One interview session: 5 March 2013
Total duration: 43 minutes
Interviewer: Tacey A. Rosolowski, PhD
About the Interview Subject:
Dr. Alfred G. Knudson (b. August 9, 1922, Los Angeles, CA) served as the Dean of the Graduate School of Biomedical Sciences at the University of Texas Health Science Center from 1970 to 1976. He is best known for formulating the Two-Hit Hypothesis, which states that there must be at least two mutations, or "hits," to DNA to cause cancer. Dr. Knudson received his M.D. from Columbia University in 1947 and his Ph.D. from the California Institute of Technology in 1956. He has received a number of awards for his contributions, including the 1998 Albert Lasker Award for Clinical Medical Research, the 1999 American Society of Pediatric Hematology/Oncology Distinguished Career Award, the 2005 American Association for Cancer Research Award for Lifetime Achievement in Cancer Research, and the 2004 Kyoto Prize in Life Sciences. Dr. Knudson has worked at Fox Chase Cancer Center since 1976.
Major Topics Covered:
Educational background and military experience
Development of interest in pediatric cancer
The two-hit model: discovery and implications
Mentoring and advice for young scientists
The Graduate School of Biomedical Science: history, effects
Perspectives on the fields of cancer biology and neuroscience
Interview Session One:
Attempt to Join the Navy Leads to Medical School
Chapter 01/ Educational Path
Residency Experience Cultivates Interest in Pediatric Cancer
Chapter 02/ Professional Path
A Geneticist Pediatrician Joins the Army; Return to Cal Tech
Chapter 03/ Professional Path
A Slow Start to Creating a Genetics Unit at Stonybrook Leads to MD Anderson
Chapter 04/ Professional Path
Discovering the Two-Hit Model Through Studying Retinoblastoma
Chapter 05/ Contributions
Two-Hit Model Allows for Genetic Testing of Blood
Chapter 06/ Contributions
Work with Dr. Louise Strong
Chapter 07/ Key MD Anderson Figures
Curiosity and Asking Innovative Questions is "The Way He's Wired"
Chapter 08/ Character and Personal Philosophy
Advice for Young Researchers and Mentoring
Chapter 09/ Character and Personal Philosophy
Becoming the Dean of the Graduate School of Biomedical Sciences at MD Anderson
Chapter 10/ Building the Institution
The Graduate School: An "Amazing Experiment" in Sub-Institutional Collaboration
Chapter 11/ Building the Institution
Perspectives on the Fields of Cancer Biology and Neuroscience
Chapter 12/ Overview
Interview Session One: (listen/read)
Interview Identifier (listen/read)
Chapter 01 (Education Path)
Attempt to Join the Navy Leads to Medical School (listen/read)
Education: Dr. Knudson discusses his switch from physics to genetics in his second year at the California Institute of Technology. He humorously notes that he made the change because "they already knew everything" in the field of physics. He mentions that Thomas Hunt Morgan, a pioneer in genetic research, was the head of the Biology department at Cal Tech at the time.
Military Experience: Dr. Knudson then explains that at the start of World War II, Cal Tech encouraged its students to join the military, so he enlisted in the navy. However, a person in the navy encouraged Dr. Knudson to go to medical school instead because they "didn't need PhDs in the military." He took their advice and went to Columbia Medical School. Dr. Knudson says that he enjoyed the first two years more than the second because they were based on problem solving rather than memorization.
Mentoring: In the last moments of the chapter, Dr. Knudson provides some advice to young people on how to approach unexpected events in life.
Chapter 02 (Professional Path)
Residency Experience Cultivates Interest in Pediatric Cancer (listen/read)
Interest in Cancer: Dr. Knudson sketches the development of his interest in cancer. He notes that during medical school, he did not learn about cancer because there was no real treatment for cancer at the time. His interest came through his residency in pediatrics at New York Hospital, where he completed a month-long rotation in the children's cancer unit at Memorial Hospital. Dr. Knudson explains the impact this experience had on him.
Chapter 03 (Professional Path)
A Geneticist Pediatrician Joins the Army; Return to Cal Tech (listen/read)
Military Experience: Dr. Knudson talks about his enlistment in the army during the Korean War. He was supposed to spend a year in Korea and a year in the U.S. Instead, he spent two years in Fort Riley, Kansas because the army was not sure what to do with a geneticist pediatrician in Korea.
Education: Dr. Knudson then discusses his return to the California Institute of Technology in 1953 to study. He briefly talks about the influence of Watson and Crick's work on the field of genetics earlier that year. After he finished at Cal Tech, Dr. Knudson was put in charge of a small pediatrics unit at City of Hope Medical Center, which fit his previous experiences well.
Chapter 04 (Professional Path)
A Slow Start to Creating a Genetics Unit at Stonybrook Leads to MD Anderson (listen/read)
Interest in Cancer: Dr. Knudson continues outlining his path towards discovering the two-hit model. He explains that during his time at City of Hope Medical Center, he became more interested in cancer and hereditary predisposition and was asked to write a book on genetics and disease. Dr. Knudson notes that although this work helped him to put the cancer problem in perspective, it was too early for him to discover the two-hit model.
Administrative Experience: Next, Dr. Knudson recalls his frustrations about his slow-moving experience starting a genetics unit at Stonybrook in New York. After three years at Stonybrook, Dr. Knudson accepted an invitation to come to MD Anderson to start a genetics unit.
Chapter 05 (Contributions)
Discovering the Two-Hit Model Through Studying Retinoblastoma (listen/read)
R. Lee Clark's Influence: Dr. Knudson reflects on the environment of MD Anderson under R. Lee Clark's presidency, saying that "Lee didn't understand [the word] 'can't.'" Dr. Knudson explains that Clark asked him to write a review article for a journal, which forced him to think about what kind of gene is important in cancer. He notes that research on cancer was mostly done on adult cancer, but children's cancer is important for answering that question.
