Skip to main content

Plunkett (William), PhD, Oral History Interview: Home

Interview Navigation Materials

Interview Navigation Material

 

Interview Profile

Submitted: 9 July 2014

 

Interview Information:

Three interview sessions: 25 March 2013, 10 April 2013, 8 May 2013
Total approximate duration: 6 hours and 30 minutes
Interviewer: Tacey A. Rosolowski, Ph.D.

 

For supplementary materials:

Please contact, the Historical Resources Center, Research Medical Library:

Javier Garza, MSIS, jjgarza@mdanderson.org

 

About the Interview Subject:

William Plunkett, Ph.D. (b. Boston, 4 May 1943), came to MD Anderson in 1975 as an Assistant Biochemist in the Department of Developmental Therapeutics.  He joined the faculty of that Department as an Assistant Professor later that year.  He is now a full professor in the Department of Experimental Therapeutics and has a joint appointment in the Department of Leukemia. Dr. Plunkett’s research has focused on the study of the cellular mechanisms of tumor viability.  He has examined the roles of nucleoside analogues, fludarabine and gemcitabine, as well as mechanisms of cell apoptosis.  His translational collaborations result in innovative strategies to kill tumor cells.  He a co-director of the Moon Shot Program devoted to Chronic Lymphocytic Leukemia. 

Since 2008 Dr. Plunkett has served as Deputy Chair of the Department of Experimental Therapeutics.  Prior to this, from 1993−2004 he served as Chief of the Section of Cellular & Molecular Pharmacology, Department of Experimental Therapeutics, then as the Department’s Director of Research Development from 2005−2008.  

 

Major Topics Covered:

Personal and educational background

View of history of biomedical sciences; evolution of team science

Research: nucleoside analogues; gemcitabine, fludarabine; mechanisms of cell death, DNA repair

Research collaborations: with Pharma; importance of collegiality; inter-disciplinary discussions

The CLL Moon Shot Program

The Department of Developmental Therapeutics

Memories of Emil J Freireich, MD

The Department of Experimental Thereutics: origin of; strategic plan for; training initiatives; department culture

MD Anderson’s Conflict Resolution Process

Research Integrity Officer: roles; cases, research issues; ethics

MD Anderson executive leadership: views on

 

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.


 

 

 

Table of Contents

 

Interview Session One: 25 March 2013

 

A Time of Change in the Sciences
Chapter 01 / Educational Path

 

Focusing a Research Career
Chapter 02 / The Researcher

 

An Interest in Therapeutic Applications and a Job Offer from J Freireich
Chapter 03 / Joining MD Anderson/Coming to Texas

 

Basic and Clinical Researchers in Conversation at MD Anderson
Chapter 04 / The Researcher

 

Working on Nucleoside Analogues
Chapter 05 / The Researcher

 

Drug Studies (and How Collegiality Can Move Them Along)
Chapter 06 / The Researcher

 

Co-Director of the Leukemia Moon Shots Program
Chapter 07 / The Administrator

 

Interview Session Two: 10 April 2013

 

Working with Fludarabine; The Importance of Extra-Institutional Connections and Ethics
Chapter 08 / The Researcher

 

The CLL Moon Shot Program
Chapter 09 / An Institutional Unit

 

Team Science and Training Team Scientists
Chapter 10 / The Administrator

 

Mentoring, Education, and Team-Science Culture
Chapter 11 / The Administrator

 

Research with Gemcitabine
Chapter 12 / The Researcher
 

 

Exploiting Cell Death Mechanisms and DNA Repair to Kill Tumor Cells
Chapter 13 / The Researcher

 

Interview Session Three: 8 May 2013

 

 Developmental Therapeutics and the Origin of The Department of Experimental Therapeutics
Chapter 14 / An Institutional Unit

 

Reorganizing Developmental Therapeutics:  The Challenge of Naming Experimental Therapeutics
Chapter 15 / Institutional Change
 

 

The Department of Experimental Therapeutics: a Strategic Plan for the Department
Chapter 16 / Building the Institution

 

Faculty Senate and the Revised Conflict Resolution Process
Chapter 17 / The Administrator

 

Conflict of Interest: MD Anderson Faculty and Presidents
Chapter 18 / Overview

 

Research Integrity Officer
Chapter 19 / The Administrator

   

Skills and Support for New Research
Chapter 20 / The Researcher
 

 

MD Anderson Presidents
Chapter 21 / Key MD Anderson Figures

 

J Freireich’s Impact and A Career Commitment to Collaborative Work
Chapter 22 / View on Career and Accomplishments


 

 

Chapter Summaries

 

 

Interview Session One: 25 March 2013 (listen/read)

 

Chapter 00A
Interview Identifier (listen/read)

 

Chapter 01 (Educational Path)
A Time of Change in the Sciences (listen/read)

 

Topics Covered

  • Character, Values, Beliefs, Talents
  • Personal Background
  • Professional Path
  • Inspirations to Practice Science/Medicine
  • Influences from People and Life Experiences
  • The Researcher
  • Evolution of Career
  • On Research and Researchers
  • The History of Science, Cancer Research

Dr. Plunkett briefly sketches his family history.  (His father was a research technician at a metals laboratory in Milton, Massachusetts, and Dr. Plunkett still has a titanium chalice his father made for him.)  He then discusses his educational path, beginning with his undergraduate years at Springfield College, where he heard Dr. Frances Crick speak about DNA.  He explains his decision to focus on biochemistry when he was in graduate school at Amherst and describes the vibrant atmosphere of experimentation during this period when the biological sciences were in ferment. Dr.  Plunkett then describes how the evolving science of molecular biology spurred the understanding of genetics.

