Two interview sessions: 8 August 2012, 10 August 2012
Total approximate duration: 3 hours 20 minutes
Interviewer: Tacey A. Rosolowski, Ph.D.
About the Interview Subject:
Louise Connally Strong (b. 1944, San Antonio, Texas) came to MD Anderson in 1972 as a Research Associate in the Graduate School of Biomedical Sciences. She is a full professor and Chief of the Section of Clinical Cancer Genetics in the Department of Genetics with joint positions in the Graduate School of Biomedical Sciences, in MD Anderson’s Department of Pediatrics/Biology and in Cancer Genetics in Breast Medical Oncology.
Dr. Strong has conducted longitudinal studies of inherited genetics patterns of neuroblastoma, aniridia, and Wilm’s tumor. She is best known for her her discovery of the p53 tumor suppressor genes and its link to Li-Fraumeni syndrome.
She has served ad interim Co-Director for Human Cancer Genetics Program Clinical Cancer Genetics, as Deputy Department Chair, Department of Experimental Pediatrics in the Division of Pediatrics, and as Director for Basic Research, Division of Pediatrics. Outside the institution, she served on NCI Data Evaluation Human Risk Assessment Project and President of American Association for Cancer Research (’96 – ’97). She was appointed by President Ronald Reagan to two terms on National Cancer Advisory Board.
Major Topics Covered:
Personal and educational background
Overview and history of oncology genetics in the sixties and seventies
Working with Alfred Knudson
Research: longitudinal studies of inherited genetics patterns of neuroblastoma, aniridia, and Wilm’s tumor; discovery of the p53 tumor suppressor genes and link to Li-Fraumeni syndrome, survivorship
Women at MD Anderson
MD Anderson’s cancer screening program
Ethics and genetic testing
MD Anderson growth and cultural change
Interview Session One: 8 August 2012
Genetics and Cancer in the Sixties and Seventies
Chapter 01 / Overview
A Lucky Introduction to MD Anderson and Alfred Knudson
Chapter 02 / Educational Path
An Unusual Route to Medical School
Chapter 03 / Educational Path
A Post-Doctoral Project on Childhood Cancer; Working with Alfred Knudson
Chapter 04 / The Researcher
Discovering Contiguous Genes that Control Aniridia and Wilm’s Tumor
Chapter 05 / The Researcher
The Discovery of the p53 Tumor Suppressor Gene
Chapter 06 / The Researcher
The Next Phase of the p53 Tumor Suppressor Gene Story
Chapter 07 / The Researcher
Interview Session Two: 10 August 2012
Creating a Cancer Screening Program
Chapter 08 / Building the Institution
An Ongoing Survivorship Study and Related Research
Chapter 09 / The Researcher
Establishing a Clinical Cancer Genetics Program
Chapter 10 / The Administrator
A Philosophy of Genetic Information and Its Integration into MD Anderson
Chapter 11 / Overview
The First Woman Faculty Member with an Endowed Chair
Chapter 12 / Diversity Issues
Growth and MD Anderson Presidents
Chapter 13 / Institutional Change
Interview Session One: 8 August 2012 (listen/read)
Interview Identifier (listen/read)
Chapter 01 (Overview)
Genetics and Cancer in the Sixties and Seventies (listen/read)
In this Chapter Dr. Strong sketches the first links that researchers made between cancer and genetics in the 1960s and ‘70s. Examination of chromosomal abnormalities in leukemia cells made it clear that cancer was connected to genetics, and research was being done on hereditary factors controlling retinoblastomas in infants. However, since most cancers do not follow an inherited pattern, she explains, most people were not examining the link, focusing instead on viruses and environmental factors. In medical school, her interest in inheritance and cancer made her unusual, as did the fact that she wanted to do research rather than practice medicine.
