Four interview sessions: 21 May 2014, 29 May 2014, 4 June 2014, 18 June 2014
Total approximate duration, 5 hours 30 minutes
Interviewer: Tacey A. Rosolowski, Ph.D.
About the Interview Subject:
Dr. Eugenie Kleinerman (b. 16 April 1949, Baltimore, Maryland) was recruited to MD Anderson in 1984 as an Assistant Professor in the Department of Pediatrics. Today she holds the Mary V. and John A. Reilly Distinguished Chair. She also has a joint appointment with the Department of Cancer Biology.
Dr. Kleinerman is best known as a pioneer in the use of immunological treatments for osteosarcoma. Her first discoveries involved the agent, MEPACT, and she has gone on to investigate many agents, combination therapies, and novel delivery systems.
As Head of Pediatrics at MD Anderson, a role she has served since 2001, Dr. Kleinerman established an oncology services specifically designed for pediatric patients, and was successful in establishing their unique identity in the “hospital within a hospital,” the Children’s Cancer Hospital.
Major Topics Covered:
Personal and educational background
Women in medicine and at MD Anderson
Areas of research; development of her translational approach
History of translational research at MD Anderson
Leading the Division of Pediatrics
Views on change at MD Anderson with shifts in executive leadership
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.
Interview Session One: 21 May 2014
MD Anderson Culture and Faculty
Chapter 1 / Overview
MD Anderson Culture and Faculty: In Transition with a New Administration
Chapter 2 / Institutional Change
Focused on Medicine; Navigating Institutions without Mentors
Chapter 3 / Educational Path
Medical School, A Fellowship, and A First Research Project
Chapter 4 / Professional Path
Bringing Clinical and Laboratory Experience Together and Identifying a Research Focus
Chapter 5 / The Researcher
Leaving the NCI for Research at MD Anderson
Chapter 6 / Joining MD Anderson/Coming to Texas
Interview Session Two: 29 May 2014
An Introduction to MEPACT and a New Research Collaborator for Study of Osteosarcoma Treatment
Chapter 7 / The Researcher
Putting the Pieces in Place to Do a Phase I Trial with MEPACT
Chapter 8 / The Researcher
Designing a Phase II Trial for MEPACT, and the Characteristics of Translational Research
Chapter 9 / The Researcher
A Pioneering Attitude at MD Anderson: The Nature of Translational Research and The Physician-Scientist --a ‘Dying Breed’
Chapter 10 / MD Anderson Culture
A Successful Phase III Trial and European Approval, But No FDA Approval for MEPACT
Chapter 11 / The Researcher
Interview Session Three: 4 June 2014
Innovative Aerosol Therapy for Bone Metastasis to the Lung and An Overview of Translational Research
Chapter 12 / The Researcher
Mesenchymal Stem Cell Treatment for Ewing’s Sarcoma; Harnessing Autophagy to Reduce Tumors
Chapter 13 / The Researcher
Challenges to the Division of Pediatrics
Chapter 14 / Building the Institution
The MD Anderson Children’s Cancer Hospital; Creating a Successful Training Program
Chapter 15 / Building the Institution
Interview Session Four: 18 June 2014
Developing the Division of Pediatrics
Chapter 16 / Building the Institution
Plans to Develop The Division of Pediatrics
Chapter 17 / Building the Institution
Women at MD Anderson and Becoming a Leader
Chapter 18 / Diversity Issues
Leadership, Leaders, and Concerns For MD Anderson
Chapter 19 / Critical Evaluation
Privileged to Work at MD Anderson; An Active Life and Family
Chapter 20 / Personal Background
Interview Session One: 21 May 2014 (listen/read)
Interview Identifier (listen/read)
Chapter 1 (Overview)
MD Anderson Culture and Faculty (listen/read)
Dr. Kleinerman begins this chapter by explaining that she came to MD Anderson from the NCI in the early eighties because she was interested in running clinical trials with children diagnosed with osteosarcoma, and was unable to do so at the NCI. She recalls her colleagues’ reactions when she said she was going to Texas and notes that despite the growth of MD Anderson’s reputation, there is a lingering perception that the institution is not as good as those in the East and in California. She tells an anecdote that indicates the perception that “we’re yokels.” She notes that MD Anderson never aspired to have the same structure as an academic institution because of the strong focus on cancer and translational research. “We don’t want to be a Harvard, a Yale, a Stanford.”