 

Chapter 02 (The Researcher)
Focusing a Research Career (listen/read)

 

Topics Covered

  • The Researcher
  • Professional Path
  • Formative Experiences
  • Influences from People and Life Experiences
  • Definitions, Explanations, Translations
  • Professional Practice
  • The Professional at Work
  • Evolution of Career
  • Mentoring
  • On Research and Researchers
  • The History of Science, Cancer Research

In this chapter, Dr. Plunkett talks about key events that focused his research career, beginning with a competitive summer research fellowship in Physiology he was able to secure at the Biological Laboratory at Woods Hole, Massachusetts.  He describes the cutting edge work being done and the mentorship he received.  He goes on to talk about several mentors who had an impact on his career including Seymour Cohen (Univ. of Pennsylvania) and Bud Moner at Amherst who was very open to Dr. Plunketts interest in purifying and classifying enzymes.   He gives a portrait of Seymour Cohen, giving a brief history of how Cohen moved from U. Penn to the University of Colorado Medical Center in Denver, inviting Dr. Plunkett to join him.  Dr. Plunkett next describes the work he conducted in Colorado on nucleoside analogues (offering a definition of these molecules) and noting other researchers influential in this research area at the time.

 

Chapter 03 (Joining MD Anderson/Coming to Texas)

An Interest in Therapeutic Applications and a Job Offer from J Freireich (listen/read)

 

Topics Covered

  • The Researcher
  • Professional Path
  • Overview
  • Definitions, Explanations, Translations
  • Funny Stories
  • Joining MD Anderson
  • Portraits
  • MD Anderson History

Dr. Plunkett begins this chapter explaining the growth of his interest in therapeutic applications of biochemistry. He defines nucleoside analogues, the focus of his research throughout his career.

Dr. Plunkett describes how Dr. Cohen brought an influential researcher in for a site visit: this was how Dr. Plunkett met Emil J Freireich [Oral History Interview] from MD Anderson and, during their brief interaction, received an invitation to come and work at MD Anderson.  Dr. Plunkett describes Dr. Freireich’s skills as an analytical listener, going on to explain the structure of the Department of Developmental Therapeutics and Dr. Freireich’s role as one of its founders and a mentor to an entire generation of scientists. 

Dr. Plunkett next explains some bureaucratic obstacles that had to be dealt with before he could be hired at MD Anderson.  He also sketches the institutional restructuring that took place in 1983 under the leadership of Dr. Charles LeMaistre and observes that this move allowed clinical people to move into more leadership roles.

 

Chapter 04 (The Researcher)
Basic and Clinical Researchers in Conversation at MD Anderson (listen/read)

 

Topics Covered

  • The Researcher
  • Professional Path
  • Overview
  • Definitions, Explanations, Translations
  • Funny Stories
  • Joining MD Anderson
  • Portraits
  • MD Anderson History
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • MD Anderson Culture
  • Professional Practice
  • The Professional at Work
  • MD Anderson Past
  • Collaborations
  • On Research and Researchers

Dr. Plunkett discusses the position of basic scientists in an institution where clinical investigators have more of a voice.  He lists the series of individuals who have headed the Division of Medicine and sketches the history of the Department of Experimental Therapeutics.  He notes that he and his colleagues have never had a department leader from the basic sciences who would make the cases on their behalf. He then sketches the evolution of the relationship between basic and clinical researchers, beginning in ’75, when Dr. Emil Freireich established the weekly meeting of specialties (sometimes with 40-50 people) to discuss how to treat solid tumors, hematologic malignancies, and other cancers.  He describes the (sometimes emotional) character of the meetings. He tells an anecdote about the role of statisticians in presenting analysis of data. He notes that the meetings influenced the design of investigations and led Dr. Michael Keating to set up a database for the Department of Leukemia. Dr. Plunkett then talks about how basic and clinical scientists worked together, first describing the receptive mindset necessary for collaboration.  He demonstrates with an example from studies of drugs to treat hematologic malignancies. Dr. Plunkett describes how much more easily scientists could get research proposals approved in the seventies.  Then he explains the symbiotic relationship between basic and clinical researchers, where clinicians need a basic science foundation to confirm their clinical findings (giving clinical research “street cred”).

 

Chapter 05 (The Researcher)
Working on Nucleoside Analogues (listen/read)

 

Topics Covered

  • The Researcher
  • Overview
  • Definitions, Explanations, Translations
  • MD Anderson History
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • MD Anderson Culture
  • Professional Practice
  • The Professional at Work
  • MD Anderson Past
  • Collaborations
  • On Research and Researchers

Dr. Plunkett begins the story of his research on nucleoside analogues. He first mentions the collegial environment that Dr. Emil Freireich established in the Department of Developmental Therapeutics and how this encouraged basic and clinical scientists to work together, extending laboratory findings to patients.  He collaborated with Drs. Michael Keating and Freireich on pharmacokinetic profiles of leukemia treatment with various drugs (ARA-C Cytarabine was the first studied) and explains that Dr. Ken McCready helped them acquire leukemia samples.  He defines pharmacokinetics and pharmacodynamics.  (He explains Dr. Kenneth McCready’s work on intracellular metabolism and the recovery of leukemia cells.)  He then begins to talk specifically about his own work, noting his prior research in Colorado that focused on Fludarabine in B-cell malignancies.  He then explains the impact of nucleosides on DNA replication, RNA metabolism, and DNA modifications that silence gene expression.

