Giants in Obstetrics and Gynecology

ajog.org

Giants in Obstetrics and Gynecology Series:
a profile of Mary Lake Polan, PhD, MD, MPH
Roberto Romero, MD, DMedSci

Dtree stumps with their .22 riﬂes. Froman early age, she found “the world
beyond the coalmines and mountains
magnetic,” as she describes in her 2016
book, A Doctor’s Journey: What I
Learned about Women, Healing andMyself in Eritrea1.
Her large Jewish family in Huntington comprised her father’s relatives. She
recalls being raised among her two
younger siblings and a dozen cousins,
whose fathers, unlike her physician father, were connected to the Polan familybusiness where they manufactured
bombsights during World War II, andDr Mary Lake Polan
subsequently, optical lenses. The
mothers of all the children were surrogate mothers to all the cousins. When it
came to issues of discipline, “they would paddle you or correct you regardless of who your parents were,” Mary Lake
recalls. The cousins were more like siblings and have
Early life
Born in Las Vegas, New Mexico, Mary Lake was the eldest remained so throughout their lives.
Mary Lake’s interest in medicine came quite naturally—herchild of a ﬁrst-generation Lithuanian father, an ophthalmologist then serving in the United States Army, and a ﬁrst- father often took her with him on Sunday mornings forgeneration Protestant, Wisconsin-born mother of Norwe- rounds on surgical patients at the hospital. Her ﬁrst job at thegian descent. Her parents had met and married while her age of 17 was as a summer ward clerk at the local hospital,
father was a resident and her mother a nurse at the University where she managed the phones and paperwork on a surgicalof Wisconsin teaching hospital. Mary Lake was born during ward. Mary Lake says that her father was loving and supthe Second World War while her father was stationed in New portive and made her feel that she could achieve anything to
Mexico before his posting overseas for two years in a military which she aspired.
It all sounds pretty idyllic, except for one thing. Mary Lakehospital in the Azores.
Mary Lake spent her early life in Huntington, West Vir- perceived a much more rewarding and exciting world outside
ginia—an idyllic small town stretched out along the Ohio the Appalachian region of the country, in part because herRiver—where the front doors were left unlocked, children father had often exposed their family to the more metrowalked to and from school with friends, and lunch was eaten politan and cosmopolitan regions of the country, which
at home. On the weekends, since Mary Lake was nine years included periodic trips to New York City, Miami, and theold, her father took her and her younger brother Chuck into Caribbean islands. In addition to being the already voracious
the mountains of West Virginia where they shot bottles off reader she has remained throughout her life, Mary Lake knewthat she had a great deal to learn from the wider world. “I
From the Perinatology Research Branch, Eunice Kennedy Shriver Na- would have done anything to get out of West Virginia” and “Iftional Institute of Child Health and Human Development, National In- there’s some way to get there, I’m ready to go anywhere” arestitutes of Health, US Department of Health and Human Services, Detroit, two of a number of her utterances that begin to describe theMI.
life of Mary Lake Polan.
Received Sept. 20, 2021; accepted Sept. 21, 2021.
Her chance came during the ninth grade in Huntington.
The author reports no conﬂict of interest.
At Mary Lake’s request, her parents surveyed several
Corresponding author: Roberto Romero, MD, DMedSci. rr.ajoged@
Southern boarding schools, but ultimately, they sent her togmail.com
the Emma Willard School—a private school for girls in
0002-9378/$36.00
Troy, New York, founded in 1814. At ﬁrst, Mary Lake told
Published by Elsevier Inc.
me that she felt more like the Appalachian girl she wished tohttps://doi.org/10.1016/j.ajog.2021.09.023
leave behind. Her fellow classmates were, at least in her
r Mary Lake Polan is a physicianscientist, clinician, educator, andacademic leader who has produced
pioneering work on the role of cytokines and inﬂammation in reproduction,
speciﬁcally in implantation and ovulation. She served as Professor and Chairof the Department of Obstetrics andGynecology at Stanford University, promoted clinical excellence, and established a unique program to treat womenwith obstetrical ﬁstulas and to train
surgeons in the East African country of
Eritrea. Dr Polan is an elected memberof the National Academy of Medicine, anauthor, and a humanist. For her many
contributions that have changed the livesof women, Dr Polan is recognized as a
Giant in Obstetrics and Gynecology.

