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Submitted: 4/18/2014 (originally submitted, 4 October 2011)
Two interview sessions: September 26 and 27, 2011
Approximate total duration:
Interviewer: Tacey A. Rosolowski, Ph.D.
About the Interview Subject:
Dr. Isaiah J. Fidler (b. Jerusalem, Israel, 1936) was recruited to MD Anderson in 1983 to establish the Metastasis Research Laboratory. He is the Director of the Metastasis Research Laboratory in the Dept of Cancer Biology. He is a Professor in the Department of Cancer Biology with a joint appointment in the Graduate School of Biomedical Sciences.
Major Topics Covered:
Personal and educational background
The “seed and soil” theory; theory of cancer as a regulated, predictable process
The practice of basic and translational research
Regarding the Transcript and Audio Files
In accordance with oral history best practices, this transcript was intentionally created to preserve the conversational language of the interview sessions. (Language has not been edited to conform to written prose).
The interview subject was given the opportunity to review the transcript. Any requested editorial changes are indicated in brackets [ ], and the audio file has not correspondingly altered.
Redactions to the transcript and audio files may have been made in response to the interview subject’s request or to eliminate personal health information in compliance with HIPAA.
The views expressed in this interview are solely the perspective of the interview subject. They are not to be interpreted as the official view of any other individual or of The University of Texas MD Anderson Cancer Center.
Table of Contents
Interview Session One: 26 September 2011
From Veterinary Medicine to Cancer Research
Chapter 01 / Professional Path
A New World of Research at University of Pennsylvania: Focusing a Research Career
Chapter 02 / The Researcher
Metastasis: A Regulated Process
Chapter 03 / The Researcher
Reflections on Research; Becoming a Citizen; Influences: Words of Wisdom
Chapter 04 / Personal Background
Interview Session Two: 27 September 2011
Recent Research: A Focus on Brain Metastasis
Chapter 05 / The Researcher
Brain Metastasis: Activating the Body’s Capacity to Heal Itself
Chapter 06 / The Researcher
Translational Research at MD Anderson
Chapter 07 / The Researcher
Session One: September 26, 2011 (listen/read)
Interview Identifier (listen/read)
Chapter 01 (Professional Path)
From Veterinary Medicine to Cancer Research (listen/read)
In this Segment, Dr. Fidler talks about his youth in Israel, the decision to study veterinary medicine that brought him to the United States in 1958, and the later events that inspired his shift from veterinary medicine to the study of cancer in humans. In 1961 he received his B.S. in Veterinary Medicine at Oklahoma State University, Stillwater, Oklahoma. Dr. Fidler was awarded his Doctorate in Veterinary Medicine from the same institution in ’63. He describes the difficulties of setting up a veterinary practice upon returning to Israel, where pet owners chose to terminate the lives of even beloved pets much more quickly than they do today. “I didn’t work so hard to become an executioner,” he recalls, explaining decisions that took him from private practice, to pharmaceutical research, and eventually back to the U.S. for a fellowship at the University of Pennsylvania Veterinary School, where his work on animals with cancer sparked his passion for problems of metastasis. After receiving a fellowship that enabled him to conduct basic research at the U. Penn. Medical School, he was advised to apply to the Department of Pathology, where many scientists were conducting research on metastasis. He received his Ph.D. in (human) Pathology from the University of Pennsylvania Medical School (Philadelphia) in ’70. There he framed the basic question that would govern his career: how cancer moves from the primary tumor via the circulatory system to create secondary tumors and ultimately the metastases that are still the primary killers of cancer patients. After receiving his Ph.D., he went to work in the Department of Pathology in the U. Pennsylvania Dental School with a Luther Terry Fellowship(late ’70).
Chapter 02 (The Researcher)
A New World of Research at University of Pennsylvania: Focusing a Research Career (listen/read)
Dr. Fidler details how he began to look more deeply into the question of cancer cell differentiation, a groundbreaking discovery that was ultimately published in Nature. (Dr. Fidler shows the interviewer a Plexiglas containing a unit he invented to facilitate injection of cells into the tail veins of up to 100 mice per hour, underscoring the resourcefulness that a researcher had to have to move ahead quickly with a study.) Through this success, he was recruited to join the National Cancer Institute at Frederick, Maryland. His wife-to-be, Margaret Kripke, known for her pioneering work in photoimmunology, was also hired in a concurrent recruitment, and he describes how Dr. Kripke challenged him with the question that inspired a new line of research: “How do you know whether the cells you are culturing from a line are a selection or an adaptation?” His discovery that the differentiation of metastasis cells is a priori “revolutionized the world,” he states, noting that “you cannot treat a heterogeneous disease with homogeneous therapy” –the origin of individualized therapy. Dr. Fidler then explains connections between Paget’s “seed and soil” theory and his next experiments with transplanting metastatic cells between the organs of mice.
Chapter 03 (The Researcher)
Metastasis: A Regulated Process (listen/read)
Dr. Fidler begins this segment by explaining that, in contrast with the prevailing belief (in the 70s) that cancer is the “ultimate expression of cellular anarchy” and that metastasis is random, his work has shown that cancer is a regulated process along every step of the way; similarly, metastasis is predictable. In response to a question about why scientists held (and still hold to) these conventional assumptions about cancer, Dr. Fidler notes how difficult it can be for a scientific community to accept innovative ideas. He then talks about significance of training clinicians in research and the basic sciences.