Chapter 2 (Institutional Change)
MD Anderson Culture and Faculty: In Transition with a New Administration (listen/read)
Dr. Kleinerman offers observations on how the culture of MD Anderson has been changing since the arrival of MD Anderson’s fourth president, Dr. Ronald DePinho. She sets context by describing the impact of a change instituted by Dr. John Mendelsohn, M.D. [Oral History Interview]: requiring faculty to derive 30% of their salaries from grants, with this rising under the new administration.
She discusses concerns that the institution is no longer distributing value equally between basic science research, clinical research, teaching and mentoring. She also fears the loss of a “special atmosphere” of collaboration and collegiality as well as innovation that the older system fostered. She demonstrates the support for innovation using her own innovative study of immune-therapy in children, an atmosphere that allowed her to conduct research impossible at the NCI.
Dr. Kleinerman next explains that today the institution is more rigid and rule-governed, with a strong focus on genomics.
Chapter 3 (Educational Path)
Focused on Medicine; Navigating Institutions without Mentors (listen/read)
Dr. Kleinerman traces her educational path up to medical school.
Dr. Kleinerman begins by sketching her family background and notes her father’s role as her
first mentor. She describes experiences that inspired her to be a physician-researcher from the age of five.
She next sketches her path to Washington University (St. Louis, Missouri, BA 1971, Biology). She describes instances of gender bias that left her without a mentor to help her navigate the college environment. She notes that she became accustomed to not being taken seriously and credits her mother with providing her with determination. She also sets her experience in the context of the cultural environment of the 1960s. Dr. Kleinerman notes that she married Leonard Zwelling, MD (while in medical school) in 1972, describing the assumption on the part of colleagues that she would then become less serious about her career.
Chapter 4 (Professional Path)
Medical School, A Fellowship, and A First Research Project (listen/read)
Dr. Kleinerman traces her path to medical school and into her clinical fellowship (1974−1975 Clinical Fellowship, Rheumatology, Duke University).
She first explains the process of getting into medical school at Duke University, Durham, North Carolina (MD 1974). She describes the curriculum and notes that the small number of women. She explains her view of different specialties and her selection of pediatrics. She recalls instances of gender bias encountered, then describes how she met Dr. Ralph Snyderman, who was instrumental in introducing her to immunology and setting up her collaboration on a research project conducted during her clinical fellowship in the rheumatology laboratory. She then talks about how her research results were controversial. She concludes with additional memories of gender bias.
Chapter 5 (The Researcher)
Bringing Clinical and Laboratory Experience Together and Identifying a Research Focus (listen/read)
Dr. Kleinerman notes that her fellowship in clinical research had enabled her to secure national recognition. She then spent three years focusing on clinical practice at Children’s Hospital National Medical Center in Washington, DC. She explains how this helped her later research career when it came to identifying treatment for patients. She also describes going to see the film, “Promises in the Dark,” an experience that influenced her decision to focus on oncology.
Dr. Kleinerman then explains how she took a position as a Clinical Associate in the Metabolism Branch of the NCI Bethesda (1978−1981), where she met Isaiah Fidler, DVM, PhD [Oral History Interview], who was working on immune therapy for lung metastasis, research she felt could work for osteosarcoma. Dr. Fidler would become her mentor.