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mind, more sophisticated and worldly than she envisioned
herself. For example, in class one day, her French pronunciation of the Battle of Agincourt was corrected by her
teacher. In that moment, she promised herself that she
would learn French and never again be embarrassed bymispronouncing a French word. And she did learn,
spending her junior year of college in Paris with the Smith
College Junior Year Abroad Program. Mary Lake’s talent tolive up to her father’s expectations soon showed itself as anindicator of what life thereafter would be like for her. The
Emma Willard School and its student life became somethingthat she came to enjoy and admire. Years later, her devotion
to the merits of all-girls schooling caused her to remainboth supportive of the School and connected to its leadership and her classmates.

Elizabeth Blackburn (Nobel Laureate for her discoveries ofthe molecular nature of telomeres). Mary Lake’s work
focused on the isolation and characterization of the circular
mitochondrial DNA of Drosophilia melanogaster2 (Figures 1
and 2).

An education in Connecticut: college andgraduate school
Mary Lake attended Connecticut College, then a private
liberal arts women’s college, in New London. The school
was supportive of students charting their own educationalcourse, and Mary Lake began after her freshman year,
spending a summer in Switzerland with the “The Experiment in International Living” program. That summer trip
was quickly followed by her junior year in Paris. After
graduating from Connecticut College with a major inchemistry, Mary Lake migrated 50 miles down the Connecticut coastline to the Department of Molecular
Biophysics and Biochemistry at Yale University, where shecompleted her PhD in molecular biophysics andbiochemistry, followed by a postdoctoral fellowship in the
Department of Biology in the laboratory of Dr Joseph Gall.
Dr Gall, who developed in situ hybridization, was awarded
the Albert Lasker Award in 2006 and is known forencouraging women to pursue a career in science. His
trainees include Dr Joan Steitz (Lasker-Koshland awardee
for pioneering contributions to RNA biology) and Dr

Yale University Medical School: residency andfellowship
At this juncture, medical school seemed to be a better idea
than a laboratory career—Mary Lake found that talking tocolleagues about the experiments was more fun thanactually doing the research. Yale Medical School offered alogical path to medicine, as there were no exams and it
only required a passing grade on Boards Part 1 and 2 anda thesis project to graduate. Having completed her PhD
thesis at Yale, Mary Lake ﬁnished medical school in three
years—an important bonus, because her father had told
her that he was not willing to pay for medical school.

FIGURE 2

Microscopy revealed distinctive circular forms in
MtDNA

FIGURE 1

Behold the fruit fly: molecular revelations of MtDNA

While working in the laboratory of Dr Joseph Gall at Yale University in the
1970s, Dr Mary Lake Polan analyzed and described unique genetic
aspects of the fruit fly, reported in the study “Isolation and characterization of mitochondrial DNA from Drosophila melanogaster.”2ª1973 by The Rockefeller University Press. Polan et al.2

ª1973 by The Rockefeller University Press. Polan et al.2

MtDNA, mitochondrial DNA.

MtDNA, mitochondrial DNA.

Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD,
MD, MPH. Am J Obstet Gynecol 2022.

Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD,
MD, MPH. Am J Obstet Gynecol 2022.

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Giants in Obstetrics and Gynecology

FIGURE 3

FIGURE 4

Mary Lake and her son Scott visiting Tehran, Iran

Bridging science, history, and the literary arts

Photo courtesy of Dr Mary Lake Polan.
Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD,
MD, MPH. Am J Obstet Gynecol 2022.

