1. Kim, Meeri PHD

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Lee W. Wattenberg, MD, a pioneer in the field of cancer prevention and widely known as the "father of chemoprevention," died Dec. 9 in Minneapolis. He was 92.

LEE W. WATTENBERG, M... - Click to enlarge in new windowLEE W. WATTENBERG, MD. LEE W. WATTENBERG, MD (1921-2014)

Wattenberg was Professor of Medicine at the Masonic Cancer Center of the University of Minnesota, the school where he also received his medical degree. He joined the faculty after graduation and served there for more than 60 years, most recently in the Department of Laboratory Medicine and Pathology. During his career, he also held leadership positions at the American Association for Cancer Research and received the AACR Award for Lifetime Achievement in Cancer Prevention Research in 2010.


His groundbreaking work in compounds found to prevent the development of cancer in animals saw the launch of a whole new scientific field.


"He was an example of a scientist with a concept that absolutely drove his whole life," said Stephen S. Hecht, PhD, the Wallin Professor of Cancer Prevention, American Cancer Society Professor, and American Chemical Society Fellow at Masonic Cancer Center. "He kept following this particular concept because he believed in it so thoroughly-and because of his strong belief and strong work, many other people followed."


Wattenberg's 1966 paper in the journal Cancer Research (1966;26:1520-1526) summarized a group of animal experiments that showed inhibition of carcinogenesis through the administration of certain chemical compounds.


The mechanisms behind some of these compounds were not well understood, but others appeared to increase the activity of carcinogen-detoxifying systems or inhibit the initiation of carcinogenesis. This discovery triggered the idea of preventing cancer by taking the compounds as drugs or eating foods that contained them naturally. Wattenberg coined the term "chemoprophylaxis" to refer to the prevention of disease by chemical agents.


In an interview, Hecht, his sometime tennis partner and research collaborator for over 20 years, recalled how many scientists built upon Wattenberg's thorough experimental work to create chemopreventative medications. For instance, Wattenberg's studies on myo-inositol have directly contributed to its development as a drug for preventing lung cancer, which is now in Phase II clinical trials at the Mayo Clinic.


"Lee was one of the first to demonstrate that myo-inositol, which is a common dietary constituent, can prevent cancer in animal models," said Hecht. The compound is naturally found in fruits, beans, whole grains, and nuts.


Other research showed how diet could influence the metabolism of benzopyrene, a classic carcinogen. A common constituent of broccoli, cabbage, and other vegetables called indole-3-carbinol appeared to have a protective effect against benzopyrene and somehow decreased its toxicity in animals.


Ingenious Studies

"Lee was the first to really establish that naturally occurring compounds found in vegetables can prevent cancer," Hecht said. "He did this through a series of ingenious studies where he looked at different diets that were fed to animals treated with carcinogens, and then went on to examine some of the individual constituents that were in the vegetables and showed that these chemicals can prevent cancer."


Since the original paper on indole-3-carbinol, hundreds of studies were done on the compound to tease out its true chemopreventative ability. Although the story did turn out to be much more complicated, with some studies finding that indole-3-carbinol could in certain cases be a tumor promoter, the experiments nevertheless spurred the growth of a field and a different way of looking at cancer and the effects of diet.


"The extensive studies that Lee did on various agents that blocked metabolic activation of carcinogens were certainly some of the most important experiments done in this entire field," said Michael B. Sporn, MD, Professor of Pharmacology and Medicine at Dartmouth Medical School, another pioneer in the field of cancer prevention, who first met Wattenberg over 30 years ago.


Sporn remembers his colleague as a "meat-and-potatoes type of person-not very flashy, but sound and methodical." He recalls spending time with Wattenberg at various conferences, and sharing with him a belief that more effort should be put on preventing cancer rather than treating end-stage disease.


"Almost all of the effort now is still going into treating end-stage disease, besides smoking cessation and eating better," he said. "There's no serious effort in preventing cancer, especially using drugs."


'True Passion for His Work'

But the general disinterest in chemoprevention failed to deter Wattenberg's drive. Hecht noted that like most successful scientists, Wattenberg had a true passion for his work, waking up in the morning already thinking about his projects and what steps to take next.


Wattenberg was President of AACR from 1992 to 1993 and was also on the association's board of directors. An active AACR member since 1961, he was elected to the first class of Fellows of the AACR Academy, in 2013.


He was born in New York City and received his Bachelors of Science degree from City College of New York in 1941. Throughout his esteemed career, he published more than 150 scientific publications and influenced countless other researchers through his work.


"He was just a giant in the field-when you think of Lee Wattenberg, you think of chemoprevention, but chemoprevention is just one part of cancer prevention, and that's not always clear to people," Hecht said. "The work he did in chemoprevention with animal model work made it clear that cancer prevention is possible."


Remembered as an extremely kind, gentle, and thoughtful person, Wattenberg is survived by his wife of 70 years, Esther, their four children (Elizabeth, Anne, Mark, and Binks), eight grandchildren, and a great-granddaughter. He was preceded in death by his son, Richard, and daughter, Lynn.


"Lee was interested in politics, he was a good tennis player until his knees gave out, and he was a family man-but it was the science that really drove him," Hecht said. "Everything else just fell into place."