his success to a meeting of the American Heart Association later that year. (Mason Sones, who was in the audience, rushed toward the podium immediately after the presentation and, with tears streaming down his cheeks, embraced Gruentzig with congratulations.)
²

In a brief letter to the editor, published in the February 4, 1978,
issue of the
Lancet,
Gruentzig announced his breakthrough.
³
Word for word, the impact of this brief communication was as great as any article that had ever appeared in a medical publication. By 1979 his article in the
New England Journal of Medicine
on fifty coronary angioplasties in patients was immediately greeted as a triumph.
⁴
The medical community was by then ready to embrace the procedure—perhaps because the benefits of surgical coronary bypass had become apparent. Physicians streamed to Zurich to learn Gruentzig's procedure.

The following year, at the age of forty, Gruentzig moved to Emory University in Atlanta, where he performed approximately 2,500 angioplasties in the next five years. During this period, he was able to modify the procedure from one requiring hospitalization to one that could be performed on an outpatient basis. To demonstrate his faith in the safety and feasibility of outpatient coronary angioplasty, he asked one of his fellows to perform cardiac catheterization on him. Gruentzig jumped onto the table at 5:00
P.M
., underwent the procedure, jumped off the table, picked up his wife, and arrived for the department Christmas party by 7:00
P.M
.
⁵

Gruentzig was an exceptionally prolific contributor to the medical literature on the subject—in 1984 alone he published thirty-eight scientific papers—and helped to popularize the procedure in the United States. His stature took on legendary proportions.

Today, more than 300,000 coronary angioplasties are performed in the United States each year, and a slew of newfangled high-tech devices have rendered the once ultrarisky surgery almost ho-hum. Its further growth is virtually guaranteed by the inevitable coronary problems of the generation of Baby Boomers heading into their sixties in the first decade of the twenty-first century.
⁶

25

A Stitch in Time

Every scientist must occasionally turn around and ask not merely, “How can I solve this problem?” but, “Now that I have come to a result, what problem have I solved?” This use of reverse questions is of tremendous value precisely at the deepest parts of science.