Chapter 02 (Educational Path)
A Lucky Introduction to MD Anderson and Alfred Knudson (listen/read)
In this segment, Strong describes how working on MD Anderson’s pediatric ward during her medical school residency helped convince her to focus on childhood cancer. An even stronger factor was her period of post-doctoral study with MD Anderson geneticist, Alfred Knudson, MD, PhD, who was working on a genetic model for retinoblastoma. Dr. Strong explains the sheer luck of coming into Dr. Knudson’s office and discovering that he shared her interest in inherited factors and could offer her a role on his research project. She also explains some of the characteristics of cancer as a disease that offered specific intellectual challenges.
Chapter 03 (Educational Path)
An Unusual Route to Medical School (listen/read)
Dr. Strong begins this Chapter by talking about her deep roots in Texas and Houston. (She is the only one in her family not born in Houston.) She also notes that her mother’s family was in the sciences (her mother’s father was a pediatrician); her father’s family was in law. She excelled in the sciences in high school and majored in both mathematics and biology at the University of Texas-Austin, aiming toward a graduate program in genetics research. (She had been accepted at Stanford University.) She explains why she ended up going to the University of Texas Medical Branch in Galveston, Texas. She also talks about the isolation that she felt in medical school, as one of the only 5% of women in the program, and describes how she combated this by taking every opportunity to study in Houston. This is how she became connected to MD Anderson. She ends this Chapter with comments on the advances in medical technology (gene sequencing, for example, and the alteration of genes) that have enabled advancements in genetics that she never imagined would take place in her lifetime.
Chapter 04 (The Researcher)
A Post-Doctoral Project on Childhood Cancer; Working with Alfred Knudson (listen/read)
In this segment, Dr. Strong goes into great detail about her work with Dr. Alfred Knudson during her post-doctoral fellowship. Dr. Knudson had been working on a “two-hit model of retinoblastoma.” Dr. Strong first explains the scope of this study, clarifying that the “two hits” refers to the number of genetic mutations that lead to vastly increased chance for multiple cancers. She explains the hypothesis and rationale of Dr. Knudson’s study: he wanted to identify a scenario where a minimal number of factors and numbers of chromosomal changes would result in cancer. This study revealed that children with retinoblastoma had a mutation in which genetic material was deleted, and Dr. Strong points out that this approach and the outcomes set the stage for the discovery of tumor suppressor genes. She then goes on to describe how her post-doctoral project generalized Dr. Knudson’s model to other cancers. She reviewed records of MD Anderson patients and looked for individuals who had been treated for retinoblastoma and who returned years later with cancer in other organs –neuroblastoma and Wilm’s tumor (of the kidney), for example. At the end of this segment, Dr. Strong offers a very personal portrait of Dr. Knudson, who mentored her and taught her to question doctrine, to think from an analytical perspective, and also to not take herself too seriously.
Chapter 05 (The Researcher)
Discovering Contiguous Genes that Control Aniridia and Wilm’s Tumor (listen/read)
At the beginning of this segment, Dr. Strong explains that she became a part time faculty member and had her children after her post-doctoral study. She realized, however, that she “would go nowhere” on part time status and joined the full time faculty with a position in the Medical Genetics Center in 1976. She then describes how she focused her research interests on childhood cancer and genetic epidemiology: she would look at individuals who had had retinoblastoma as tiny babies, who had been irradiated as part of therapy, and who had additional cancers, working with the assumption that this risk came from genetic predisposition. She explains two hypotheses that did not yield results, then explains how she discovered that aniridia (the absence of an iris in the eye) and Wilm’s tumor (of the kidney) are controlled by contiguous genes. She could now go to patients, she explains, and give them information about their risks for developing Wilm’s tumor or passing the predisposition to the next generation.
