Nuclear medicine pioneer Paul Harper, 1915-2005

August 3, 2005

A pioneer in the diagnostic and therapeutic uses of radiation and the development and testing of radiotracers in the early days of nuclear medicine, Paul V. Harper, MD, professor emeritus in the departments of surgery and radiology at the University of Chicago, died at the Palliative Care Center and Hospice of the North Shore, in Evanston, Illinois, on July 15, 2005, from pneumonia after suffering complications of diabetes. He was 89.

Harper was the key member of a University of Chicago research team--including Katherine Lathrop, Don Charleston, and Robert Beck--that was one of the first to investigate several of the tools of modern nuclear medicine. They are perhaps best known for introducing technetium-99m into clinical practice in the early 1960s as a radiotracer agent. This substance is now used about 35,000 times a day in the United States and 20 million times a year worldwide in nuclear medicine scans designed to identify tumors or abnormal physiologic processes.

Harper and Lathrop also developed the commercial method for producing iodine-125, another commonly used diagnostic radionuclide. Harper and colleagues were among the first to investigate the medical applications of dozens of radioactive isotopes, including the use of thallium to assess the heart muscle--another test in common use today.

They were also leaders in the use of various types of radioactive implants to deliver a therapeutic dose to tumors. This form of treatment has become routine for prostate cancer, but Harper found ways to apply it to many other sites throughout the body--including the pancreas and the brain.

"Paul Harper was insatiably curious and intellectually fearless," recalled Robert Beck, professor emeritus of radiology at the University of Chicago. "Although he trained as a surgeon, he was willing and able to learn whatever he needed--whether it was math, physics, chemistry, nuclear physics, dosimetry--anything that would help him attack the problem. And almost daily he thought up new problems, new things that needed to be done. For sheer imagination and creativity, there aren't many like him."

"Paul bridged the gap between surgery and radiology," said neurosurgeon John Mullan, MD, professor emeritus of surgery at the University of Chicago. "He was extremely gifted--a great scientist. He was also a wonderful teacher who stimulated everyone around him and who bestowed all the credit on them. He was the quintessence of what an academic at a major medical center ought to be. And there are damn few of them."

Born July 27, 1915, in Chicago, Paul Vincent Harper was the grandson of William Rainey Harper, the founder and first president of the University of Chicago. To gain some distance from that legacy, "I've always sort of retreated from that," he told one interviewer. He went to college at Harvard, where he majored in biochemical sciences. He did research for his senior thesis with George Wald, PhD, who would win the Nobel Prize in 1967, and graduated with honors in 1939.

Harper completed Harvard Medical School in 1941 and began a surgical residency at the University of Chicago. He joined the Army in 1942. He served for three years during World War II, spending much of 1944 and 1945 in France, then returned to Chicago in November 1945. He completed his residency in 1951 while also serving from 1949 to 1953 as an instructor. During his training he worked closely with Dwight Clark, MD, a surgeon who studied radioactive iodine therapy for thyroid disease.

Harper was promoted to assistant professor of surgery in 1953, associate professor in 1955, and professor in 1960. From 1963 to 1967 he served as assistant director of the Argonne Cancer Research Hospital (ACRH), an Atomic Energy Commission facility that opened in 1953 on the University of Chicago campus. Its mission was to study the use of radioactive materials and radiation beams in the diagnosis and treatment of cancer. In 1972 he became a professor in the department of radiology as well. He became a professor emeritus in 1986, but remained active in research until about one year ago.

A prolific researcher who shunned administrative tasks, Harper published nearly 200 book chapters and research articles and more than 200 research abstracts. He won several honors, including the Paul Aebersold Award, from the Society of Nuclear Medicine. He was a founder of the American Board of Nuclear Medicine.

His remarkable productivity can be traced, in part, to his tight-knit research group; an institutional culture that nurtured creativity, innovation, and gumption; ample and steady research funding from the Atomic Energy Commission; and the relaxed regulatory climate of the time.

"It would be impossible today to replicate Paul's research style," Beck noted. "He was careful and conscientious and very protective of his patients, but he generated ideas for diagnostic tests constantly and thought up novel ways to test them, which often started with trying them on ourselves."

"You don't give anything to a patient," Harper explained during a 1995 interview, "that you haven't tried on yourself." After a lifetime of working with and self-administering many forms of radiation, Harper was proud to note that the only harm it ever did him was some damage to one thumbnail.

In the 1950s, Harper and colleagues concentrated on therapeutic uses of radiation. They invented techniques to deliver a controlled dose directly to tumors, such as coiling a thin tube around a cancerous pancreas and then filling the tube with radioactive iodine. They inserted yttrium-90 pellets or strontium-90 needles into pituitary glands for Parkinson's disease. They implanted radioactive seeds around a malignant prostate gland, a technique that is now common.

Around 1960, Harper's team began to shift their focus toward the diagnostic applications of radiation. They played a major role in the birth of nuclear medicine by developing the first clinical application of technetium 99m, the field's primary diagnostic agent. In 1960, Harper met Powell Richards--a chemist at Brookhaven National Laboratory who had developed a method for producing technetium 99m--on a flight to a meeting in Rome. They discussed possible uses of technetium. At the same time, Robert Beck--from Harper's team--presented a theoretical study suggesting that gamma rays, such as those produced by technetium 99m, would be ideal for scanning the brain.

Harper soon bought a technetium generator from Brookhaven and the ACRH team performed the first technetium brain scan in 1961, which was "not very good," recalled Beck. However, it encouraged the team to design and build their own brain scanner and they performed the first brain scan with it in 1963, which was "spectacular." They published the results in January, 1964, the first publication to mention clinical applications of technetium, and "the field took off," said Beck.

Although he was always painfully shy, Harper earned a reputation, as much among faculty as students, as an inspirational teacher. "He was a born, gifted teacher," recalled Mullan, "and his preferred podium was the coffee pot in the surgeons' locker room. For half an hour every morning you could find him there, talking about science, introducing young faculty to the rewards of research, providing ideas that launched a lot of careers. He was our intellectual guru."

Mullan was a member of the Dodecahedron, an informal select society formed by Harper of 12 scientist-surgeons who met monthly for lectures. "You had to talk for an hour about a field wider than your expertise," he said. "We all remember those as formative events in our careers."

In 1939, while at Harvard Medical School, Harper married Phyllis Sweetzer, who graduated from Wellesley. An internationally recognized expert on judo, she kindled the same passion in her husband, who became a fourth-degree black belt. People who came to parties at their house were invited to a basement carpeted with judo mats, and challenged. The Harpers never lost.

Phyllis Harper died in 1993. Paul Harper is survived by one sister, Jane Overton of Chicago, and four children: Stephanie, 64, of Glencoe, Illinois; Cynthia, 62 of Chicago; William, 61, of Hartford, Connecticut; and David, 58, of Pennington, New Jersey; plus one niece, two nephews, and two grandchildren; and Syble Paden, a close friend who helped care for Mrs. Harper when she was ill and continued to care for Dr. Harper.

A memorial service at the University is being planned for late September.