Dr. Plunkett describes how to go about designing translational research projects and the need for researchers to know “two languages” to do this.   First the scientist must understand how cancer functions to maintain its replication capacity.  By learning the mechanism of action, the scientist is then positioned to ask what cells would be susceptible to intervention.  He gives examples of two studies that come from this kind of questioning.   He then reviews what translational research can accomplish and notes his ongoing activities with the Department of Leukemia –necessary so he can keep up his understanding of the clinical dimension of his research studies.

 

Chapter 06 (The Researcher)
Drug Studies (and How Collegiality Can Move Them Along) (listen/read)

 

Topics Covered

  • The Researcher
  • Overview
  • Definitions, Explanations, Translations
  • MD Anderson History
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • MD Anderson Culture
  • Professional Practice
  • The Professional at Work
  • Industry Partnerships
  • On Pharmaceutical Companies and Industry
  • MD Anderson Past
  • Collaborations
  • On Research and Researchers

Dr. Plunkett describes his work on Fludarabine and his discovery that it was effective on Chronic Lymphocytic Leukemia, resulting in a treatment that is now standard of care.  He explains that he first acquired Fludarabine via his professional networks (with colleagues sometimes passing packets of drug samples for study at a conference), a resource that has continued to bring him new compounds, such as Clofarabine.  Dr. Plunkett stresses how important it is to maintain collegial relationships with colleagues across institutions.  He then talks about academic institutions are doing much less drug development now than in the past.  

 

Chapter 07 (The Administrator)
Co-Director of the Leukemia Moon Shots Program (listen/read)

 

Topics Covered

  • The Researcher
  • Overview
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • MD Anderson Culture
  • Professional Practice
  • The Professional at Work
  • MD Anderson Past
  • Collaborations
  • Discovery and Success

Dr. Plunkett notes that Dr. Ronald DePinho’s has given drug development a central place in his leadership mission, bringing in a team of people devoted to this research initiative.  He explains that shares directorship of the Leukemia Moon Shots Program with Dr. Michael Keating and lists the four promising areas of research that they were unable to pursue before (because of lack of resources) and that have now been funded.  Four clinical trials of patients with chronic lymphocytic leukemia focus on Ibrunitib and its effects on a signaling pathway never before investigated.  He describes those trials and finishes this chapter with some comments on the effectiveness of fludarabine-Cytoxan-rituximab in extending leukemia patients’ lives. 

 

 

Interview Session Two: 10 April 2013 (listen/read)

 

Chapter 00B
Interview Identifier (listen/read)

 

Chapter 08 (The Researcher)
Working with Fludarabine; The Importance of Extra-Institutional Connections and Ethics (listen/read)

 

Topics Covered

  • The Researcher
  • Overview
  • Definitions, Explanations, Translations
  • MD Anderson History
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • MD Anderson Culture
  • Collaborations
  • Professional Practice
  • The Professional at Work
  • Industry Partnerships
  • On Pharmaceutical Companies and Industry
  • MD Anderson Past
  • Collaborations
  • On Research and Researchers
  • Business of Research
  • Understanding Cancer, the History of Science, Cancer Research
  • Ethics
  • Professional Values, Ethics, Purpose

Dr. Plunkett reviews the history of his work with Fludarabine and focuses specifically on how connections with colleagues at other institutions helped drive his research.  He begins by explaining how fortunate he has been to have connections with chemists and biochemists at other institutions who were very willing to provide substances for investigations to anyone who was interested.  He explains how John Montgomery provided Fludarabine, a gesture that led to a ten year investigation of its action.  Dr. Plunkett also mentions the work of MD Anderson graduate student, Peng Huang, who pursued these mechanisms and developed the knowledge base that led to combining the drug with others.

Dr. Plunkett explains that the process of acquiring drugs for study is quite different now, as pharmaceutical companies (and their legal advisors) control research very tightly.  Dr. Plunkett explains that this new system curtails imagination and the researcher’s freedom to pursue ideas in different directions.  “Pharmaceutical companies write the prescription” for studies, Dr. Plunkett notes, and this is “not the spirit of science we want anyone to be pursuing.”

Dr. Plunkett next explains the conclusions about Fludarabine that Dr. Huang established and then discusses the two investigative lines this work gave rise to.  Dr. Varsha Ghanda took up one investigative line, pairing Fludarabine with Cytarabine.  He discusses results of this study (published in 1988), referring to a graph (provided below).  Combining Fludarabine and Cytarabine (ara-CTP) was the front line work in treating certain cohorts of patients with myeloid leukemia.  A third element is now being added to the mix, Myelotarg, an antibody that creates even better results.  

