University of California: In Memoriam, 1991

John Hundale Lawrence, Biophysics: Berkeley

Professor of Medical Physics,
Regent of the University of California

In the summer of 1935, John Lawrence took leave from his post as Instructor in Medicine at Yale University to spend a few weeks at Berkeley to undertake studies with radioactive phosphorus, one of the first artificial isotopes produced by the beams of his brother Ernest's cyclotron. He injected soluble radioactive phosphorous into a group of leukemic mice and then left to go fishing on the Trinity River. When he returned a few weeks later, the mice were much improved, no doubt due to the beta radiation they had received. The excitement of this discovery was too much for John to resist. With the encouragement of his Harvard mentor, Harvey Cushing, he left Yale to become a pioneer of nuclear medicine at Berkeley. On Christmas Eve of 1936, he administered to a 28-year-old woman suffering from leukemia, a dose of radiophosphorus. This was the first time that a radioactive isotope produced by the cyclotron had been used to treat a human patient. In the years to come, the method became a standard treatment for the blood disease known as polycythemia vera, an uncontrolled proliferation of red blood cells. One of his later patients was Cardinal Aloysius Stepinac, who was given asylum by the American Consul in Budapest from Communist persecution. Five years later, in 1951, the Cardinal was released to the Tito government under restrictions. Summoned to Zagreb, Yugoslavia, John administered radiophosphorus to the cardinal, who was suffering from polycythemia. In recognition, Lawrence received a medal from Pope Pius XII.

The cyclotron was potentially capable of producing copious neutrons, discovered a short time earlier by Chadwick. Initially, these particles were considered to be relatively harmless as compared to X-rays. For about two years, the physics staff moved freely about their

unshielded machine. The first meaningful scientific study of the biological effects of neutrons was carried out in 1935 by John and Paul Aebersold, who found that neutrons were much more harmful than X-rays. Since lead shielding had proven ineffective, a large number of water-filled cans were piled around the accelerator. These were among the first steps in the creation of a new field: health physics.

In 1937 John made another startling observation: He found that a rodent tumor, sarcoma 180, was more sensitive to neutron radiation than were normal tissues! No such difference was observed for X rays. John and Ernest Lawrence then proposed that neutrons be tested in cancer therapy. In response to their request, the Rockefeller Institute made a grant to finance the first “medical” accelerator, the 60-inch cyclotron. It was soon demonstrated that neutrons were effective in killing human tumors, but that they also produced late deleterious effects.

Lawrence's work with cancer patients attracted the interest of William Donner, a Philadelphia industrialist and philanthropist, whose son had died of cancer. Donner contributed funds for construction of the building at the Northeast corner of the Berkeley Campus that bears his name. Donner Laboratory was dedicated in 1942 to the “applications of physics, chemistry and the natural sciences to biology and medicine.”

The availability of radioisotopes presented a tremendous challenge to investigate the dynamic turnover of chemical species in living systems. Experiments by Lawrence and his associates included work with radioactive sodium, potassium, iodine, iron, strontium and other elements.

John Lawrence elected to aid the war effort by applying the new science to the important field of aviation medicine. He was assisted by Hardin Jones, a physiologist, and Cornelius Tobias, a physicist. Working with nitrogen analogs, radioactive argon, krypton and xenon, they were able to prove that “preoxygenation” was a way to overcome “bends,” a debilitating condition limiting the altitude ceiling of aviators. It was also discovered that breathing inert xenon gas produced anesthetic effects.

Initially, the Medical Physics Division of the Physics Department was the academic home of Lawrence and his associates. In 1947, an interdisciplinary faculty group was organized, doctor's degrees were offered in biophysics and medical physics, and master's degree in bioradiology. John encouraged and fostered innovation in many aspects of biophysics. The division eventually added B.A. degrees and became the Department of Biophysics. Macromolecular structure, lipoprotein dynamics, basic radiation biology and genetics, irreversible

thermodynamics and neurobiophysics were among the courses offered. In the ensuing decades, hundreds of individuals came to Berkeley to study with Lawrence and the staff, many from foreign countries.