Chapter 06 (The Researcher)
The Discovery of the p53 Tumor Suppressor Gene (listen/read)
In this segment, Dr. Strong talks about a study that began in the 70s and has still not endethe study of Li-Fraumeni syndrome. She explains the syndrome, first noting that Li and Fraumeni were unusual epidemiologists who were interested in “outlier, unusual events” that might, nonetheless be significant. They discovered families with many individuals who had multiple cancers and published a paper in 1969 proposing that this was a familial, and thus genetically linked, syndrome. Dr. Strong set up her own study in the 1970s, and she explains that she looked at MD Anderson patients treated for childhood soft tissue tumors between 1944 and the early 1970s, who had survived at least five years. Such a study could not be done today, she explains, given privacy laws. However, at the time, she located the families to take a history, look at risks for second cancers, and do cytogenetic studies. Of those she could locate, a surprising 96% of patients/families agreed to participate in the study, a testament, Dr. Strong believes, to the care they had received at MD Anderson and their commitment to help fight childhood cancer. Her study revealed that 5-10% of cancers came from inheritance, which fit the Li-Fraumeni model. At the time, she attended a talk at Cold Spring Harbor and heard that gene p53 seemed to be a tumor suppressor gene, and she became convinced that the Li-Fraumeni Syndrome was linked to this gene.
Dr. Strong then tells a story of how a technician, leaving some cultures of fibroblasts while on vacation, accidentally provided proof that normal fibroblasts were transformed by oncogenesis and became “immortalized” (i.e. they didn’t die when expected). This would have helped support the theory of the suppressor gene’s role in Li-Fraumeni Syndrome, but Dr. Strong explains that they could not get the results published because no one believed it –no one except Dr. Stephen Friend in Boston, who became a project collaborator. Dr. Strong recalls the moment when Dr. Friend sequenced the p53 gene and identified the acquired and inherited elements that would create a tumor. They were so excited and all went to Boston to write the paper (published in Science in 1990). Dr. Strong is also very moved by the memory of the knowledge she felt she suddenly had about individuals and their terrible risk of getting cancer. She then sketches the next steps taken to test samples from 25 families at MD Anderson, working with others in the Department of Genetics.
Chapter 07 (The Researcher)
The Next Phase of the p53 Tumor Suppressor Gene Story (listen/read)
Dr. Strong begins this Chapter by noting that though she is a specialist in the genetic epidemiology, she did not really “fit in Genetics” at MD Anderson because the Department had no human genetics program. (She mentions her joint appointments Pediatrics and Department of Breast Medical Oncology.) She describes how she has brought together teams of people who would never have worked together otherwise and also mentions her ability to get grants and to keep them going for long periods of time, finding new collaborators as others retire or leave. She notes her skills in creating groups that share resources and responsibilities.
Next, Dr. Strong explains that even though the discovery of the role of gene p53 in Li-Fraumeni Syndrome was established over ten years ago, the story is not over. She and her collaborators are currently studying over 100 families who show the mutation, and another 175 families that have a phenotype profile of the syndrome without exhibiting alterations of the gene. She is also very committed to putting together a team that will bring cancer screening for Li-Fraumeni Syndrome to MD Anderson using a rapid whole-body MRIs and other techniques. She cites project in Canada and in Utah where this screening has been done, with dramatic impact on survival rates. She has interest from clinicians in MRI and Imaging. Money stands in the way, and she describes the difficulties in funding a project of this kind. Dr. Strong explains that MD Anderson should be taking a leadership role in this screening, since it involves other areas in which MD Anderson is well known: development of imaging technology, sarcoma treatment, and chemoprevention, for example. She also notes the research and treatment benefits: if it can be shown that this kid of screen works with a high risk group, it will work for those in lower risk groups a well. (Dr. Strong continues with this topic in Chapter 8.)