Chapter 6 (Joining MD Anderson/Coming to Texas)
Leaving the NCI for Research at MD Anderson (listen/read)
Dr. Kleinerman begins with stories to demonstrate that she was not taken seriously as a researcher at the NCI. She explains that when Dr. Fidler left the NCI for MD Anderson, he brought her with him. She recalls interactions with Norman Jaffe, MD (Oral History Interview), and notes that she never had to prove herself with him. She also notes that she was the first person to do clinical research in pediatrics.
Dr. Kleinerman next describes the climate for women in the institution when she arrived in 1984.
[The recorder is paused for 2 minutes.]
Interview Session Two: 29 May 2014 (listen/read)
Interview Identifier (listen/read)
Chapter 7 (The Researcher)
An Introduction to MEPACT and a New Research Collaborator for Study of Osteosarcoma Treatment (listen/read)
Dr. Kleinerman speaks in detail about her pioneering work on the immunotherapy agent, liposomal muramyl tripeptide –MTPE.
She describes the drug and the mechanisms of its interaction with macrophages, as well as the technique she used to sheath the drug in lipids that would result in attacks on cancer cells. She sketches Dr. Isaiah Joshua Fidler’s [Oral History Interview] work on this agent in mice and describes her “Eureka moment” in understanding the implication of his results for osteosarcoma. She also talks about her first interaction with Dr. Fidler, whose reaction to her idea was “Let’s collaborate.” She explains why she was a good partner for him in translational research.
Next Dr. Kleinerman explains why the NCI was resistant at the time to running clinical trials on children. Sketches her own experience with osteosarcoma and how she discovered that the disease, though rare, is a big problem.
Chapter 8 (The Researcher)
Putting the Pieces in Place to do a Phase I Trial with MEPACT (listen/read)
Dr. Kleinerman begins the MEPACT story by discussing her growing collaboration with Dr. Fidler.
She explains the preliminary work required before running a human trial involving the immunotherapy agent, MEPACT. She talks about partnering with Ciba Geigy.
Next, Dr. Kleinerman explains how an individual at the NCI blocked her attempts to develop a trial, noting possible gender bias, followed by Dr. Fidler’s invitation for her to come with him to MD Anderson.
Dr. Kleinerman explains her strategy of constructing “the ultimate clinical protocol.” She describes the ethical issues that arose and research challenges in determining the Optimal Biological Dose (OBD). She notes that she and Dr. Fidler were the first to design a study around this concept and that they have not been adequately recognized for this contribution. She notes that they also ran studies to demonstrate that human patients could respond to the drug.
Next Dr. Kleinerman notes that in 1986 with support of colleagues at MD Anderson. She describes the results and some surprising discoveries.
Chapter 9 (The Researcher)
Designing a Phase II Trial for MEPACT, and the Characteristics of Translational Research (listen/read)
In this Chapter, Dr. Kleinerman tells the next part of the MEPACT story: designing a Phase II trial. She sketches the practical elements of submitting a proposal and notes ways in which it was innovative.
Dr. Kleinerman explains how she designed the Phase II trial and the unusual parameters she set for selection patients. “I was one of the cowboys at MD Anderson.” Dr. Kleinerman explains that MD Anderson had a culture of using pioneering approaches to treat cancer.
Dr. Kleinerman describes the protocol and some surprising initial results that came from the Phase II trial and demonstrated the effectiveness of MEPACT on pulmonary metastases.
Chapter 10 (MD Anderson Culture)
A Pioneering Attitude at MD Anderson: The Nature of Translational Research and The Physician-Scientist --a ‘Dying Breed’ (listen/read)
Dr. Kleinerman begins by explaining that she looked at problems differently because of her basic sciences background. She then explains her view that physician-scientists are a dying breed, and goes on to explain her definition of translational research and important a physician’s perspective is to it.
Picking up a thread of the discussion about MD Anderson culture in Session I, she explains that closing clinicians out of research is a “national tragedy” created by the decreases in money available for funding. She observes that before Dr. Ronald DePinho assumed the presidency of MD Anderson, the institution held the attitude that it was unique and did not want to rely on external systems to validate the research conducted within the institution.
