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The Edward D. Freis Papers

Biographical Information

[Edward Freis giving a presentation]. [ca. 1979].
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Edward David Freis, whose pioneering clinical studies revolutionized the treatment of high blood pressure, was born in Chicago on May 13, 1912. He was the youngest of four sons of Roy Freis, a real estate developer, and his wife Rose. Freis grew up in Chicago and graduated from Nicholas Senn High School in 1930. Prone to asthma, he chose to attend the University of Arizona, partly for the warm, dry climate. He hoped to become an actor, and took time off from college to train at the Pasadena Playhouse. (A sympathetic uncle supported this endeavor, in defiance of Roy Freis's wishes. The elder Freis vowed to disown his son, but later relented.) Freis soon decided that he was not tall enough to succeed in show business and returned to the university, where he got his BS in 1936. That same year, he married Willa Hussey, a fellow student at Arizona. They had three children, a son and two daughters.

Freis had been inspired to pursue a career in medicine after reading Paul De Kruif's popular books, Microbe Hunters and Hunger Fighters. He received his MD from the College of Physicians and Surgeons at Columbia University in 1940. Following his internship and one year of residency at Massachusetts Memorial Hospital and the Boston City Hospital, Freis joined the U.S. Army Air Forces (now the U.S. Air Force) and served as assistant chief, then chief of the laboratory service at Lincoln Air Force Base in Lincoln, Nebraska, from 1942 to 1944. From 1944 to 1945 he headed the laboratory service for the USAAF Rheumatic Fever Research Program at Gowen Field in Boise, Idaho. After the war, Freis returned to Boston for a cardiology residency at Evans Memorial Hospital, followed by a research fellowship there. Under the supervision of Robert Wilkins, he began his clinical research into hemodynamics--the mechanism of blood circulation--and the drug treatment of hypertension, an area that he would help transform during the next five decades.

High blood pressure--hypertension--itself was not considered a disease in the early twentieth century. Physicians recognized the condition but except in extreme cases did not understand it to be pathological. It seemed a normal part of aging, probably unconnected to cardiovascular or kidney disease. And until the 1940s there was no safe and reliable way to lower it in any case. In cases of malignant hypertension (diastolic pressure higher than 130) surgeons could sever nerves in the sympathetic nervous system, thus slowing the heart rate and relaxing the arteries, but this was a hazardous procedure. Freis and his colleagues began looking for drugs that might be used to lower blood pressure. A new drug, pentaquine, and an older one, veratrum viride, looked promising. The team conducted clinical trials and demonstrated that the drugs could indeed lower blood pressure in severely hypertensive patients. Unfortunately, the drugs' unpleasant side effects and the need to give them by injection made them unsuitable for routine or prolonged use.

In 1949, Freis was appointed Assistant Chief of the Medical Service at the Veterans Administration (VA) Hospital in Washington, DC, with a joint appointment as Adjunct Clinical Professor of Medicine at Georgetown University School of Medicine. He also served as director of Georgetown's Cardiovascular Research Laboratory (1949-1965) and Chief of the Hypertension Clinic there (1950-1960). In 1954 he became Chief of the VA Medical Service, and in 1959 was named Senior Medical Investigator. During this period he continued his investigations into the mechanisms and control of hypertension. New antihypertensive drugs were gradually developed, including the ganglion blockers, such as hexamethonium and reserpine, and hydralazine, a vasodilator. Of perhaps greater importance was the introduction of the first thiazide diuretic, chlorothiazide, in 1956. Diuretics--agents that increase the excretion of urine--proved very effective in reducing blood pressure in many patients, alone or in combination with other drugs, with far fewer side effects.

At about the same time, the researchers at the VA began a controlled clinical trial to evaluate this growing arsenal of antihypertensive drugs. Controlled clinical trials were something of a novelty at the time, but the VA had done a similar study to evaluate the effectiveness of drugs for treating tuberculosis several years earlier. Thus, Freis and his colleagues were able to draw on the expertise of the VA biostatisticians to design their drugs trial. The hypertension study begun in 1956 focused on comparing the effectiveness of the drugs then in use. A larger future study was also discussed, which would evaluate the effects of hypertension treatment on morbidity and mortality. Although many new drugs had been developed during the 1950s for treating hypertension, there was still no proof that they provided long-term benefits for any but the most severe forms of hypertension.