Interview Session Two: 10 August 2012 (listen/read)
Interview Identifier (listen/read)
Chapter 08 (Building the Institution)
Creating a Cancer Screening Program (listen/read)
In a follow up to Chapter 7, Dr. Strong goes into greater detail about plans to create a Screening Program for Li-Fraumeni patients at MD Anderson. She explains that in the past, screening programs were not established because there was little that clinics could offer patients if cancers or predispositions were discovered. (She also explains the international consensus that children should not be screened.) One year ago, however, results of a small screening study in Canada was published, reporting that everyone who had not been screened had died and everyone who had been screened lived. Dr. Strong then discusses the issues to be considered when setting up a screening program: Should this be a clinical trial? Should it be randomized? Screening programs for Li-Fraumeni patients are expensive, involving rapid whole body MRIs, brain MRIs, breast MRIs, blood studies and other procedures every three to four months over the patient’s life. Screening programs are already underway in the U.S. (in Utah, at the University of Michigan, and at the NCI). There has been good response from insurance companies. Dr. Strong notes that MD Anderson could offer MRI technology that is more refined than what is currently being used. She adds that it’s key that MD Anderson offer the best clinical options for patients and reduce the expenses associate with cancer causing therapies. For Dr. Strong, this is the most important project for her to implement in the next year.
Dr. Strong explains that money is always the biggest obstacle to setting up such a program and notes that rapid whole body MRI has no CPT code for insurance purposes. She describes what is involved in educating an insurance company about the medical necessity of a procedure. She also explains why a program as intensive as the Canadian screening program may be difficult to maintain. She explains why she believes that a study supported by inter-institutional collaboration would be cost effective and produce more research results. Right now MD Anderson has a consortium of potential collaborators in Utah, at the University of Michigan, the Dana-Farber Institute, City of Hope, and several other institutions.
Chapter 09 (The Researcher)
An Ongoing Survivorship Study and Related Research (listen/read)
Dr. Strong’s Mutational Model for Childhood Cancer is a study of survivorship ongoing since the 1970s. Dr. Strong first explains this study’s relationship to her first work, with Dr. Alfred G. Knudson (at MD Anderson), on the “two-hit” model for cancer predisposition. She has incorporated the perspective that any existing genetic mutations creating a cancer predisposition will also be influenced by “mutogenic events,” such as chemotherapy and radiation therapy, as well as environmental factors such as cigarette smoking and UV exposure.
Dr. Strong explains that this research evolved along with the increasing numbers of survivors of childhood cancer since the 70s who went on to have children with increased risk. Her studies follow all families of survivors of Wilm’s tumor, and brain and bone sarcoma.
Dr. Strong goes on to note that she has participated since the mid 1990s in a large study of cancer survivorship (20,000 patients involved). The studies involve detailed examination of the treatments these patients received as well as tracking of subsequent cancers. She notes that the study will be starting a new cohort, as the treatments the original cohort received are not necessarily used today. These studies are very expensive, she notes, and funding may run out. She explains the funding supporting her Mutational Model studies via NIH RO1 grants. She also notes that this is a unique study: there are not a great many people studying genetics and childhood cancer. Nevertheless, she states that the NCI has recognized this study as unique and is funding it for the next five years. Survivorship studies are not in direct competition for funds with “moonshot” initiatives and drug therapy studies. The NCI has set aside money for survivorship studies and recognized them as a priority, and institutions tend to follow the NCI’s lead.
Chapter 10 (The Administrator)
Establishing a Clinical Cancer Genetics Program (listen/read)
In this segment, Dr. Strong explain that, since her discovery of the role of the p53 gene in creating cancer risk, Dr. Strong has advocated that MD Anderson set up a genetic counseling service and support. The desire to have a clinical genetics program predated the discovery of BRCA, and Dr. Strong explains this history near the end of this segment. She begins, however, with a discussion of how the process unfolded after 1994, when the discovery of the “breast cancer gene,” BRCA, hit the media, raised many medical and social issues, and spurred women to demand genetic testing and counseling. Cancer centers all over the country had to address these issues and, though MD Anderson had many candidates for testing, Dr. Strong says that the institution was not a leader in setting up a genetic program. Eventually the administration responded to patient pressure to provide clinical genetic services. Dr. Strong lists others who agreed that genetic counseling and testing should be provideGordon Mill, Susan Peterson, Chris Amos, among others. They would gather informally at Baylor to discuss how to handle cases, as the medical and ethical issues raised were so new. After conversations with Robert Bast, Head of the Division of Cancer Medicine, and Frederick Becker, Vice President for Research, MD Anderson hired one genetic counselor. Dr. Strong describes how the program changed over the years, as more counselors were added to a central location, and then were decentralized, and attached to Departments where they could be effective members of teams. Dr. Strong describes the strengths and weaknesses of the programs, how unaware many researchers and clinicians are about genetic issues, and how she would like this program to grow in the next years.
