Dr. Elizabeth Stern
Medical School Graduation 1939

In a recent issue of Scientific American, Dr. Elizabeth Stern was identified as “probably one of the most significant physician-scientists who worked at the interface of epidemiology and cancer in the mid-20th century … her groundbreaking research led the way to our modern understanding of the prevention, diagnosis and treatment of cervical cancer.” 1

Dr. Elizabeth Stern (1915-1980) was an important contributor to the fields of cytopathology and epidemiology, two emerging fields of research toward the mid- twentieth century.

• Cytopathology refers to the diagnosis or detection of disease at the cellular level, such as through the use of tissue biopsies or analyzing individual cells. These studies can be used to determine the stage of disease, assign appropriate treatment, and monitor patient progress over time.

• Epidemiology is the study of disease distribution within and across populations to discover patterns related to socioeconomic status, age, sex, geographic location, and other factors. The results of epidemiological research help guide public health policy.

Dr. Stern was a careful, thorough and meticulous observer applying techniques from both cytopathology and epidemiology, publishing over 45 papers. She developed cytological criteria that enabled detection of early-stage cervical cancer, allowing earlier treatments and reducing patient deaths.

Dr. Stern’s research defined the earliest stage of cervical cancer development, known as cervical dysplasia2, and demonstrated the systematic progression of cells from this stage to invasive cancer [1]. Although not widely recognized at the time, dysplasia is now a conventional pre-cervical cancer indicator, and patients with cervical dysplasia are closely monitored for signs of progression to cancer.

Dr. Stern’s work on cervical cancer and dysplasia is tied to her studies on birth control pills. Original forms of birth control pills contained 10 to 100 times more estrogen than safe, leading to harmful side effects largely neglected by the medical profession at that time. Dr. Stern found that high-dose birth control pills were linked to increased risk of dysplasia and cervical cancer [2]. This finding coincided with the growing consumer advocacy movement regarding birth control pills and together these led to reformulation of pills with lower and safer estrogen levels.

In terms of cancer epidemiology, Dr. Stern was well aware that rates of cervical cancer were substantially higher in poor as opposed to middle- and upper-income neighborhoods. She worked closely with public health researchers to establish guidelines for successful community cervical cancer screening clinics in underserved areas. Many of her suggestions such as offering childcare and/or transportation remain relevant today. Her focus on empathy and clear communication were years ahead of her time [3-5].

Dr. Stern also worked on improving the Pap test . Her research with the Jet Propulsion Laboratory streamlined the processing of cervical tissue samples, leading to faster and more accurate diagnoses using digital, automated analysis of Pap tests [6-8]. Dr. Stern’s contributions were essential to the current version of the Pap test used today in hospitals, clinics and cytopathology labs around the world, and have had a major role in reducing cervical cancer rates in the United States and abroad.

Early Life and Education

Elizabeth Stern was born in Cobalt, Ontario, Canada, the fifth of eight children, to parents George and Sarah Stern. George Stern (1883-1948) was from the Pale of Settlement in western Imperial Russia, an area officially designated for Jews and beyond which Jewish residency, permanent or temporary, was generally prohibited. Sarah Morgenstern (1883-1964) was from Lodz, located in the same region. The two married in the early 1900s and their first two children were born in Lodz.

George immigrated to Canada in 1905 to avoid conscription into the Russian army, which at the time mandated Jewish men serve 25 years. After immigrating, George found work in Cobalt, a rapidly growing mining town in northern Ontario. His first job was paymaster in a silver mine employing mostly Slavic workers, and this job may have been related to his fluency in both Slavic languages and English. George later became the owner of a grocery store in Cobalt.

Sarah and their first two children joined George in Cobalt in 1911 where Elizabeth was born in 1915. In 1916, the family made a final move to Toronto, where the rest of their children were born. George owned a candy factory for many years while Sarah was deeply involved in charity work throughout her life in Toronto.

Sarah and George had four sons and four daughters. Remarkably, all four of their daughters went to university in Canada and achieved advanced degrees (MD, DDS, MA), despite restrictive admittance quotas for women and Jews. None of the four boys went to university, largely due to economic circumstances during the Depression3.