In 1948, John became Associate Director of the Radiation Laboratory. Much of his time was occupied with planning new projects for Berkeley and the programs of the Atomic Energy Commission elsewhere. In 1955 he was one of the organizers of the “Atoms for Peace” conference at Geneva. He traveled extensively, gave many lectures, and accepted awards and honorary degrees from three universities, including his alma mater, the University of South Dakota. In 1970, he was elected to the presidency of the Society of Nuclear Medicine and received the “Nuclear Pioneer” award. John Lawrence's philosophy of leadership included creation and maintenance of an environment where leaders in medicine, science, and education could mingle with students and young investigators in the pursuit of new ideas in biological science, new technologies for medical science and methods for treatment of disease. This led to the discovery of cholesterol and lipoprotein relationships to heart disease as well as to major underpinning of nuclear medicine.

The years following the war also saw the beginnings of several important research programs. John and a group of young physicians used long-lived radioiron to label hemoglobin in red blood corpuscles and demonstrated that iron was transported to the bone marrow by a protein; they were also able to measure the life span of red blood cells. Later, with laboratory scientist Will Siri, John made expeditions to the Andes to study red cell production at high altitudes. This work led to pioneering studies of erythropoietin, the hormone that controls the production of red blood cells.

Robert Wilson, who eventually became the director of Fermilab, suggested at Berkeley in 1946 that high energy protons might be useful in cancer therapy because of the “Bragg effect,” the property of delivering a good deal of the particle energy deep in tissue. Lawrence and his group became interested in this approach and began investigating it at a time when very little was known about the biological effects of these particles. The 184-inch cyclotron was completed in 1947, and investigations began with protons, deuterons and helium ion beams.

In 1951, Hal Gray of the Hammersmith hospital in London proposed that high LET radiations were more effective on tumor cells, which were often constrained to live in an oxygen-deficient milieu. The Swedish surgeon, Herbert Olivecrona demonstrated independently that surgical removal of the pituitary gland could produce

astonishing regressions of human mammary cancer. In 1954 the first patient with advanced mammary cancer received pituitary proton radiation. Eventually several hundred patients were treated, most of them suffering from acromegaly, a debilitating tumor of the pituitary gland. Medically, John was assisted by James Born and other physicians in his group. As a physician, Lawrence was compassionate, and dedicated to his patients. It was shown that nonsurgical pituitary particle radiation could permanently interfere with the production of somatotropic hormone and produce tumor regressions lasting for many years.

The avalanche of scientific and medical investigations that followed are still in progress today. Currently the largest Berkeley accelerator, the Bevalac, is being utilized. Trials are under way for the treatment of several types of cancer with heavy ion beams. The particles are also proving effective for the treatment of life threatening arteriovenous malformations in brain. A new medical proton accelerator has been built at Loma Linda University. Several countries, including Germany and Japan are building heavy particle accelerators for biomedical research and treatment.

In 1970, when Lawrence retired as director of Donner Laboratory, he was asked by then Governor Reagan to become a Regent of the University of California. During his 13-year-tenure, he was instrumental in promoting advanced education in the medical sciences. In 1983, he received the Enrico Fermi award for his “pioneering work and continuing leadership in nuclear medicine.”

During the last few years of his life, he kept a table next to his bed, filled with scientific and medical books. When unable to sleep, he would get up to read at any time of day or night. John's interest in both cancer and atomic research never flagged. It was this indomitable spirit, and his ability to create an environment of freedom in research for scientists and students alike, that are attributes we most admired in John Lawrence. He had a great sensitivity to human suffering, and he believed that humans can solve many of their problems through scientific pursuits.

John lost his wife Amy in 1967. He is survived by their four children, Shelley de Rouvray of Paris, Mark of Los Angeles, James of Alamo and Steven of Alamo, and eight grandchildren.

Thomas Budinger Howard Mel Cornelius A. Tobias

About this text
Courtesy of University Archives, The Bancroft Library, University of California at Berkeley, Berkeley, CA 94720-6000;
Title: 1991, University of California: In Memoriam
By:  University of California (System) Academic Senate, Author
Date: 1991
Contributing Institution:  University Archives, The Bancroft Library, University of California at Berkeley, Berkeley, CA 94720-6000;
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