Undertaking only three years of tuition was critical, andshe spent her two preclinical years of medical school
working part-time as a laboratory technician in Dr Gall’s
lab to support herself.
There were two other major advantages to staying in New
Haven. First, the Yale curriculum was ﬂexible, allowing MaryLake to spend three months at the University of Oxford, England in the Radcliffe Inﬁrmary and the John Radcliffe Hospitalcompleting her obstetrics and gynecology and pediatric clinicalclerkships during her third year of medical school. Second,
while conducting research in the Department of Dermatology
for her doctoral thesis at Yale, she met her future husband, Dr
Joseph Smith McGuire, Professor of Dermatology.
Mary Lake remained at Yale for her residency. Indeed, she
was the ﬁrst woman to graduate from the residency programin the Department of Obstetrics and Gynecology. She had theopportunity to spend three months as an elective during thelast year of residency in the hospitals in Shiraz—the “City ofRoses” —in southern Iran. The Iranian spring included trips
to Isfahan and Persepolis—a UNESCO World Heritage Site
located 60 kilometers from Shiraz; its ruins date back to 515
BC. Mary Lake’s fascination with Iran continued–in 2005, shereturned to Tehran to participate in an IVF Scientiﬁc Meetingwith her son Scott (Figure 3). The mystique of Persia wastranslated into Mary Lake’s medical mystery novel, SECOND
SEED, published in 19873 (Figure 4).

A Fellowship in Reproductive Endocrinology andInfertility
Louise Brown, the ﬁrst in vitro fertilization baby, was born on
July 25, 1978. The excitement of the new infertility technologies drew Mary Lake to a reproductive endocrinology andinfertility fellowship with Drs Nathan Kase and Alan
DeCherney, who worked with Drs Harold Behrman andRichard Hochberg conducting bench research in

Inspired during a visit to the historic city of Shiraz in southern Iran, Dr
Polan wrote a medical mystery novel Second Seed.3ª1988. Image of the paperback reproduced with permission by St.
Martin’s Press.
Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD,
MD, MPH. Am J Obstet Gynecol 2022.

endocrinology.4 The fellowship was followed by a faculty
appointment as Assistant Professor at Yale, where she initiateda National Institutes of Health-sponsored research programon the hormonal function of human granulosa-luteal cells.5,6
Yale also brought priceless opportunities for relationships
and mentors. There, she married Dr McGuire, a distinguishedphysician and teacher who, remarkably, came from Mary
Lake’s native West Virginia. From his early life as a coalminer’s son, Joe became a highly regarded Professor of Pediatric Dermatology at Yale and later at Stanford. As amentor, he encouraged Mary Lake to fully realize her potential in the world of medicine. Her other mentors at Yale
were Drs Joan Steitz, Florence Haseltine, and Leon Speroff,along with Drs DeCherney and Kase. The latter threephysicians, previously recognized as Giants in Obstetrics andGynecology, have been important mentors to many inobstetrics and gynecology.7e9
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FIGURE 5

An innovative study in implantation

A study of importance emerged during her tenure at Stanford University, reflecting a significant research interest in implantation.22
Reproduced with permission. Krüssel et al.
Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD, MD, MPH. Am J Obstet Gynecol 2022.

Throughout her residency and fellowship, which
included time as a fellow in gynecologic oncology, she met
and worked for Dr John McLean Morris, a Yale gynecologist who had been raised in China. The child of Christian
missionaries, Dr Morris—world renowned for his discovery of testicular feminization and postcoital contraception(morning-after pill)—introduced Mary Lake to the YaleChina Program, which had sponsored Yale undergraduates to teach English to middle-school students in
Changsha, a city of ﬁve million people in central Hunan
Province, since 1914. As a junior faculty member, Mary
Lake, her husband Joe McGuire, and their two children—
seven-year-old Joshua and ﬁve-year-old Lindsay, spent fourmonths in 1986 at the Second Afﬁliated Hospital in
Changsha teaching students and residents. After enrollingthe children in a Chinese daycare, Mary Lake, then fourmonths pregnant with their third child, taught, lectured,and performed infertility surgeries. On returning to Yale,her research interests expanded to include cytokines andthe relationship of interleukin (IL)-1 to reproductivefunction.10e12

