Bert Lester Vallee, the Paul Cabot professor of biochemical sciences emeritus at Harvard Medical School, passed away in his sleep on May 7, a few weeks short of his 91st birthday. He was especially well known for his identification of zinc in various metalloproteins and enzymes, and was considered by many to be the “father of metallobiochemistry.”
Bert Lester Vallee, the Paul Cabot professor of biochemical sciences emeritus at Harvard Medical School, passed away in his sleep on May 7, a few weeks short of his 91st birthday. A brilliant biochemist, Bert left a legacy of many significant discoveries and a large cadre of scientific collaborators. He will be remembered as a passionate scientist, dedicated to finding the answers to important questions. A remarkably generous and kind colleague, Bert could be a formidable opponent when discussing science. He had a wonderful sense of humor and would often start out his scientific talks with a joke. In private, he frequently exchanged jokes with friends— always looking for new material. He enjoyed good food and wine (particularly Alsatian)— a visit with Bert was a guarantee to gourmet dining.
Bert was born in Germany on June 1, 1919 and grew up in Luxembourg. He received his Bachelor of Science degree from the University of Bern in Switzerland. He came to the United States in 1938 as the first (and only) fellow of the International Student Service of the League of United Nations. He was fortunate to be taken under the wing of Richard Courant, founder of the New York University Courant Institute of Mathematical Sciences, and ultimately received his medical degree from the New York University College of Medicine in 1943. Although he was an able physician who actively helped his friends with their medical problems throughout his life, his true calling was biomedical research. During World War II, he was assigned to the joint Harvard Medical School-Massachusetts Institute of Technology blood-preservation project directed by the protein chemists Edwin Cohn and John Edsall. This experience shaped his future career in biochemistry and biophysics.
At MIT, Bert became interested in the metabolism of iron and other metals such as zinc and copper. He quickly recognized the potential of spectroscopy, particularly emission and arc spectroscopy, for the detection of metals in biological systems. At that time, assessing the role of metals in biological systems was a quagmire for two reasons: inadequate purity of biological materials and the lack of sensitive methods to analyze for the metals. He was awarded a National Research Council Fellowship in 1948 to pursue both of these challenges in the world-famous spectroscopy laboratory affiliated with the physics, chemistry and biology departments of MIT. In 1954, he established the Biophysics Research Laboratory at Harvard Medical School and Peter Bent Brigham Hospital. This laboratory became the locus of Bert’s scientific prowess. At Harvard, Bert was named assistant professor of medicine in 1956; he rose swiftly through the ranks to become the Paul C. Cabot professor of biological chemistry in 1965.
Bert believed that scientific discovery relied heavily on technical advances. Throughout his career, he either developed his own technologies or was an early adapter of techniques developed by others. Consistent with this philosophy, he proceeded to build a flame spectrometer designed to detect and quantify sodium, potassium, magnesium and calcium in biological samples. This early instrument was prototypical of later instruments that are used for monitoring these elements in clinical samples and the detection of diseases associated with their dysregulation. Very quickly, Bert’s laboratory became the world center for the analysis of trace metals in biological samples. These analyses depended on two factors: the ability to obtain an uncontaminated biological sample and the unique equipment available in his laboratory. Trace metals were found in unexpected places, and, in some cases, the putative role of metals in biological mechanisms was ruled out after careful analysis.
Visiting Bert’s laboratory in the Peter Bent Brigham Hospital was an adventure. To gain entry, it was necessary to wander through the basement of the hospital, among the steam pipes. Upon opening the door to his lab, a wondrous transformation occurred— a modern laboratory equipped with every conceivable instrument used in biophysics emerged, with people scurrying about, hard at work.
Bert Vallee is especially well known for his identification of zinc in various metalloproteins and enzymes. Because of his work on the role of metals in biological systems, many consider him to be the “father of metallobiochemistry.” Among the many zinc proteins studied in his laboratory, carboxypeptidase merits special mention. His laboratory carried out very careful and extensive mechanistic studies of this enzyme that not only elucidated its reaction mechanism but also provided structural information. Again, multiple techniques were used in this work, including spectroscopy, stopped-flow kinetics and chemical modification. In particular, the roles of specific amino acid residues at the active site were assessed. When the X-ray structure ultimately emerged, Bert’s results proved to be remarkably accurate.
Alcohol dehydrogenase was another zinc-containing enzyme extensively studied by the Vallee laboratory. Bert was especially interested in the role of this enzyme in alcohol metabolism and the general problem of alcohol addiction. He showed that genetics are important for the disease of alcoholism, and his work has led to clinical trials of drugs for the treatment of the disease. In 1957, he discovered the unique protein metallothionein, a low-molecular weight cysteine-rich protein. The protein binds zinc atoms very tightly and has been implicated in the homeostasis of zinc metabolism. It also binds many other metals tightly, and recent results suggest that the redox properties of copper, when bound to metallothionein, may be of significance in neurodegenerative diseases.
As a consultant to Monsanto, he initiated one of the early collaborations between a university and industry. The research was directed toward isolating chemicals that led to new blood vessels in tumors. His laboratory characterized one of these chemicals, angiogenin, which proved to be a ribonuclease analog.
Bert’s bibliography includes more than 650 publications, comprising research articles, books and reviews. He was recognized widely for his scientific accomplishments and was elected to the National Academy of Sciences and the American Academy of Arts and Sciences. Among his many awards were the Linderstrom-Lang Medal, the Willard Gibbs Medal from the American Chemical Society and the William C. Rose Award from the American Society for Biochemistry and Molecular Biology. He received honorary degrees and professorships throughout the world and served on the editorial boards of multiple journals.
Bert wanted to leave a living memorial for science, and, in 1995, he and his wife Natalie, known as “Kuggie” to her friends, established the Vallee Foundation to foster originality, creativity and leadership in science. A primary activity of the foundation is to fund honorary Vallee professorships for well-known scientists. The purpose of these short-term (typically four weeks) visiting professorships is to permit accomplished scientists to explore new areas and to establish close interactions with other successful senior investigators that might lead to new knowledge. Bert approached this foundation with his usual passion and zeal, and many researchers and laboratories already have benefited from his endeavors. At the time of his death, he was organizing a meeting of the Vallee Foundation for the summer of 2010. Although Bert was adamant about not wanting a memorial service, this meeting will be held as a living tribute to a remarkable man. He will be sorely missed by his friends and colleagues, but his scientific accomplishments and the Vallee Foundation remain as lasting remembrances.
Gordon G. Hammes (firstname.lastname@example.org) is the university distinguished service professor of biochemistry emeritus at Duke University, and S. James Adelstein (email@example.com) is the Paul C. Cabot distinguished professor of medical biophysics at Harvard Medical School.
Please feel free to add your reflections on Bert Vallee in the comment section below.