Elizabeth graduated from high school at age 15 and attended the University of Toronto for her undergraduate and graduate degrees. She earned her M.D. in 1939 at age 23, one of only 11 women, and the only Jewish woman in her graduating class of 125.

While earning her medical degree, she met Solomon Shankman, who was also attending the University of Toronto. He earned a Ph.D. in chemistry in 1939. Elizabeth and Sol married in 1940, eventually settling in Los Angeles, California, where they had three children: Paul (1943), Janet (1946), and Anne (1950-1993).





Dr. Stern, 3rd row from bottom, 4th image from right

Professional Life and Contributions

Following medical school, Dr. Stern entered a graduate studies program at the University of Pennsylvania School of Medicine from 1941 to 42 focusing on gynecology and obstetrics. She then moved to Los Angeles where she entered her residency in pathology in 1942 at Cedars of Lebanon and Good Samaritan Hospitals, graduated in 1946 and was subsequently certified by the American Board of Pathology.

After her residency, Dr. Stern continued as an associate pathologist at the Cedars of Lebanon Hospital from 1946 to 1949. In 1950 she became Director of Laboratories and Research at the Cancer Detection Clinic of the Cancer Prevention Society in Los Angeles and held this position until 1960. It was at this center that Dr. Stern began her groundbreaking research that occurred during an important transition point in the study of cervical cancer.

In 1950, the Pap test was not yet widely implemented even though cervical cancer was the leading cause of cancer-related death among American women [9]. Like many clinics, the Cancer Detection Center began offering Pap tests in the early 1950s, with increasing numbers of women deciding to have the test throughout the 1950s and 1960s. Dr. Stern witnessed firsthand how the Pap test could be used to diagnose cancer at earlier, more treatable stages, and recognized its potential to reduce patient mortality [10].

She was interested in carefully defining the multiple stages of cervical cancer as there was not a commonly accepted standardized reference for how to interpret Pap test results in the mid-twentieth century. This work was essential for advancing this emerging field of medical science and for women’s health.

The Cancer Detection Center screened thousands of women in Los Angeles each year. Her first peer-reviewed article, “Cytologic Detection of Uterine Cancer in a Cancer Detection Clinic” (1954) included Pap testing results from more than 12,000 women from 1952 to 1953 [10].

In 1961, Dr. Stern was the Research Coordinator for the Project on Hormone Metabolites in Cancer at the University of Southern California Medical School and was hired as the Chief of Cytology4 in the Department of Pathology at the UCLA Center for Health Sciences. The first year of her work at UCLA was unpaid. Although she had been offered a paid position at another institution, she ultimately declined the offer, as it would have taken her away from her family for much of each year.

In 1963, she moved to the recently established School of Public Health at UCLA as an associate researcher in a non-tenure-track faculty position5. This meant that she was required to fund her own research. Dr. Stern’s transfer to the School of Public Health and her non-tenure track position reflected the slow recognition of cytopathology in medicine.

Her lab continued analyzing thousands of patient samples from local clinics in Los Angeles, resulting in many peer-reviewed papers [1, 2, 11-13]. One of the major results of this work was her 1974 paper, “A Cytological Scale for Cervical Carcinogenesis”, that provided detailed descriptions for defining cervical cancer stages from Pap tests and cervical biopsies [1]. Her multi-year studies also demonstrated the link between abnormalities in cervical cell shape and size and risk for cervical cancer. Although controversial at the time, the association of dysplasia to cervical cancer is now generally accepted throughout the scientific community.

In 1965, Dr. Stern was promoted to Associate Professor in Residence, and in 1972 was made Professor in Residence at the UCLA School of Public Health. At this point, she was collaborating with numerous researchers in epidemiology, biostatistics, pathology, and public health, expanding her studies of cervical cancer and receiving professional recognition including: President of the American Medical Women’s Association of Los Angeles County, Branch 23 (1962), Fellow of the College of American Pathologists (1963), UCLA Woman of Science (1968), and International Academy of Cytology Fellow (1971). She was a founding member of the American Society of Preventative Oncology.

