By Eugene Dong, M.D., J.D. and as told to him by Norman E. Shumway, M.D., Ph.D. and Richard R. Lower, M.D.

Dr. Dong's Address:
Dept. of Cardiothoracic Surgery
Stanford University School of Medicine
300 Pasteur Drive
Stanford, CA 94305

© 1995 Eugene Dong, MD, JD; last revised November 3, 1995;
Revised and updated with permission from History of Transplantation: Thirty-Five Recollections, Paul I. Terasaki, Editor © 1991 The Regents of the University of California

Part One: The Paths Less Traveled

Bellevue, NYC On a bright winter day in 1959, Eugene Dong, M.D. traveled to Stanford University at Palo Alto, looking for a training position in surgery. He was in the midst of a medical internship in the Columbia University division at Bellevue Hospital in New York City. The chairman of the Columbia Medical Division was Dickinson W. Richards, MD, who with Andre Cournand, had been awarded the 1958 Nobel Prize in Medicine and Physiology for their work leading to an fuller understanding the physiology of the human heart using cardiac catheterization techniques. Since Dong was interested in the newly developing area of heart surgery, he did not want to pass up a chance to learn from Dr. Richards, figuring that there was plenty of time later to pick up his surgical experience. Upon application to both his alma mater, the University of California at San Francisco, and the Columbia University surgical service at Bellevue, he received the news that they wanted him to take an additional year of training at the intern level in surgery before considering him for a surgical residency. So Dong was trying his luck at a new school and hospital.

Stanford University had decided to move its medical school, Stanford-Lane, San Francisco to the site of its main campus in Palo Alto, California. Stanford - Lane had been a respected, clinically oriented medical school. The move signaled primarily closer ties to the growing research faculty in the other disciplines. By 1959, few established surgeons had transferred to the suburban site. The dean of the new Stanford school, Robert Alway, M.D., had told Dong and other inductees at the 1959 Alpha Omega Alpha honor medical society induction dinner to consider Stanford's new direction in medical research at a new facility in Palo Alto.

The incoming chairman of surgery was to be J. Garrott Allen, M.D., an academic from the University of Chicago whose credentials included editing a textbook of surgery and studies on plasma and hepatitis. Allen had not yet arrived on campus. Of particular relevance to the advancement of cardiac surgery science was the fact that Frank Gerbode, M.D., a San Francisco pioneer in heart surgery, elected to stay in San Francisco.

R.B. Cohn On the particular day of Dong's visit, Roy B. Cohn, M.D. was acting department chairman. Cohn was one of the few established Stanford surgeons who made the move from San Francisco to Palo Alto. Cohn was later to perform the first kidney transplants on the West Coast between identical twins and become the mentor for Samuel Kountz, M.D. Initially Cohn indicated that there were no positions available for Dong. After a bit of conversation, Cohn learned that Cohn and Dong's uncle were poker playing students together at the old Stanford Medical School. Of such trivialities arose Cohn's suggestion to Dong that maybe a young cardiac surgeon named Norman Shumway might be interested in having a research fellow for a while.

Norman Shumway, M.D., Ph.D. was not a man to stand on the formalities either in training or of position. Shumway appeared in an office which was no larger than five feet by 10 with a single window in the far side opening on to the center well of the surgical wing of the medical school. The office was shared with another, and the two desks side by side were standard chrome trimmed tan metal desks.

After the briefest of interviews with Dong, Shumway indicated he would support Dong's application for a NIH postdoctoral fellowship. In the meantime, Shumway asked Dong if he would like to see an animal which had just survived a heart transplant operation.

The medical school building was attached to the Palo Alto-Stanford University Hospital. This hospital was as much an experiment in marrying a university medical staff with a community physician staff as was the medical school's marriage with the scientific university community. Although the hospital was subsequently purchased by Stanford and became the Stanford University Hospital, its schizophrenic birth has lingering effects.

The offices in the School of Medicine for the Department of Surgery were arranged such that they were directly across a six foot hallway from the laboratories. In Shumway's case, his laboratory was just a few doors down the hall. The laboratory was 30 by 30 feet in size. There were freshly constructed operating tables, surgical lights, an electrocardiographic machine, and a bulky heart lung machine using the latest technology: a Kay-Cross rotating disk oxygenator. And there was indeed a frisky dog with a recent surgical scar. Also present was the surgical resident, Richard Lower, M.D., who had operated on this the first animal to receive a heart from another animal in the "orthotopic" position and live. It is fair to say that among the three present that day, Shumway, Lower, and Dong, none realized the long-lasting relationship they all would have with the field of heart transplantation and with each other.