Overview of Two-Hit Model: Dr. Knudson then describes how he discovered the two-hit model. Muller published a paper claiming that several steps are necessary to make cancer. Though the literature after Muller's paper attempted to figure out those steps, Dr. Knudson wanted to know what the smallest number of events could be. He explains that his experience in pediatrics led him to look at retinoblastoma, a cancer with a hereditary form, to figure out the problem. Through statistical studies, Dr. Knudson concluded that the smallest number of events is two.
Chapter 06 (Contributions)
Two-Hit Model Allows for Genetic Testing of Blood (listen/read)
Contributions: Dr. Knudson discusses how the two-hit model influenced research by opening the possibility of testing for the gene in patients' blood. He explains that this is useful for adults who had childhood cancer who want to know the likelihood of passing on the cancer to their children. Dr. Knudson mentions that the two-hit model additionally called attention and interest to other hereditary cancers.
Research Reflections: Dr. Knudson then reflects on the research process that led to the two-hit model, saying that he was lucky that retinoblastoma gave a quick answer to the problem.
Chapter 07 (Key MD Anderson Figures)
Work with Dr. Louise Strong (listen/read)
Mentoring Experience: Dr. Knudson did not have much experience with trainees, because most of his work was theoretical. He discusses one meaningful experience with a young woman who asked to work in his lab. At that time, he had just arrived at MD Anderson and had not started to study retinoblastoma. Dr. Knudson says that after he wrote his paper on the two-hit model, he called the woman and invited her to work with him. The woman's name was Louise Strong.
Portrait of Dr. Strong: Dr. Knudson then tells an amusing anecdote about Dr. Strong. He describes the work that they completed together, reviewing the literature on tumors and publishing papers together. Dr. Knudson concludes by saying that he offered Dr. Strong an assistant professor position, which she accepted.
Chapter 08 (Character and Personal Philosophy)
Curiosity and Asking Innovative Questions is "The Way He's Wired" (listen/read)
Personal Character: When asked about how he developed his innovative style to problem solving, Dr. Knudson responds by saying that it is not a conscious decision. He states that a lot of people have an attraction to the unknown and are curious. The interviewer reveals that Dr. Strong remembered Dr. Knudson asking innovative questions from a diverse background and asks if he is aware of that characteristic. Dr. Knudson says that it is just the way he is.
Chapter 09 (Character and Personal Philosophy)
Advice for Young Researchers and Mentoring (listen/read)
Advice for Young Scientists: Dr. Knudson says that young scientists need curiosity, intelligence, and training to be successful.
Critical Perspectives: He then critiques the state of funding for scientists. He discusses the drop in funding from the NIH and points out that back in the 1960s, a handful of grants were approved that probably wouldn't work, but would be monumental if they did work. Now, he says, those projects are never funded. Dr. Knudson believes that too many grants are doing predictable research and not enough are surprising.
Perspectives on Research: Dr. Knudson then reiterates that to be successful, a scientist needs curiosity. He notes that he has never known a person conducting scientific research for a long time who regretted it. He additionally states that although physician scientists may benefit from seeing direct benefits from their work, some research may not be immediately beneficial to anyone, such as Einstein's work. Dr. Knudson declares that the greatest thing that humans can do is have new ideas. He says that people may come and go, but knowledge keeps building.
On Mentoring: Dr. Knudson outlines what students should expect from a mentor, saying that a mentor should minimally be able to identify whether a project is worthwhile. He notes that this impacts where a student should go, because some problems may not be able to be studied everywhere.
Chapter 10 (Building the Institution)
Becoming the Dean of the Graduate School of Biomedical Sciences at MD Anderson (listen/read)
Administrative Experience: Dr. Knudson outlines how he became dean of the Graduate School of Biomedical Sciences. He says that R. Lee Clark asked him to start a genetics program. As soon as he arrived, the plans changed because the medical school was created and would include a genetics program. He states that Clark believed the answer was the graduate school. Dr. Knudson explains that Clark persuaded him to become the dean. He notes the difference between MD Anderson and Stonybrook, where everything moved slowly.
Chapter 11 (Building the Institution)
The Graduate School: An "Amazing Experiment" in Sub-Institutional Collaboration (listen/read)
Education at MD Anderson: Dr. Knudson explains that the graduate school affected students by increased the faculty, which increased the student body as well. It also provided opportunities outside of the field of cancer. Dr. Knudson says that the dean of the medical school went along with this new graduate school. The School of Public Health additionally got involved in the collaboration. Dr. Knudson states that the graduate school was an "amazing experiment" because they went beyond what graduate schools typically do.
Effects of the Graduate School: Dr. Knudson admits that he has not kept track of the graduate school much over the years. When asked about the interdisciplinarity within the school and how it can prepare students, Dr. Knudson says that it is good for students to get a broad basis of understanding because new fields are appearing all of the time. He believes that understanding the human brain and what it can do is the future.
Chapter 12 (Overview)
Perspectives on the Fields of Cancer Biology and Neuroscience (listen/read)
On Cancer Biology: Dr. Knudson reflects on the field of cancer biology. He says that knowing the genetic changes that can occur in cancer is important because different cancers have different cures. He presents radiation and chemotherapy as an example. Dr. Knudson additionally points out that leukemia did not use to have a treatment, but now, there are long-living survivors of leukemia. He explains how adult cancer is more challenging to cure than children's cancer.
On Neuroscience: Dr. Knudson talks about his interest in neuroscience when asked about which field he would chose if he was a young scientist today. He then explains that cancer and degenerative diseases will always exist because of the nature of the cells in the human body.