In 1977, Dr. Stern published the results of a seven-year study that found a six-fold increase in cervical cancer for women on the high-dose estrogen birth control pill [2]. This disturbing discovery combined with growing evidence of other dangerous side effects, like blood clots, supported the reformulation of a safer, lower-dose pill [14].

In the latter part of her career, Dr. Stern broadened her research to encompass other problems impacting cervical cancer. Although cervical cancer rates had dropped substantially in the US by the 1970s, this drop was not uniform across all communities. Dr. Stern and her colleagues found that in Los Angeles, the highest rates of cervical cancer and the lowest rates of Pap testing occurred in low-income neighborhoods.

The best way to address these issues was through public policy in order to educate patients on the importance of cancer screening and to make these tests available to underserved communities. Dr. Stern helped pilot a community-based clinic to determine the strategies that would make these efforts successful in the long term. In addition to offering free cervical and breast cancer screening, she noted the importance of follow-up calls, free transportation, childcare, and flexible scheduling [3-5]. Her report also stressed the need for bilingual nurses or doctors who could more personally communicate with patients, contributing to a more empathetic style of patient care.

Dr. Stern was also interested in improving the speed and accuracy of Pap testing, as the process of cell collection, staining, and analysis had changed little since the test was developed. She worked with the Jet Propulsion Laboratory, under the management of the California Institute of Technology, to develop a system for digital, automated analysis of Pap tests. As part of this work, she established an innovative, liquid-based sampling technique for Pap testing, which removed non-cervical cells and other debris, making the Pap test easier to analyze [6-8]. This technique represents one Dr. Stern’s most lasting legacies, as it paved the way for an entirely new version of the Pap test, the Liquid Based Pap test, which continues to be used in hospitals, laboratories, and clinics around the world today.

Later Life

Dr. Stern worked at UCLA for 20 years and was known as a brilliant scientist, as well as an excellent mentor and role model. Colleagues thought that she was ahead of her time in terms of her pioneering research on cervical cancer, her concern for the health and well-being of low-income, underserved communities, and her support of women scientists6. Yet like so many women scientists, her contributions have been widely under-recognized.

In 1980 Dr. Stern passed away at home from stomach cancer. As a dedicated scientist, she worked on manuscripts and corresponded with colleagues up to the week before her passing. Following her death, Dr. Dorothy Rosenthal continued their research on improving the Pap Test, working with the Jet Propulsion Laboratory to complete these studies. Unfortunately, Dr. Stern’s other projects remained unfinished, and her scientific biorepository, including carefully curated slides denoting unique stages of cervical cancer, has been lost.

Just prior to her death, the UCLA School of Public Health Division of Epidemiology established and endowed The Elizabeth Stern Cancer Epidemiology Lectureship to be awarded annually. Dr. Stern was able to select the first speaker. In her memory, Sol Shankman established the Dr. Elizabeth Stern bursary for women students of minority status at University of Toronto. In 2014 he passed away at age 98.

Sources:

Janet Williamson
Ellen Weinzapfel
Paul Shankman
Gail Lord
Laura Lamb
Sandor Stern
Ruth Stern
Janice Kreiger
Kathy Leslie
Ken Castleman


Footnotes:

1https://blogs.scientificamerican.com/voices/one-more-pioneering-woman-in-science-youve-probably-never-heard-of/ by Ellen Elliott (Weinzapfel)

2Dysplasia refers to mild abnormalities in cervical cell shape and size. All cervical cancers start with dysplasia, but dysplasia does not always lead to cancer. In many cases, the cellular abnormalities resolve on their own over time. However, it is not possible to tell which cases of dysplasia will resolve as opposed to progress to cancer. So, when dysplasia is detected via Pap test, physicians keep a close eye on the patient to prevent cancer progression.

3Education was heavily subsidized in Canada in the first half of the 1900s which made it possible for Dr. Stern and her sisters to attend university. However during this time most men, including Dr. Stern’s brothers, had to go into the workforce filling what entry-level jobs, mostly for unskilled laborers, were available.

4The terms “pathology” and “cyotopathology” and “cytology” are used interchangeably by some experts and are treated as separate entities by others.