Richard R. Lower, M.D. arrived at Stanford because Lower, like Dong, had strayed off the beaten path for surgical training. Lower was raised in Michigan and went to medical school at Cornell. An interest in the outdoors caused him to choose the University of Washington in the northwest for his surgical residency in 1956. However, during his internship, Lower broached the subject of a shorter training period with the chairman, Dwight Harkins, M.D., because of Lower's initial interest in becoming a general practitioner. It was not to be. Harkins' inflexibility lead Lower to Stanford Lane Hospital in San Francisco. The surgeon in charge of residency training there, Victor Richards, M.D., indicated that he could care less how long it took Lower to achieve the training he wanted.

At that time, Stanford required their surgical residents to spend some time in research. The physical facilities of the Stanford surgical laboratories were relics of a past era even for the 1950s. A single large laboratory was used both for research and for a dog surgery course for fourth-year medical students. The wash basins were made of cement. The plumbing was exposed. There were smaller rooms where experiments were carried out in which, on rainy days, the silence of the dark and gloomy interiors was interrupted by the sound of leaking rainwater being caught in buckets.

Lower circulated among the several surgeons assisting all of them with their research projects and there met Shumway, who turned out to be a kindred spirit.

Norman E. Shumway was born in Kalamazoo, Michigan in 1923 and raised in Jackson, Michigan. His career as an attorney was cut short after just one year of prelaw studies at the University of Michigan by army service in World War 11. Recognizing that the infantry was not particularly attractive with a shooting war going on, he took the medical training opportunity presented by the Army with little vacillation. His premedical schooling was in Texas and his medical school training was at Vanderbilt University in Tennessee from which he graduated in 1949. He began his residency at the University of Minnesota graduate program in surgery.

However, after two years, Shumway was required to return to the service during the Korean conflict due to the schooling he had accepted from the government. After another couple of years, he was back at the University of Minnesota.

Owen Wangensteen, M.D. was Minnesota's famed chairman of surgery. Although Wangensteen was a general surgeon, Minnesota had developed into the central hub for fledgling field of open-heart surgery. C. Walton Lilleihei, M.D. lead the clinical effort using cross-circulation and mechanical heart-lung support and F. John Lewis, M.D. lead the effort in the use of total-body hypothermia.

Lewis Shumway1959

Wangensteen's surgical trainees formally matriculated in a doctoral program. Shumway's mentor was Lewis, and therefore Shumway's doctoral research was on the effects of hypothermia on the heart. Specifically, Shumway studied the ventricular fibrillation threshold showing that as the temperature fell, less current was needed to cause the heart to fibrillate.

However, after five years of training, Shumway felt the urge to move on without taking the rotation through Dr. Wangensteen's service, which in practical effect meant not taking the traditional chief residency.

Eschewing the academic life temporarily, Shumway initially began a private clinical practice in partnership with an older surgeon in Santa Barbara, California in 1957. By all accounts, it was not a match made in heaven, and Shumway moved again to Northern California.

Shumway's academic choices were between the University of California and Stanford-Lane in San Francisco. But Shumway recognized that UCSF was not available to him when during his interview with the department chief, Dr. Leon Goldman, Dr. Goldman fell asleep. Shumway quietly left to try his luck with Stanford.

The prospects for a young cardiac surgeon breaking in at Stanford-Lane were only minimally brighter than at UCSF, Shumway was offered running the kidney dialysis machine and all the private practice he could hustle. In real terms, the latter meant taking calls for surgeons on vacation. There was little doubt that Dr. Frank Gerbode, Stanford's established heart surgeon, was not offering Shumway any openings at Stanford in heart surgery.

The opportunity for Shumway arose from an unlikely source - Dr. Ann Purdy. Purdy was one of Stanford's pediatric cardiologists and the wife of Dr. Emile Holman, the long-time chief of surgery at Stanford. Purdy was not satisfied in her professional relationships with Gerbode and Dr. Saul Robinson, another pediatric cardiologist, and moved her base of operations to the then Children's Hospital in San Francisco.

Roy Cohn, who had been working with Purdy on non-cardiac congenital defects in children, suggested that he might be the appropriate surgeon to team with Shumway to perform heart surgery at Children's Hospital. To that end, Cohn provided funds to purchase the equipment necessary, got the referrals from Purdy, and prepared a team to perform the surgery. When the program actually began, the line-up shifted when Cohn, perhaps busy with his clinical work, absented himself from the laboratory preparation stage. Shumway who, nominally, was to operate the heart-lung machine started running the operative team.

Shumway teamed with Raymond Stofer, D.V.M. to work out the heart-lung machine and perfusion issues. Stofer, a master sergeant type in personality and appearance, was a veterinarian recruited by Stanford to oversee the operations of the surgical laboratory. Under his bluff exterior, Stofer was a master metal worker and in his private time a fine photographer. Although he had his own research projects, they were set aside when called upon to develop and operate the perfusion system. Under Shumway's direction, Stofer worked out an extraordinarily unadorned and spartan system with a minimum of gauges and monitors to watch, clean, or repair. The perfusion system was in marked contrast to the complex oxygenating system Gerbode's perfusionists and anesthesiologists had constructed and had become use to. This simplicity was to be a trademark of Shumway's conceptual approach to surgical advances.