In 1962 Freis led a VA team in designing a five-year study which would determine whether treating hypertension would help prevent death and incapacity due to complications such as stroke, congestive heart failure, kidney damage, and heart attack. The study, which ran from January 1964 through December 1969, was one of the first randomized, placebo-controlled, double-blind, multi-institutional clinical trials done in the United States. A total of 523 patients at 17 VA medical centers participated in the trial. The VA study demonstrated that the incidence of major hypertensive complications in the treated groups of patients was, on average, less than half that in the control groups. Treatment dramatically reduced the number of strokes, congestive heart failure, and progressive kidney damage, although it did not prevent heart attacks and sudden cardiac death. The VA study proved that even moderately high blood pressure, if left untreated, could lead to disability and death.

The study results were published in 1970, to relatively little fanfare. They attracted more attention the following year, when Freis was honored with a Lasker Award for his leadership of the VA study. Philanthropist and health policy advocate Mary Lasker, head of the Lasker Foundation, believed that the study revealed a major public health problem that should--and could--be remedied. She asked Elliot Richardson, Secretary of Health, Education, and Welfare, to establish a hypertension education program to alert physicians and the general public about this "silent killer." The National High Blood Pressure Education Program was started in 1972 and launched a successful nationwide campaign for hypertension awareness, screening, and treatment. During the next two decades, public awareness of hypertension's role in heart disease and stroke increased three-fold, and the mortality rates from those diseases dropped dramatically.

Freis continued to direct cooperative studies on hypertension, and to advocate the treatment of the condition, becoming recognized as one of the world's foremost authorities. In 1979, with science writer Gina Kolata, he wrote The High Blood Pressure Book, a guide for patients and their families, which won the American Heart Association's Howard Blakeslee award in 1980. Freis broadened his research into various aspects of hypertension treatment, including the role of race in treatment outcomes and the use of medications for elderly patients. He conducted clinical trials on new hypertension drugs, such as the beta blockers (which slow the heart rate) and angiotensin-converting enzyme (ACE) inhibitors (which block the production of angiotensin II, a hormone that causes blood vessels to narrow) as they were developed. He also participated in many discussions about how and whether to treat mild hypertension.

By the mid-1980s there were growing concerns about the use of diuretics in hypertension treatment, specifically the danger that they might cause potassium depletion and induce dangerous cardiac arrhythmias. Some critics argued that with all the new antihypertensive drugs available there was no need to use "obsolete" drugs like diuretics in any case. Freis had long recommended diuretics--which were safe and inexpensive--as the first step in hypertension treatment, alone or in combination with other drugs. He and his colleagues conducted several surveys of the medical research literature and concluded that there was no evidence that diuretics posed a serious hazard. Even so, diuretic use declined during the next fifteen years. Later Freis's position was vindicated by the ALLHAT (Antihypertensive and Lipid Lowering Treatment to prevent Heart Attack Trial) study (1994-2002), which showed that treatment with diuretics controlled blood pressure better, and was significantly better for preventing cardiovascular disease events, when compared to treatment with ACE inhibitors, calcium channel blockers, or alpha-adrenergic blockers.

Freis retired in 1987, and was named Distinguished Physician by the VA Medical Center and Professor Emeritus by Georgetown University School of Medicine. He continued to advise ongoing clinical studies, and to publish about hypertension for nearly two decades. At the time of his death on February 1, 2005, he was working on a second hypertension book for a popular audience.

Dr. Freis published over 400 articles and book chapters during his long career, and held membership in many professional societies, including the American College of Physicians, the American Heart Association, the American College of Cardiology, and the American Society of Pharmacology and Experimental Therapeutics. He received many awards besides the Lasker, including the James D. Bruce Award in preventive medicine (1977), the ASH/Abbott Special Achievement Award from the American Society of Hypertension (1990), the first Stevo Julius Award for Education in Hypertension from the International Society for Hypertension (2000) and the Meritorious Accomplishment Award from the American Heart Association (2001). He also received an honorary Doctorate of Science from Georgetown University Medical Center in 1995. In 1985 the National Conference of High Blood Pressure Councils established the Edward D. Freis Award in his honor.

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