Chapter 04 (Personal Background)
Reflections on Research; Becoming a Citizen; Influences: Words of Wisdom (listen/read)
In this character-revealing segment, Dr. Fidler talks about his ability to think outside the box. He recalls becoming a citizen and some of the cross-cultural challenges he faced. He recalls family members who influenced his independent thinking. He reflects on the contributions he has made to his field and the influence of Dr. Judah Folkmann on his thinking.
He ends this session by talking about the implications of his discoveries for research, its links to the current push for individualized care. He also questions how quickly they have been translated into therapies that will benefit patients.
Interview Session Two: 27 September 2011 (listen/read)
Interview Identifier (listen/read)
Chapter 05 (The Researcher)
Recent Research: A Focus on Brain Metastasis (listen/read)
Dr. Fidler discusses his research focus for the last four years: brain metastasis. He emphasizes that very few researchers focus on brain metastasis, largely due to the complexities presented by the blood-brain barrier. Dr. Fidler explains that the blood-brain barrier is already compromised in metastasis, a fact that has implications for treating as well as studying the condition. He discusses his work on astrocytes, which protect tumor cells from chemotherapy, until he and his group discovered a drug (now patented) that interrupts the astrocyte’s protective activity.
Chapter 06 (The Researcher)
Brain Metastasis: Activating the Body’s Capacity to Heal Itself (listen/read)
Dr. Fidler begins this segment by noting his roles as the president of the International Differentiation Society and as the youngest president of the American Association for Cancer Research. He talks about how leadership of professional societies. He then returns to a discussion of the mechanisms of brain metastasis. He notes that the death of his friend, Judah Folkman, led him to re-evaluate his life and step down from his administrative responsibilities, a move that left him with more time to think about his research and investigate the role of astrocytes. He believes that intervening in the role of astrocytes in interacting with the genetics of metastatic cells has implications for treatment of many different diseases as well as other forms of cancer. He then turns back to a discussion of his work on activating macrophages to attack metastasis, quoting from “The Doctor’s Dilemma,” a play by George Bernard Shaw (1911), to dramatize that the body has all it needs to cure itself: “Nature has provided in the white corpuscle… a natural means of devouring and destroying all disease and germs…. Drugs are a delusion.”
Chapter 07 (The Researcher)
Translational Research at MD Anderson (listen/read)
Dr. Fidler explains that changes at NCI had threatened to limit his research freedom and motivated his move in 1983 to MD Anderson, where collaboration with clinicians was fostere his main goal at that time was to understand metastasis at a clinical level. He speaks about his work training clinicians, many of whom now work at MD Anderson. In the final fifteen minutes of the session, Dr. Fidler tells an amusing anecdote about how he came to occupy the R.E. “Bob” Smith Distinguished Chair in Cell Biology (as his wife, Margaret Kripke was simultaneously offered the Vivian Smith Distinguished Chair in Cell Biology). He describes his relationships training Japanese and Korean clinicians, and notes that the work at MD Anderson he is most proud of is training the next generation. He closes with an anecdote about his most significant award, though he also quotes words attributed to King Solomon: “Don’t do things for the sake of an award.”
During this interview conducted over two sessions on September 26 and 27, 2011, Dr. Isaiah J. Fidler (b. Jerusalem, Israel, 1936), focuses on the contributions he has made to advancing research on metastasis. Tacey A. Rosolowski is the interviewer. The interview takes place in Dr. Fidler’s office in the Smith Research Building on the MD Anderson South Campus. Dr. Fidler came to MD Anderson in 1983 to establish the Metastasis Research Laboratory. On display in his office are numerous awards and memorabilia, including the microscope he used when conducting his first studies on metastasis and a first-edition book by the 19th -century pathologist, Stephen Paget, who articulated the “soil and seed” theory that Dr. Fidler continues to champion as he studies interactions between differentiated cancer cells and the body sites in which they produce metastasis. Dr. Fidler is very skillful at explaining complex molecular and physiological processes. He also offers many insights into the creative process of scientific discovery, often weaving in bits of wisdom taken from eclectic sources.
Dr. Fidler is the Director of the Metastasis Research Laboratory in the Dept of Cancer Biology. He holds the R.E. “Bob” Smith Distinguished Chair in Cell Biology. He is a Professor in the Department of Cancer Biology with a joint appointment in The Department of Cancer Biology in the Graduate School of Biomedical Sciences. Dr. Fidler is known as the ‘father of modern cancer metastasis research,’ and his numerous award include: the Lifetime Achievement Award from Nature Publishing (2010); the President’s Award from MD Anderson (2007); the American Cancer Society Distinguished Service Award (2004); the 22nd Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research (1999). He was made an Honorary Member of the Japanese Cancer Association in 2007. He also received The Israel Cancer Association Award Presented by the President of Israel, the honor he says is the most meaningful to him.
In this interview, Dr. Fidler discusses his research in detailed terms, bringing great passion to the conceptual bases of his experiments: the “seed and soil” theory and the notion that cancer is a regulated and even predictable process. He discusses how his discoveries foster hope that more therapies will be discovered. He also comments on his own approaches and thought processes, providing insight into the practice of basic and translational researchers.