Dr. Plunkett next explains the rationale for selecting patients for the Fludarabine/Cybarabine study: a cohort that was doing the best on what was available at the time.  He outlines the ethical dimensions of clinical trials.  He then summarizes his ethical values as a basic researcher: “Truth above everything,” the gold standard for reproducibility.  He next comments on his 5-year role as Research Integrity Officer, noting that many case investigated reveal honest errors.  He explains how errors can occur, noting a common discrepancy between data and the visual figures used to summarize dathe explains an imaging analysis software currently in use to locate discrepancies.

Chart - Biochemical Modulation of ara-CTP by Fludarabine

 

Chapter 09 (An Institutional Unit)
The CLL Moon Shot Program (listen/read)

 

Topics Covered

  • The Researcher
  • Overview
  • Definitions, Explanations, Translations
  • MD Anderson History
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • MD Anderson Culture
  • Collaborations
  • The Administrator
  • Professional Practice
  • The Professional at Work
  • Discovery and Success
  • Patients, Treatment, Survivors
  • MD Anderson Snapshot
  • MD Anderson Impact
  • Institutional Processes

Dr. Plunkett begins by explaining how Dr. Huang’s discoveries provided the basis for the CLL Moon Shots Program established under Dr. Ronald DePinho.  He explains that Dr.Huang’s work began with the hypothesis that the repair of DNA in a cancer cell “could be our friend” if that repair included a compound, such as Fludarabine, that would ultimately inhibit the cell’s ability to function.  He notes that this has set a standard of care for CLL and that remission rates have gone over 70%.  Next he describes how that foundational work opened up investigative areas now included in the Moon Shots Program.  Data managers have noticed that survivors of this treatment are developing secondary malignancies at a higher rate.  Investigations are now focusing on biologically based strategies, asking How does CLL arise (a pathogenesis question) and What keeps it going (a question about pathophysiology).  He describes the studies currently underway that address these questions from different perspectives. Next Dr. Plunkett explains how the CLL Moon Shot Program is structured and how the individual studies prioritized.  He notes that patients today are very aware of CLL therapies and shop for treatment armed with information they have acquired from blogs and online sources.  He explains the long and short-term aims of the CLL Moon Shots program. 

 

Chapter 10 (The Administrator)
Team Science and Training Team Scientists (listen/read)

 

Topics Covered

  • The Researcher
  • On Research and Researchers
  • Overview
  • Understanding Cancer, the History of Science, Cancer Research
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • MD Anderson Culture
  • Collaborations
  • The Administrator
  • Professional Practice
  • The Professional at Work
  • Discovery and Success
  • The Educator
  • MD Anderson Culture
  • Understanding the Institution

Dr. Plunkett begins this chapter by observing that his entire career has been based on the team science approach.  He also explains that team science is very valued (its importance underscored by the NCI) but the model of the PI on grants is still based on the independent researcher as are many parameters used in academic institutions to award promotion and tenure and even laboratory space.  (Dr. Plunkett notes that institution presidents Dr. John Mendelsohn and Dr. Ronald DePinho are both team scientists.)   Dr. Plunkett next talks about training students and young faculty for team science, noting that his laboratory is a magnet for people who want to learn “Hypothesis Testing in the Clinic,” as the Department of Experimental Therapeutics described its translational research approach.

Dr. Plunkett explains that he selects new students and faculty based on their fit with the culture of the laboratory and Department.  He also notes that the culture of collegiality and sharing can spread to other departments.  He talks about a graduate student with a degree in philosophy whom he took on trial and who ended up working as a research nurse and phlebotomist in Leukemia.

 

Chapter 11 (The Administrator)
Mentoring, Education, and Team-Science Culture (listen/read)

 

Topics Covered

  • On Mentoring
  • The Educator
  • The Administrator
  • The Mentor
  • Mentoring
  • Education
  • Portraits
  • MD Anderson Culture
  • The MD Anderson Ethos
  • Diversity at MD Anderson
  • Understanding the Institution
  • Professional Values, Ethics, Purpose
  • Institutional Mission and Values

Dr. Plunkett explains that he believes in mentoring by example as well as the importance of determining when young people are ready to absorb information about getting promoted.  He gives the example of challenges confronting fellows who wish to advance as MD Anderson faculty and speaks at length about the successes of Dr. Varsha Gandhi.  He also cites the importance of public exposure and the significance of the firm, “white knuckle handshake” that is so important in American culture.  Next he talks about the Department’s mentoring programs for young faculty, headed up by Dr. Varsha Ghandi. 

To underscore his philosophy of active mentoring, Dr. Plunkett says, “This discussion [meaning the interview] is the only time this door is closed.”  He articulates his belief that working in a laboratory is mentoring and he also notes that the Department’s Journal Clubs and research meetings offer mentoring opportunities (and this is not the case in all MD Anderson departments).  These large, collegial meetings model for trainees how “we can work together.

Dr. Plunkett comments on the career paths of physician scientists and notes that the Department does not see many medical fellows.  He then explains that his commitment to teaching comes from the desire to create a new generation of scientists.  He notes that he has stayed committed to his field because of his successes in creating end products (both knowledge and treatment).  He has oriented his laboratory toward clinically relevant questions that can be answered.