Chapter 11 (The Researcher)
A Successful Phase III Trial and European Approval, But No FDA Approval for MEPACT (listen/read)
In this chapter, Dr. Kleinerman brings the MEPACT story to a close.
She first describes how the Pediatric Oncology Groups of the NCI first had a very negative reaction to the results of the Phase II trial, then explains why this turned around. Dr. Kleinerman worked with collaborators to design a Phase III trial. She describes practical and political complexities that resulted in the FDA not approving MEPACT, despite its efficacy.
Dr. Kleinerman next explains the process that won approval for MEPACT from the European Medical Association, where her work defined has become standard of care in the United Kingdom.
Dr. Kleinerman discusses FDA approval processes.
In the final moments of this Chapter, Dr. Kleinerman talks about the impact that clinical trials can have on faculty careers, when it takes years to achieve results.
Chapter 12 (The Researcher)
Innovative Aerosol Therapy for Bone Metastasis to the Lung and an Overview of Translational Research (listen/read)
In this chapter, Dr. Kleinerman describes her work on a novel aerosol therapy for bone metastasis to the lung, weaving in explanations of biological and genetic processes as well as overviews of work in the field.
She explains that her research approach begins with understanding the disease and then she looks for novel alternatives to chemotherapy. She outlines the science involved in this study then sketches the phases of research she developed.
Dr. Kleinerman summarizes how she took basic science and clinical knowledge to development treatment, then gives an overview of her philosophy of translational research and the evolution of this kind of work at MD Anderson.
At the end of this chapter, Dr. Kleinerman talks about the advantages of aerosol therapy for patients.
Chapter 13 (The Researcher)
Mesenchymal Stem Cell Treatment for Ewing’s Sarcoma; Harnessing Autophagy to Reduce Tumors (listen/read)
In this chapter, Dr. Kleinerman talks about her interest in the rare cancer, Ewing’s sarcoma. She first sketches the research questions she poses, based on the tumor’s reliance on blood vessels. She sketches how she focused on mesenchymal stem cells and a pathway to block to successfully prevent angiogenesis, turning this cancer into a chronic disease. Dr. Kleinerman notes some challenges to doing clinical trials, then comments on her approaches to clinical problems and the importance of funding for basic research.
Next Dr. Kleinerman talk about a new area of research she has undertaken harnessing the process of autophagy.
Chapter 14 (Building the Institution)
Challenges to the Division of Pediatrics (listen/read)
In this chapter, Dr. Kleinerman talks about her activities as Head of the Division of Pediatrics.
She explains how she came to be Division Head in 2001. She sketches the history of pediatric care at MD Anderson. She says that when she arrived at MD Anderson in 1984, it was challenging to care for pediatric patients in an adult facility. Dr. Kleinerman provides an overview of what is needed for pediatric care.
Next, Dr. Kleinerman talks about measures she first took as Division Heaholding a strategic planning retreat, developing a vision, hiring critical care staff. She talks about the process of gaining the trust of the faculty, then goes into more detail about the retreat and her strategies for developing the strength of the faculty. She gives an example of shifting the responsibilities of a faculty member who was suffering from burnout, enabling him to perform more effectively. She also notes that, with the new administrative (and billing) structures in place, it is not possible to use such creative approaches to problems.
Chapter 15 (Building the Institution)
The MD Anderson Children’s Cancer Hospital; Creating a Successful Training Program (listen/read)
Dr. Kleinerman begins this chapter by discussing her working relationship with Dr. John Mendelsohn, MD [Oral History Interview], who supported her efforts to develop pediatric care. She notes that Dr. Mendelsohn formed an Advance Team composed of Board of Visitors members to advise Dr. Kleinerman on strategy to develop Pediatrics. Their main advice: “You need a separate name,” and in 2005 Pediatrics received their designation of the Children’s Cancer Hospital. She describes initiatives arising from this.