Here Dr. Strong describes how the decentralized Clinical Cancer Genetics Program operate. It has nine genetic counselors and offers conferences for patient education. Dr. Strong notes that the leadership is not looking at how to reorganize the program, in which most dealings with patients are handled face-to-face. They hope to offer more education through video and satellite offering. She describes the time-intensive process of working with patients to identify their risk levels and talks about an exciting development in the fall, when the Cancer Genetics Program will link with PreCare [confirm name of this program] software to be tested in some MD Anderson departments. This program allows a patient to complete their background information prior to coming in. Dr. Strong explains the feasibility of creating algorithms to identify patients who should be referred for genetic counseling. Dr. Strong explains that she set up the information systems for her own research, and Cancer Genetics set up their own network that can draw pedigrees and do analyses of them. This is the system that will be linked to PRECARE.
Chapter 11 (Overview)
A Philosophy of Genetic Information and Its Integration into MD Anderson (listen/read)
In this segment, Dr. Strong discusses several issues that emerge as genetic information is available to patients and to institutions. Though individuals still believe that “they are their genetic information,” Dr. Strong believes that eventually genetic information will be less stigmatizing and regarded as equivalent to other kinds of medical information. She believes this will take some time, but surveys show that most individuals respond positively when asked to join gene sequencing studies. They want their information to be shared, which she sees as a positive sign. In the medical community, she explains that there are still gaps between genetics and departments that are unaware of the importance of genetic information. She explains that there is a generational factor –how much genetics one had as part of medical training, and how much contact a clinician or researcher has to a geneticist as part of a team.
Chapter 12 (Diversity Issues)
The First Woman Faculty Member with an Endowed Chair (listen/read)
Dr. Strong explains the factors that led her to become the first female faculty member at MD Anderson with an endowed chair (1981), eventually named the Sue and Radcliffe Killam Chair. She explains that ideas of genetics in cancer were new. She also traces the roles she played on the national stage, adding to her reputation. In 1975, when she was asked to give a talk at the National Cancer Advisory Group and then invited to be part of the NCI Data Evaluation Human Risk Assessment Project (’76 – ’80), she took on responsibility for preparing reports on the dangers of toxins. She then was on the Board for Epidemiology, part of the Board of Scientific Counselors, then on served on the National Cancer Advisory Board. She also notes that the Killams, who endowed the chair, were family friends, though she explains that she does not know if they were aware how their funds were being directed.
Chapter 13 (Institutional Change)
Growth and MD Anderson Presidents (listen/read)
Dr. Strong first comments briefly on how lucky Texans are that a few visionaries purchased some swampland and built a cancer center that is a huge benefit to Texas and known all over the world. She also briefly notes that her grandfather was the first pediatrician in Texas, when pediatrics was a very new specialty. She then lists several downsides of MD Anderson’s growth and restructuring as a corporation. She notes the expansion of administration, a non-money making sector of the institution, though she notes that the attitudes toward patients continues to be outstanding. She would like to see better communication between the administration and faculty, and tags hierarchies as the main impediment to any free flow.