 

Chapter 12 (The Researcher)
Research with
Gemcitabine (listen/read)

 

Topics Covered

  • The Researcher
  • On Research and Researchers
  • On Pharmaceutical Companies and Industry
  • Overview
  • Definitions, Explanations, Translations
  • Multi-disciplinary Approaches
  • Collaborations
  • Understanding Cancer, the History of Science, Cancer Research

Dr. Plunkett tells the story of the contributions his laboratory made to demonstrating the efficacy of the drug Gemcitabine.  He first notes that he had many friends in pharmaceutical companies in the early 1980, among them Gerald Grindy at Eli Lily, where Gemcitabine was being developed.  He explains that he was asked to work with Gemcitabine because of its structural similarity to Cytarabine, a drug he had formerly worked on.  He recalls the speed –a few months-- with which the lab showed that Gemcitabine had metabolic effects, specifically inhibiting ribonucleotide reductase.  Paul Heinemann made the observations on the metabolic mechanisms by which Gemcitabine was retained in cells of circulating leukocytes. This became a multi-billion dollar drug for Eli Lily, approved for use in solid tumors.  Dr. Plunkett explains that a cultural/political gap between researchers and management of large corporations made it difficult for Gerald Grindy to convince Lily to keep supporting the drug.  The drugs further possibilities have not been investigated.

Dr. Plunkett then observes that the high cost of drug research often causes projects to be dropped if preliminary results do not lead in predicted direction.  He explains the importance of conducting rational tests of hypotheses and of reporting negative results.

 

Chapter 13 (The Researcher)
Exploiting Cell Death Mechanisms and DNA Repair to Kill Tumor Cells (listen/read)

 

Topics Covered

  • The Researcher
  • On Research and Researchers
  • On Pharmaceutical Companies and Industry
  • Overview
  • Definitions, Explanations, Translations
  • Multi-disciplinary Approaches
  • Collaborations
  • Understanding Cancer, the History of Science, Cancer Research
  • Discovery and Success

Dr. Plunkett tells the story of his most recent (and very gratifying work) on mechanisms of cell death (apoptosis) and Imatinib, the “poster child” of targeted therapy.  He explains that CLL cells are reliant (“addicted”) on several proteins for their survival, one of which is very short-lived so if one can block its production, all CLL cells will die.  Dr. Cortez and Kartajian demonstrated the Imatinib results.  This work also gave rise to a different strategy for CLL, one not aimed at damaging DNA, but at getting cells to kill themselves.  Dr. Plunkett next describes a project that returns to nucleoside work, based on a compound much like Cytarabine.  This story involves a Japanese scientist, Kira Matsuka, who provided Dr. Plunkett with CNDAC (2’-C-cyano-2’-deoxy-1-beta-D-arabino-pentofuranosylcytosine).  Dr. Plunkett worked on the mechanism of action independent of support while Dr. Kartajian studied the drug in acute myeloid leukemia in patients older than 70, and a multi-center phase three trial is now in progress.[1]  Dr. Liu Xiaojung in Experimental Therapeutics is conducting studies of the drug’s mechanism of action.  He has found that the drug targets a single break in the DNA strand, and was active in patients who could not repair double strand breaks.  They have identified a cohort that lacks part of a gene that leads to the inability to make double strand breaks.  The drug enables these patients to make double-strand breaks (which means they will then be able to benefit from nucleoside treatment that introduces cancer-damaging agents into DNA as it is repaired).  Dr. Plunkett confirms that this has been one of the most satisfying studies, as it brings his basic laboratory research into molecularly targeted individualized research.  He then lists other disease cohorts that might benefit from this kind of strategic approach.

 

 

Interview Session Three: 8 May 2013 (listen/read)

 

Chapter 00C
Interview Identifier (listen/read)

 

Chapter 14 (An Institutional Unit)
Developmental Therapeutics and the Origin of The Department of Experimental Therapeutics 
(listen/read)

 

Topics Covered

  • The Researcher
  • Overview
  • Definitions, Explanations, Translations
  • MD Anderson History
  • Portraits
  • MD Anderson Culture
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • Collaborations
  • Institutional Processes
  • Joining MD Anderson

To tell the story of how the Department of Experimental Therapeutics evolved, Dr. Plunkett begins with Dr. R. Lee Clark, who recognized the “two major forces in chemotherapy,” Dr. Emil Frei, III and Dr. J Freireich, who came to MD Anderson and created the Department of Developmental Therapeutics.  Dr. Plunkett explains that these two researchers were some of the first to apply combination treatments for leukemia, and their work showed the first remissions (eventually with over 80% of pediatric patients reaching long-term survivorship).  Dr. Frei left the institution in 1972, leaving Dr. Freireich to head the Department.  Dr. Plunkett emphasizes that Dr. Freireich brought together researchers from many fields who had a collaborative or a translational-research mindset: Developmental Therapeutics was a “rockin’ place,” says Dr. Plunkett, and he explains the mixture of people from different disciplines who came together.  Dr. Plunkett then describes how Dr. Freireich could handle over thirty research projects simultaneously.  He then tells an anecdote about preparing a grant proposal in two weeks, eventually being awarded funds that effectively provided his start-up funds when he arrived at MD Anderson.