Next, Dr. Kleinerman explains that at the same time, she was building the faculty. She acknowledges that faculty were leaving because of conflict with her new focus on innovative research and research productivity. She notes that she recruited about 75% of the current faculty and describes the active networking required to identify good candidates.
Dr. Kleinerman next sketches her vision for the future of the Division then talks in more detail about the successful Fellowship program that she initiated twelve years ago.
Interview Session 4: 18 June 2014 (listen/read)
Interview Identifier (listen/read)
Chapter 16 (Building the Institution)
Developing the Division of Pediatrics (listen/read)
Dr. Kleinerman discusses the growth of the Division of Pediatrics and the need to further develop services for adolescents and young adults.
She explains the business plan she developed at Dr. David Callender’s request when she assumed leadership of the Division.
Next she discusses the design of the Children’s Cancer Hospital opened in 2013 and the four advisory councils created to help guide the design and staffing.
Next, Dr. Kleinerman explains the need to develop services for adolescents and young adults (particularly in the area of fertility counseling) and explains why pediatrics is attuned to the special needs of patients. She talks about a failed attempt to open a special lounge area for this group.
Chapter 17 (Building the Institution)
Plans to Develop The Division of Pediatrics (listen/read)
Dr. Kleinerman talks about several areas she is working on to build the Division.
She notes challenges in developing research areas. She explains difficulties in enrolling children in Phase I clinical trials and the need to develop the Survivorship Program. Dr. Kleinerman then talks about her desire to have an impact on Supportive Care.
Next Dr. Kleinerman talks about the Family Advisory Council and gives specific examples of how the Council provides guidance as programs and units are developed. She observes that the Division of Pediatrics is attempting to preserve a primary care model of care delivery while also working for more efficiency. She notes the influence of institutional silos on survivorship and family-centered care issues.
Next Dr. Kleinerman talks about the need to develop translational research on cell therapy and transplantation. At the end of this Chapter, Dr. Kleinerman comments on lessons about leadership she has learned.
Dr. Kleinerman notes the absence of women leaders at MD Anderson. She then talks about the benefits of living in Houston. She tells stories to demonstrate the support she had as a working mother and the welcoming attitude of the Jewish community in Houston.
Chapter 18 (Diversity Issues)
Women at MD Anderson and Becoming a Leader (listen/read)
Dr. Kleinerman begins this chapter by talking about the respective responsibilities of mentors and mentees. She tells a story about a regular dinner support-group of women faculty. Dr. Kleinerman describes the different ways that male and female faculty members approach her for mentoring.
Next, she talks about efforts to develop the visibility of women at MD Anderson around the time when she arrived. She describes issues she wanted to push forwara day care center and a four-day work week option. She observes that the community of woman at MD Anderson has become stronger, but otherwise there is no movement to change the culture for women at the upper levels of the institution.
Dr. Kleinerman next sketches what women bring to leadership. She quotes Dr. Isaiah “Josh” Filder [Oral History Interview] who says that it will take men recognizing the situation to change it.
Chapter 19 (Critical Evaluation)
Leadership, Leaders, and Concerns For MD Anderson (listen/read)
Dr. Kleinerman begins this chapter by talking about how her view of her self as a leader has evolved through lessons learned. She talks about how she identifies and develops potential leaders. She also cites wisdom she has learne“You have to be ready to bask in reflected glory,” and offers the view that president of the institution, Ronald DePinho, MD, is a “negative example” of that kind of leadership. Next Dr. Kleinerman talks about changes in MD Anderson culture under Dr. DePinho’s leadership and expresses concerns that “we are losing a lot of our soul.” Dr. Kleinerman then offers perspectives on Dr. Charles A. LeMaistre [Oral History Interview] and Dr. John Mendelsohn [Oral History Interview].
Chapter 20 (Personal Background)
Privileged to Work at MD Anderson; An Active Life and Family (listen/read)
Dr. Kleinerman begins by talking about the “privilege” she feels to work at MD Anderson. Next she lists the initiatives she would like to be remembered for. She then talks about her family life and active personal life.