Professor and Chair at Stanford University Schoolof Medicine
In 1990, Mary Lake moved to Palo Alto, California withher husband and their three young children to become
the Chair of the Department of Obstetrics and Gynecology as the Katherine Dexter McCormick and Stanley
McCormick Memorial Professor at Stanford University
School of Medicine. This appointment opened an evenwider world of interest and service with regard to
women’s health for Mary Lake. During her 16 years inthat capacity, she joined the boards of Wyeth—a prestigious pharmaceutical company and Quidel—a maker of
rapid diagnostic tests; she was elected to The Institute ofMedicine (now the National Academy of Medicine) andFIGURE 6

A murine study of molecular mechanisms in implantation

A novel finding in implantation that informed our field came forth from Dr Mary Lake Polan’s laboratory at Stanford University in the late 1990s.23
Reproduced with permission. Simón et al.
Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD, MD, MPH. Am J Obstet Gynecol 2022.

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Giants in Obstetrics and Gynecology

served on its Governing Council and on numerous National Institutes of Health and other professional association committees; she lectured and testiﬁed broadly about
women’s health issues. During a sabbatical, Mary Lake
returned to school at the University of California, Berkeley, where she obtained a Master’s in Public Healthdegree and became interested in obstetrical ﬁstulae.
Signiﬁcantly, in 2002, she founded the Eritrean Women’s
Project, as described earlier, resulting in novel reports ofsurgical techniques and social interventions to preventand treat obstetrical ﬁstulas resulting from birthtrauma.13e15

A role for interleukin-1 in ovulation andimplantation

FIGURE 7

Sabbatical: reflections on women’s reproductive
healthcare in Eritrea1

Ovulation is a sterile inﬂammatory process, and a role
for the IL-1 system was envisioned in the early 1990s
after the identiﬁcation of the cytokine in human follicular ﬂuid16,17 and the characterization of the humanintraovarian IL-1 system.18 Mary Lake’s studies showedthat the production of IL-1 by peripheral blood monocytes and ovarian cells increases during the luteal phaseof the menstrual cycle and produces a midcycle IL-1
surge in humans.19 Her laboratory at Stanford demonstrated the presence of the IL-1 system in the mouse
ovary during follicular growth, ovulation, and lutealization20 and of time-dependent inhibition of ovulation by
the natural IL-1 receptor antagonist.21 Much of this work
was done in collaboration with Professor Carlos Simón, amember of her team at Stanford, who has now become atowering ﬁgure in reproductive endocrinology and infertility. The focus then turned to the role of IL-1 in implantation after showing that the blastocysts produce
IL-122,23 (Figure 5) and that the administration of thenatural IL-1 receptor antagonist prevented embryonic
implantation by a direct effect on the endometrial
epithelium24 (Figure 6).

Mary Lake Polan, the author
Several years after writing her novel Second Seed, Mary Lake
published A Doctor’s Journey: What I Learned about Women,
Healing, and Myself in Eritrea1—a story of friendship between
physicians in the United States and doctors and nurses in
Eritrea, which began on a winter night in 2002 (Figure 7).
With this ﬁrst trip to East Africa, Mary Lake initiated theEritrean Women’s Program, created to surgically treat womenwith obstetrical ﬁstulas and to train Eritrean surgeons torepair the ﬁstulas; it was an endeavor lasting nearly two decades. This excerpt is Mary Lake’s description of her ﬁrst
arrival in Asmara, which is the capital of Eritrea—a small
country in the Horn of Africa on the Red Sea, tucked between Sudan, Ethiopia, and Djibouti:

Author Mary Lake Polan chronicles her sabbatical in Eritrea, relating thesignificant outcomes for pregnant women and their children affected byobstetrical fistulas and other birth traumas and the restorative surgeries
performed by an international medical team, in her 2016 memoir, A
Doctor’s Journey: What I Learned about Women, Healing and Myself in
Eritrea.1ª2016 by Mary Lake Polan. Image reproduced with permission.
Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD,
MD, MPH. Am J Obstet Gynecol 2022.