Chapter 15 (Institutional Change)
Reorganizing Developmental Therapeutics: The Challenge of Naming Experimental Therapeutics (listen/read)

 

Topics Covered

  • The Researcher
  • Overview
  • Obstacles, Challenges
  • Controversy
  • MD Anderson History
  • MD Anderson Culture
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • Collaborations
  • Institutional Processes
  • Growth and/or Change
  • On Research and Researchers
  • Understanding Cancer, the History of Science, Cancer Research

Dr. Plunkett begins this chapter by explaining how MD Anderson was restructured when Dr. Charles LeMaistre replaced R. Lee Clark as president of the institution.  Under Dr. Clark, the “medical enterprise” was divided between the Division of Medicine and Developmental Therapeutics.  Dr. LeMaistre wanted to use organ sites as a principle of reorganization, so the faculty in Developmental Therapeutics were reorganized according to medical oncology principles.  Dr. Plunkett explains that Dr. Krakoff was named head of the Division of Medicine (now the Division of Cancer Medicine) and oversaw the change.  He describes what happened to the basic scientists during this process.  Dr. Plunkett joined the Department of Chemotherapy Research.  He describes how Dr. J Freireich was relieved of his administrative duties after receiving an Outstanding Investigator Award.  He then notes that with this reorganization, basic scientists didn’t have administrative representation that understood their issues and subject matter.  The situation became worse, he explains, when Dr. Bast took over from Dr. Krakoff as head of the Division of Medicine.  Dr. Plunkett goes on to explain changes in the leadership of the Division of Medicine (up to 1998)and several name changes of the department (Department of Medical Oncology, Department of Clinical Investigation), noting that there was no structure for creating collegiality among basic scientists. 

Dr. Plunkett then explains that the Department of Clinical Investigation (including the Section of Cellular and Molecular Biology) begged Dr. Bast to rename the department because the name completely misrepresented the faculty’s activities, making it difficult to secure grants.  (The Department was renamed in 1998.) 

Dr. Plunkett explains more leadership changes after 1998.  Dr. Hong became head of the Division of Medicine, which was renamed ‘the Division of Cancer Medicine,’ and the Department of Experimental Therapeutics undertook a search for a full time chair.  Dr. Plunkett notes that Bioimmunology merged with Experimental Therapeutics, and Dr. Ruben Lotan served as ad interim chair.  Dr. Plunkett then explains the reasons why Dr. Hong removed physicists from the Department eight years ago, going on to note some additional changes of leadership.

 

Chapter 16 (Building the Institution)
The Department of Experimental Therapeutics: a Strategic Plan for the Department (listen/read)

 

Topics Covered

  • The Administrator
  • The Researcher
  • Professional Practice
  • The Professional at Work
  • Collaborations
  • Leadership
  • Obstacles, Challenges
  • MD Anderson History
  • MD Anderson Culture
  • Multi-disciplinary Approaches
  • Institutional Mission and Values
  • Collaborations
  • Institutional Processes
  • Growth and/or Change

Dr. Plunkett explains that the Department of Experimental Therapeutics was located on the MD Anderson’s main campus until January of 2010, when the Department began its move to South Campus.  The increase in space is an advantage, he explains, but the new location also presents several challenges. For example, the Department uses primary materials from leukemia patients, located on North Campus, and distance and transportation have created a problem, resulting in a slowdown of research.  The Department’s faculty made many suggestions for the design of their South Campus space, but very few were followed.  Dr. Plunkett reviews the pros and cons, then explains at length how the new space presents a real challenge collaborative work, collegiality, and interaction.  Dr. Plunkett explains that, as a result, Dr. Garth Powis (Chair of the Department) had an idea to create a strategic plan to answer the question, “How do we make this a department that will represent us?”  Dr. Plunkett chaired the strategic plan committee, and he explains the initiatives they undertook as a result of the process: identifying opportunities for sharing equipment; establishing goals for mentoring junior faculty, associate professors and post-docs; creating a team-taught course on mechanisms of cancer therapeutics to give the Department more institutional exposure.  He lists activities held to increase social opportunities and collegial interaction.

 

Chapter 17 (The Administrator)
Faculty Senate and the Revised Conflict Resolution Process (listen/read)

 

Topics Covered

  • The Administrator
  • Professional Practice
  • The Professional at Work
  • Leadership
  • Obstacles, Challenges
  • MD Anderson History
  • MD Anderson Culture
  • Institutional Processes

Dr. Plunkett talks about his administrative roles within the institution, touching briefly on his role as Director of Research for Experimental Therapeutics (2005-2008), then discussing his role in revising the grievance process for the faculty.  He explains that the Faculty Senate identified the problem: a lack of defined pathways for grievance, and this led to Dr. John Mendelsohn creating “The Blue Ribbon Panel for Peer Review and Conflict Resolution,” a 12-15 person panel.  He explains the problems with the existing grievance process, then lists the three options the panel set in place to create a rational set of steps to resolve conflict.  1) Conferring with the Ombudsman, 2) Working with a professional mediator, 3) Presenting conflict to a faculty panel.  Dr. Plunkett talks about the main sources of conflict for the faculty.