Dr. Strong recalls Dr. R. Lee Clark’s fast decision-making, his loyalty, and his focus on patient care and innovative therapies such as radiation. She did not interact extensively with Dr. Charles LeMaistre, but recalls with concern a period in the 80s and 90s when she believed patient care was not a good as it might have been due to financial difficulties the institution faced. She notes that situation changed completely when Dr. John Mendelsohn assumed the presidency and established more effective processes for patient care. She recalls he was very hands on in recruitment, but with time became more isolated. She sees Dr. Ronald DePinho as a strong basic scientist anxious to raise MD Anderson’s reputation in this area, but she expresses concern about how quickly he seems to expect the culture of MD Anderson to change. She also feels he may not be attending to the needs of clinicians, who have had no respite since 2008, when they were expected to increase their patient loads to contribute more financially to the institution. At the end of this segment, Dr. Strong explains that Dr. DePinho’s work developing drugs that target the genetic makeup of tumors intervenes differently in the progress of cancer than her own genetic studies.
This two-session interview was conducted with Dr. Louise Connally Strong (b. 1944, San Antonio, Texas) in August of 2012 for a total of approximately 3 hours and 20 minutes. Dr. Strong came to MD Anderson in 1972 as a Research Associate in the Graduate School of Biomedical Sciences. She became a full-time assistant professor in 1976. Today she is a full professor and Chief of the Section of Clinical Cancer Genetics in the Department of Genetics at MD Anderson. She holds the Sue and Radcliffe Killam Chair, the first endowed chair created for a woman faculty member (in ’81). Dr. Strong is best known for her discovery that a defective form of the p53 gene can be inherited and create a risk for many different cancers. The interviews take place in a conference room in the Department of Genetics in the Main Building of MD Anderson’s main campus. Tacey A. Rosolowski, Ph.D. is the interviewer.
Dr. Strong received her Bachelor of Arts in Mathematics in 1966 from the University of Texas at Austin and went on to earn her M.D. from the University of Texas Medical Branch in Galveston in 1970. From 1970 to 1972 she held a post-doctoral Fellowship at the Texas Research Institute of Mental Sciences and the UT Graduate School of Biomedical Sciences, working with Dr. Alfred Knudson. She then came to MD Anderson for a position as a research associate in the Graduate School of Biomedical Sciences in 1972-’73, then held a position as a part time assistant professor in Pediatrics and Biology from 1973 to 1975. She advanced to full-time status the following year. She holds joint positions in the Graduate School of Biomedical Sciences, in MD Anderson’s Department of Pediatrics/Biology and in Cancer Genetics in Breast Medical Oncology, In the Biological Sciences in the UT School of Public Health.
Dr. Strong has served ad interim Co-Director for Human Cancer Genetics Program Clinical Cancer Genetics, as Deputy Dept Chair, Dept of Experimental Pediatrics in the Division of Pediatrics, and as Director for Basic Research, Division of Pediatrics. Outside the institution, she served on NCI Data Evaluation Human Risk Assessment Project and President of American Association for Cancer Research (’96 – ’97). She was appointed by President Ronald Reagan to two terms on National Cancer Advisory Board. Among her awards are the Outstanding Faculty Award from the Graduate School of Biomedical Sciences (1994) and the Chalres A. LeMaistre Outstanding Achievement Award in Cancer (1999).
In this interview, Dr. Strong provides an overview of her research into cancer genetics in the context of that field. She speaks about her close working relationship with Dr. Alfred Knudson (Interview #34), whose “two-hit” genetic model for retinoblastoma (1971) revolutionized thinking about genetic predispositions to cancer. She speaks at length about her longitudinal studies of inherited genetics patterns of neuroblastoma, aniridia, and Wilm’s tumor, leading to the discovery of the p53 tumor suppressor genes and its link to Li-Fraumeni syndrome in the early 1990s. She discusses the ethical issues raised by genetic testing, as well as the need for genetic counseling and support, new information processing systems, and greater awareness in all departments of the importance of genetic information. Dr. Strong also discusses the challenges she faced as a woman faculty member. She offers her observations on how MD Anderson’s rapid and dramatic growth has altered institutional culture.