Lower was by then collaborating with Shumway, and when the time came for the first clinical cases, the group packed the equipment in a moving van and moved lock, stock, and barrel from the Stanford-Lane laboratories to the Children's Hospital operating room. Shumway's and Cohn's first case was an atrial septal defect in a young woman which was corrected under total-body hypothermia. After the surgery, the operating equipment was all packed up and moved back to Stanford-Lane. There were fourteen more cases done at Children's Hospital before the school and Shumway moved to Palo Alto.

Part Two: Keeping It Cool

The key cardiac surgical question of the day was how to protect the heart during heart surgery. While some procedures could be carried out with the heart perfused and beating, greater accuracy in intraoperative diagnosis and repair could be gained with the heart "arrested" and the field relatively dry. Other procedures necessitated opening the aorta and thus the coronary arteries would not be perfused naturally. This was the most demanding situation. Two methods were then current: 1) use catheters and perfuse the coronary arteries and 2) use potassium arrest. Neither technique was particularly satisfactory. The first method cluttered the field with catheters and was fraught with mechanical perfusion problems. The second method gained no time for the surgeon and eventually was shown to be contraindicated.

Shumway and Lower tackled this problem in the laboratory, exploring an idea Shumway derived from his hypothermia experience. It was called "topical hypothermia." The experimental animal's body temperature was reduced using the perfusion equipment to about 32 degrees centigrade, while catheters were sutured around the edge of the opened pericardium which in turn had been sutured to the edges of the sternal wound to form a cradle. Ice cold saline then continuously flowed into the pericardial cradle, circulated around, and was then continuously sucked out. The technique limited further cooling only to the heart. The aorta was then cross-clamped so that no blood was flowing through the coronary arteries. After a period of time, the aorta was undamped, blood flow restored, and the heart defibrillated with an electric shock. After a period of support the animal could maintain its circulation on its own and the heart-lung machine was discontinued.

Successful experiment after experiment were accomplished. The technique was published in "Selective Hypothermia of the Heart in Anoxic Cardiac Arrest," Surgery, Gynecology, and Obstetrics 1959; 109:750 click here for Acrobat(tm) version.

Part Three: Switching Hearts

As the cardiac arrest time got longer and longer, Lower and Shumway started discussing what they could do to pass the time of the cardiac arrest. All sorts of fantasies were indulged in while waiting. They considered bench heart surgery where the cooled heart was taken out and operated upon on a figurative back bench, replacing parts and suturing defects under ideal operating conditions.

To this end, Lower began experimenting with autotransplantation, wherein the heart was excised and sutured back in. Lower used the same technique in excising the heart for the operation as he had for excising the heart during the postmortem examinations. He cut through the base of the atria and then the pulmonary artery and aorta separately. The heart was excised and placed in an iced saline bath and then sutured in again. However, Lower had no successful autotransplant operation despite many attempts because of the fragile nature of the experimental animal's aorta. There was insufficient tissue to manipulate the heart autotransplant in the canine model.

Lower was then moved to attempt heart transplantation. He postulated that the hearts of both the donor and the recipient could be excised such that there would be surgically adequate margins to suture the heart back together with less technical wizardry demanded. That proved to be true. So it was that Shumway's hypothermia experiments led to Lower's thoughts about how to pass the time during the experiment to the first successful heart transplant operation in December 1959.

Allen, the department chairman, was concerned about the publicity and the fact that the animal's wound had become infected. However, Lower and Shumway wisely permitted the animal to survive the postoperative period and in seven days, the animal expired. The histological sections showed the classic pattern of cellular rejection with periarterial lymphocytic infiltration.

There had been brief but extensive media coverage of the operation after Cohn mentioned the accomplishment on a San Francisco television station reviewing the year's medical news. In the print media, Lower characterized the transplantation as a 'technical stunt,' recognizing the significant immunological barriers still to be overcome. The media exposure brought unwelcome threats to Lower from the fringes of society. He would later be brought to trial by the State of Virginia for a donor's death which was successfully defended against. But, to paraphrase George Bernard Shaw, today's heresies are tomorrow's truths.

Lower, Stofer, and Shumway successfully carried out several more transplants during the spring and summer of 1960 with survival as long as three weeks. In October 1960, Lower presented his results at the Surgical Forum of the annual meeting of the American College of Surgeons: "Studies on Orthotopic Homotransplantation of the Canine Heart," Surgical Forum (1960; 11:18) Click Here for Acrobat (tm) version. There were very few listeners to Lower in the audience that day. Indeed, Watts Webb, M.D., the then leading researcher on heart transplants, gave a summary talk on transplant methods and simply said to the audience that he had heard that someone had presented a paper on a successful heart transplant at the meeting.

Part Four: Will It Pump?

Part Five: How Well?

Part Six: Suppressing Rejection In The Switched Hearts

Part Seven: Real Patients