 

Chapter 18 (Overview)  
Conflict of Interest: MD Anderson Faculty and Presidents (listen/read)

 

Topics Covered

  • The Administrator
  • Professional Practice
  • The Professional at Work
  • Leadership
  • Obstacles, Challenges
  • MD Anderson History
  • MD Anderson Culture
  • Institutional Processes
  • Ethics
  • On Ethics

Dr. Plunkett explains that in the nineties, conflict of interest became such a prevalent issue at the institution that a Conflict of Interest Committee was convened (in 1996) with president Dr. John Mendelsohn’s backing.  After Dr. Stephen Tomasovic stepped down as the first committee chair, Dr. Plunkett took on that role.  At the time, conflict of interest was dealt with by “collegial agreement” involving no legal assistance.  The Committee wrote a formal policy that was adopted.  Dr. Plunkett explains the conflict of interest issues arising because of John Mendelsohn’s role in developing the drug Cetuximab (as well as the concurrent problems arising because he was involved with Enron.)  Dr. Plunkett describes the impact of the conflict of interest policy.  He describes how conflict of interest can arise for clinical faculty in an environment where pharmaceutical companies “had been overtly attempting to buy physicians.”  Conflict of interest can arise sometimes for translational researchers, he explains, but doesn’t really affect basic scientists.  Dr. Plunkett then talks about the restrictions in place to prevent conflict of interest then extends the discussion to the current president, Dr. Ronald DePinho.  He notes that MD Anderson was ahead of other institutions in creating formal policies to address conflicts of interest.

 

Chapter 19 (The Administrator)
Research Integrity Officer (listen/read)

 

Topics Covered

  • The Administrator
  • Ethics
  • On Ethics
  • Overview
  • Definitions, Explanations, Translations
  • Building/Transforming the Institution
  • On Research and Researchers
  • On Leadership
  • On Mentoring
  • Professional Practice
  • The Professional at Work
  • Leadership
  • Obstacles, Challenges
  • MD Anderson History
  • MD Anderson Culture
  • Institutional Processes
  • Personal Reflections on MD Anderson         
  • Giving Recognition
  • Professional Values, Ethics, Purpose

Dr. Plunkett explains how he assumed the role of Research Integrity Officer and describes his responsibility to address allegations of research falsification, fabrication, or plagiarism.  He explains that the Office of Research Integrity was created by an unfunded mandate from the NIH and the Department of Public Health: the Office of Research Integrity answers to these government bodies via the Provost.  Dr. Plunkett explains that suspicions about infraction are brought to the Office’s attention confidentially and usually by an anonymous complainant.  He explains the three-phase process used to address the allegations: evaluation, inquiry via a panel, and formal intervention.  Eight cases were investigated in 2012.  Dr. Plunkett distinguishes between research integrity issues and research ethics issues that are referred to the Ombudsman or the Provost.  In general, he says, people are sloppy and what looks like research misconduct generally comes about through careless errors made while acquiring and handling data.  Dr. Plunkett explains that researchers who have been subjected to scrutiny by the Office of Research Integrity often spur their colleagues to be more careful.  He also describes an ad hoc, virtual community of data analysts, who scrutinize data made public for errors.

Dr. Plunkett expresses how honored he feels to have the confidence of the Faculty and to have been asked to serve the role of Research Integrity Officer.  He notes the bond that grows between individuals who serve on panels or committees that deal with integrity issues.

 

Chapter 20 (The Researcher)
Skills and Support for New Research (listen/read)

 

Topics Covered

  • Character, Values, Beliefs, Talents
  • Overview
  • Definitions, Explanations, Translations
  • The Researcher
  • Patients
  • Professional Practice
  • The Professional at Work

Dr. Plunkett observes that he is not often required to develop new skill sets, as he does not work in the lab anymore.  He more often develops new ideas and exercises his skills of data interpretation.  He then observes that the MD Anderson Core Facility offers basic services to researchers at the institution and serves as a pool of laboratory skills.  He notes that Dr. Ronald DePinho is head of a grant that includes many Cores and Programs, and that received a rating of “exceptional” from the review committee.

 

Chapter 21 (Key MD Anderson Figures)
MD Anderson Presidents (listen/read)

 

Topics Covered

  • Portraits
  • MD Anderson History
  • MD Anderson Culture
  • Professional Practice
  • The Professional at Work
  • Influences from People and Life Experiences
  • Understanding the Institution
  • Growth and/or Change
  • Controversy

In this chapter, Dr. Plunkett sketches his view of the MD Anderson presidents, noting that Dr. Charles LeMaistre [Oral History Interview] was separated from the Faculty by a “layer of VPs.”  Dr. John Mendelsohn [Oral History Interview], in contrast, was responsive to the Faculty: his was part of the Department of Experimental Therapeutics and lectured in the Department’s lead course.  Dr. Plunkett says that Dr. Ronald DePinho has been outgoing with his Town Halls.  Dr. DePinho’s Moon Shots have brought together diverse groups of people.  Dr. Plunkett says he expects that the difficulties with Dr. DePinho’s leadership will smooth out.

 

Chapter 22 (View on Career and Accomplishments)
J Freireich’s Impact and A Career Commitment to Collaborative Work (listen/read)

 

Topics Covered

  • Portraits
  • MD Anderson History
  • Multi-disciplinary Approaches
  • Overview
  • Definitions, Explanations, Translations
  • The Researcher
  • MD Anderson Impact
  • This is MD Anderson
  • Discovery and Success
  • Multi-disciplinary Approaches

Dr. Plunkett begins this chapter with womments about contributions made by J Freireich.  He notes that Dr. Freireich made his own work possible: his work opened a new era in studying leukemia cells and that some of the most exciting work is still based on his pioneering advances.  As an example, Dr. Plunkett talks about the efforts to determine the mechanisms that create a specific genetic lesion’s drug sensitivity.  He notes that work on cellular pharmacology enabled him to interact with clinical colleagues and trainees, collaborations that increased cross-department trust and established Dr. Plunkett’s lab as the “go-to” resource for questions about specific compounds.  He explains that the laboratory continues to generate hypotheses and study the susceptibility of cancer cells. He describes how blocking protein synthesis can lead to tumor-cell death, leading in turn to tumor lysis syndrome, where the body responds to the rapid death of a tumor.