Pathology: The field of medicine focused on the diagnosis of disease.

Cytopathology, or Cytology for short: A subset of pathology, focused on the study of cells to diagnose disease.

Context: The fields of pathology and cytopathology grew along side each other. This is why the two terms are often used interchangeably. Further, most modern subsets of pathology, pulmonary pathology and renal pathology, are largely based in analysis of biopsies and/or cells, making them at least partially cytopathology specialties.
In the text here, the terms “cytopathology” or “cytology” are used as much as possible to avoid confusion.

5Tenure and non-tenure track positions are very different in academia. Tenure-track positions are more desirable and more research-oriented with job security and higher salaries. Receiving tenure requires a track record of success in publications, funding, and teaching. Universities and colleges distinguish these positions that require a long-term funding horizon and lifetime employment from non-tenure track appointments that are typically short-term, pay far less, and focus on teaching. There are also non-tenure track positions with a focus on research for faculty members who obtain external grant funding to support their positions.

‪As a non-tenured faculty member, she obtained external funding to supprt her own position in the UCLA School of Public Health. In addition, she taught courses and was a graduate student advisor. ‬ ‬‬‬‬Despite the lack tenure, Dr. Stern vigorously pursued and achieved many of her goals.‬‬‬‬‬‬‬‬‬‬‬‬‬

6From Ellen Weinzapfel’s interviews and correspondence in 2017 with Dr. Dorothy Rosenthal (Johns Hopkins University), Dr. Marylin Winkleby (Stanford University), and Dr. Anna Wu (University of Southern California), all of whom worked with Dr. Stern at UCLA.

References:

1. Stern, E., et al., A cytological scale for cervical carcinogenesis. Cancer Res, 1974. 34(9): p. 2358-61.
2. Stern, E., et al., Steroid contraceptive use and cervical dysplasia: increased risk of progression. Science, 1977. 196(4297): p. 1460-2.
3. Stern, E., et al., Papanicolaou testing and hysterectomy prevalence in low-income communities: a survey in Los Angeles County. Natl Cancer Inst Monogr, 1977. 47: p. 113-9.
4. Stern, E., et al., "Pap" testing and hysterectomy prevalence: a survey of communities with high and low cervical cancer rates. Am J Epidemiol, 1977. 106(4): p. 296-305.
5. Misczynski, M. and E. Stern, Detection of cervical and breast cancer: a community-based pilot study. Med Care, 1979. 17(3): p. 304-13.
6. Rosenthal, D.L., et al., Endocervical columnar cell atypia coincident with cervical neoplasia characterized by digital image analysis. Acta Cytol, 1982. 26(2): p. 115-20.
7. Rosenthal, D.L., et al., A simple method of producing a monolayer of cervical cells for digital image processing. Anal Quant Cytol, 1979. 1(2): p. 84-8.
8. Stern, E., et al., An expanded cervical cell classification system validated by automated measurements. Anal Quant Cytol, 1982. 4(2): p. 110-4.
9. Safaeian, M., D. Solomon, and P.E. Castle, Cervical cancer prevention--cervical screening: science in evolution. Obstet Gynecol Clin North Am, 2007. 34(4): p. 739-60, ix.
10. Stern, E. and N.P. Menoher, Cytologic detection of uterine cancer; in a cancer detection clinic. J Am Med Womens Assoc, 1954. 9(11): p. 343-9.
11. Stern, E., Cytohistopathology of cervical cancer. Cancer Res, 1973. 33(6): p. 1368-78.
12. Stern, E. and P.M. Neely, Dysplasia of the Uterine Cervix. Incidence of Regression, Recurrence, and Cancer. Cancer, 1964. 17: p. 508-12.
13. Stern, E. and P.M. Neely, Carcinoma and Dysplasia of the Cervix: A Comparison of Rates for New and Returning Populations. Acta Cytol, 1963. 7: p. 357-61.
14. Liao, P.V. and J. Dollin, Half a century of the oral contraceptive pill: historical review and view to the future. Can Fam Physician, 2012. 58(12): p. e757-60.