Ernest Page, cardiac muscle biologist, 1927-2012

Ernest Page, professor emeritus in Medicine and Neurobiology, Pharmacology and Physiology, died from complications of long-term neuromuscular disease on July 21 at his home in Jerusalem. He was 85.

Page, a member of the Committee on Cell Physiology at the University of Chicago Medicine [1], was a pioneer in using the electron microscope to study biological processes and in developing rigorous mathematical techniques to analyze highly magnified images to understand the biology of heart-muscle cells and the diseases that impair heart function.

He was especially interested in the changes that occurred at the subcellular level. His early work focused on ventricular hypertrophy, a precursor to heart failure, and on how various drugs could alter the ability of cardiac muscle to contract. Later in his career, he focused on cardiac ion channels and the structure and function of cardiac gap junctions — clusters of channels that allow current-carrying ions to pass between cells, allowing electrical propagation of cardiac contraction.

“He pioneered microscopic and biochemical studies on gap junctions that form the basis of some of my current research and that of many cardiovascular scientists,” said cancer specialist Eric Beyer, professor of pediatrics at the University of Chicago Medicine. “The field didn’t care much about these cell-to-cell connections in the heart at the time; they were seen as passive. But he persisted, purified cardiac gap junctions and provided data that helped convince others that they were fundamental for understanding electrical conductance within the heart and abnormalities that cause arrhythmias.”

Page also did fundamental studies of atrial natriuretic peptide, a hormone secreted by muscle cells in the upper heart chambers in response to high blood pressure. This peptide can lower blood pressure by reducing the amounts of water, sodium and lipids in the blood. Page and colleagues showed that atrial natriuretic peptide was stored in small flask-shaped pockets in the atrial cell membranes, called caveolae, and that it was released in response to stretching of the inner walls of the atria.

“Ernest Page was a key figure in the effort, soon after World War II, to apply emerging scientific tools such as electron microscopy to biological problems at the sub-cellular level,” said Harry Fozzard, professor emeritus of medicine at the University of Chicago Medicine. “He was among the first to apply electron microscopy to the study of cardiac tissue. His work directly affected how we understand and treat certain forms of heart disease.”

One of Page’s best-known early mouse studies from the early 1970s showed how specific structures within heart muscle cells adapted to physical stress. When the aorta was partially constricted, cardiac muscle cells began to enlarge in as little as 10 days. Within each cell, he found myofibrils, the structures responsible for energy consumption, increased. At the same time, mitochondria, the structures that produce the fuel used by myofibrils to contract, decreased. This process, he wrote at the time, “may well be implicated in the ultimate development of heart failure.”

“Ernest Page was an internationally renowned physiologist and electron-microscopist,” said Rory Childers, professor of medicine at UChicago. “He was the first of those recruited by Hans Hecht, chief of cardiology in the 1960s, to build a team of scientists who would work closely with the clinicians to learn more about cardiac diseases and to use that knowledge to develop more effective therapies.”

A popular teacher and respected researcher

Despite his accomplishments, Page’s wife said he was a modest person who loved culture.

“He liked to stay out of the limelight,” Eva Page said. “But he was also a Renaissance man, a popular teacher as well as a respected researcher. He loved classical music. He read extensively, wrote poetry and completed three novels, none of them published. When he retired after 34 years at the University, he told everyone he had had a good time because he spent those years doing all the things he loved.”

Ernest Page was born May 30, 1927 in Cologne, Germany. Because his father was “a prominent lawyer, a Jew and a Social Democrat,” said Page’s son, David, the family “needed to flee Germany” soon after the Nazis came to power. They went to Paris in 1935, and then moved to San Francisco about a year later.

In 1945, when he turned 18, Page was drafted into the U.S. Army. After World War II, he earned his bachelor’s degree from the University of California at Berkeley in 1949, followed by his medical degree from the University of California at San Francisco in 1952. He did his residency training at the Harvard-affiliated Peter Bent Brigham Hospital in Boston, with additional fellowships in heart research at the University of Alabama, enzyme chemistry at the University of Wisconsin and biophysics at Harvard Medical School.

After completing his clinical training in 1958, Page was awarded a biophysics research fellowship at Harvard. A year later he was appointed an American Heart Association Established Investigator at that university, from 1959 to 1964. At Harvard, he became an instructor of biophysics in 1961 and an associate in biophysics in 1963.

Page came to UChicago in 1965 as an associate professor. He quickly built a large cardiac muscle biology research program. He was promoted to professor in 1969.

‘I consider myself to be very lucky’

Page also made a different sort of discovery in his Chicago laboratory: a technician named Eva Veronica Gross. She was a Romanian Jewish physician who had, in her words, “run away” to the West through Yugoslavia in 1965, during the Cold War, going first to Austria and then to Chicago. She began working in Page’s laboratory in 1966. They were married in 1967 and published one paper together, “Distribution of Ions and Water between Tissue Compartments in the Perfused Left Ventricle of the Rat Heart” in 1968. She completed her residency at what was then called the University of Chicago Hospitals and became a practicing dermatologist.

On vacations, the two enjoyed combining extended nature hikes with “long, lovely talks,” she said.

“In summers, we used to hike in the Rockies in Idaho and Colorado, which we both loved, going to relatively high altitudes where there were not many people, just the glorious nature and animals.”

“He was a wonderful father, spending lots of valuable time with our son, and an exceptional husband,” she added. “I consider myself to be very lucky.”

“Although he was an outstanding scientist, he always gave me the feeling that he and my mother were the center and most important part of his world,” said his son David. “I remember him daily with his arm draped around me while he read to me before I went to bed. When I was impudent or impolite to him, he never reacted with anger. He only reprimanded me when I was unkind or insensitive to others.”

A prolific researcher, Page published more than 100 peer-reviewed articles and another 100 research abstracts. He played a leadership role in many of the local and national cardiology associations, serving as a member of the American Heart Association research committee and as chairman of the Chicago Heart Association research committee. From 1981 to 1986 he was editor of the American Journal of Physiology and from 1987 to 1991 he was associate editor for Circulation Research. He and two colleagues edited The Handbook of Physiology: The Heart for Oxford Press, published in 2001.

After teaching physiology to medical students for 25 years, Page retired in 1998. He and his wife moved to Israel to be closer to their son. In addition to his wife, Page is survived by their son David and his wife Menucha, and four grandchildren: Daniela, Ben-Tzion, Betzalel and Elazar.

A funeral service was held in Jerusalem.