Looking back at the path of his career, Dr. Plunkett says he is particularly thankful to have trained in the basic sciences and then progress to clinical applications.  He notes that MD Anderson gave him the luxury of extending his work to clinical investigations and being recognized for his contributions.  Once again, he credits Dr. J Freireich for bringing different specialties together in collaborative situations.  At the end of the interview he speaks about Dr. Michael Keating’s role in building philanthropic support, “the glue for national and international collaboration.” 


[1]Dr. Plunkett expands on a related drug produced by Cycacel, a company mentioned in the interview session:

 

“The compound that Cyclacel has in clinical trial is an orally-available pro-drug called sapacitabine.  We don’t use it in the lab because it requires metabolism to generate the parent nucleoside, CNDAC.  This, by the way, is also in clinical trial at MDACC in acute leukemias (Kantarjian).  It is administered parenterally (intravenous), and provides some flexibility in dosing compared to sapacitabine. Further, Sankyo made the pro-drug sapacitabine from CNDAC.  The clinical results were first reported in phase 1 clinical trials, the purpose of which is to determine safety, although we always look for clinical activity.  These were in solid tumors (lung, colon breast, etc.) of patients who had failed many prior therapies  These were conducted mostly by Sankyo Pharmaceuticals, who later dropped the compound (then known as CS-682).  After Cyclacel licensed the drug from Sankyo and re-named it sapacitabine, Dr. Kantarjian tested sapacitabine in acute myeloid leukemia in a phase 1 trial;  there were responses, including complete remissions.  This progressed to a phase 2 trial, and some combination trials before the current phase 3 trial was designed and initiated.”  (From Email correspondence, 12 April 2013).


Original Profile

Dr. William Plunkett, Ph.D. (b. Boston, 4 May 1943), Deputy Chair of the Department of Experimental Therapeutics, is interviewed over three sessions (approximately 6 hours 31 minutes).  Dr. Plunkett came to MD Anderson in 1975 as an Assistant Biochemist in the Department of Developmental Therapeutics and joined the faculty of that Department as an Assistant Professor later that year.  He now holds the Barnts Family Distinguished Chair for Cancer Research as well as a joint appointment in the Department of Leukemia.  The interview sessions take place in Dr. Plunkett’s office on the South Campus of MD Anderson.  Tacey A. Rosolowski, Ph.D. is the interviewer.

Dr. Plunkett received his B.S. in Biology and Chemistry from Springfield College, Springfield, MA (1965) and his Ph.D. in Biochemistry from the University of Massachusetts, Amherst (1970).  He went on to a Research Fellowship in Physiology at the Marine Biological Laboratory, Woods Hole, Massachusetts (6/1967−9/1967), a Postdoctoral Fellowship in Therapeutic Research at the University of Pennsylvania in Philadelphia (1970−1971), and then took a position as a Research Associate in Microbiology at the University of Colorado Medical Center, Denver (1972−1975).  Since coming to MD Anderson, Dr. Plunkett’s work has focused on the study of the cellular mechanisms that control tumor viability, using this knowledge to develop innovative strategies to kill tumor cells.  From 1993−2004 he served as Chief of the Section of Cellular & Molecular Pharmacology, Department of Experimental Therapeutics, then as the Department’s Director of Research Development from 2005−2008, prior to his role as Deputy Chair.

Dr. Plunkett has been elected the chairman of the Gordon Research Conference on Purines & Pyrimidines, and as President of the Graduate Faculty of the University of Texas Graduate School of Biomedical Sciences.  He is the recipient of the Service to Mankind Award from the Leukemia Society of America, the Faculty Achievement Award for Clinical Research from M. D. Anderson Cancer Center, and the 1st Sowell-Huggins Professorship in Cancer Research from the University of Texas Graduate School of Biomedical Sciences. 

In this interview, Dr. Plunkett goes into detail about the evolution of his investigations into the cell mechanisms of tumors.  He begins with his work on the nucleoside analogues fludarabine and gemcitabine, which are taken up into tumors cells, then interfere with their DNA synthesis, eventually killing those cells. He also discusses his recent work on apoptosis, the intrinsic mechanisms by which a tumor cell programs its own death.[1]  His discussion of research reveals his own attitudes toward collaborative work: Dr. Plunkett frequently notes that collaboration and collegiality can advance scientific work.  Dr. Plunkett is also a keen observer of institutional change he explains the processes by which divisions and departments have been reorganized and changed under different leadership.  Dr. Plunkett also explains his recent role as MD Anderson’s Institutional Research Integrity Officer (and comments on ethical issues within the institution).  Also explains his role as co-director of the Moon Shot Program devoted to Chronic Lymphocytic Leukemia under Dr. Ronald DePinho.


[1] The multi-disciplinary (and translational) nature of Dr. Plunkett’s work (as well as periodic institutional restructuring) resulted in his connection with a number of different departments: Developmental Therapeutics, Chemotherapy Research, Medical Oncology, Clinical Investigation, Experimental Therapeutics, and Leukemia.