“After the plane had hopscotched from San Francisco toFrankfurt to Jeddah, Saudi Arabia, the pilot’s
announcement—‘We’re descending for our landing in
Asmara’—was an electric jolt waking me from theintermittent dozing of the twenty-four-hour trip.
Deprived of sleep, hair uncombed, I tried unsuccessfully to separate excitement from anxiety.
“The airplane door swung inward. Freezing night air
washed over me. In my Out of Africa-inﬂuenced
imagination, it should have been hot, but on thisJanuary night, I shivered in my cotton jacket as wedescended the roll-up staircase onto a cracked concrete
runway. Asmara Airport read the sign on the wall of a
two-story building a couple of hundred yards away,
visible in the yellow glow from the airport windows.
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Giants in Obstetrics and Gynecology“I’d been dreaming of this moment for a long time.
This trip was the goal I had worked toward over the last
two years, ever since the idea of bringing American
surgeons to treat women injured in childbirth became
the focus of my sabbatical studies in international
public health. I was then Chair of the Ob-Gyn
department at Stanford University, and I had become
fascinated by the problem of obstetrical ﬁstula—aterrible situation caused by prolonged labor which left awoman with a stillborn baby and constantly leaking
urine from a hole torn in her bladder.

ajog.org

FIGURE 8

A memorable day“Five American gynecologists, including me, were here
because of my efforts. After months of work andplanning, I had ﬁnally persuaded two foundations to
support this two-week trip to Eritrea..
“The heavy metal door to the terminal clanged open andwe followed an animated group of Eritrean men andwomen into a bare room, painted a dull brown. The
room was lit by hanging bulbs and smelled of stalecigarette smoke. Two unsmiling ofﬁcials sat behind glass
panels at the far end, the sleeves of their uniform shirts
rolled up to the elbow. They were slowly and systematically examining documents handed to them by the
incoming passengers. The Eritrean passengers chatted
excitedly as they greeted one another and the bordercontrol guards behind the glass. Tired, we held backuntil one of the guards beckoned. One by one, we
handed over our passports and visas to be stamped andwere ushered into the Customs area. We waited as theboxes of donated medical sutures, antibiotics, and surgical retractors were brought from the plane and piled
up around us.
“I began to sweat. What if nobody comes to meet us?

Mary Lake and her husband Frank at their wedding, standing on a bluff
overlooking the ranch.
Photo courtesy of Dr Mary Lake Polan.
Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD,
MD, MPH. Am J Obstet Gynecol 2022.

With Mary Lake’s planning, the couple also collaborated onfamily trips of up to 40 children, spouses, signiﬁcant others,
and grandchildren to Kenya and South Africa, to the glacial
waters of Alaska, and to the beaches of the Galapagos Island,
to name a few of their excursions.

FIGURE 9

Visiting with a well-known personality inbroadcasting“We were here because I wanted to work in Africa. I was
drawn to this strange and unknown world. I felt acutely
responsible for the three other women docs and for the
single man in the group. I silently prayed we would be
able to accomplish our goal of successful surgeries and,equally important, that we’d be safe in this very foreigncountry..
“Please, God, let someone be here to tell us what to do andtake care of us.”1

An international presence
Before COVID-19 interfered with world travel, Mary Lakeencouraged her second husband, Frank Bennack Jr, (Figure 8)
to take trips that he probably would not have taken without
her urging. They ﬁrst journeyed in 2008 with the New York
Philharmonic Orchestra to Pyongyang, Democratic People’s
Republic of Korea, when Frank served as Chairman of New
York’s Lincoln Center for the Performing Arts. Several years
later, they traveled to Havana, Cuba, in October 2016, again
with a group from the Lincoln Center.
174 American Journal of Obstetrics & Gynecology FEBRUARY 2022

Barbara Walters hosted the Hearst affiliate ABC’s talk show The View
from 1997 until 2014. L-R: Ms Barbara Walters, Mr Frank Bennack Jr,
and Dr Mary Lake Polan. Photo courtesy of Dr Mary Lake Polan.
Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD,
MD, MPH. Am J Obstet Gynecol 2022.

ajog.org

FIGURE 10

Encountering a legend in television, film, andpublishing

Oprah Winfrey is editor-in-chief of O, The Oprah Magazine, published byHearst. L-R: Dr Mary Lake Polan, Ms Oprah Winfrey, and Mr FrankBennack Jr. Photo courtesy of Dr Mary Lake Polan.
Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD,
MD, MPH. Am J Obstet Gynecol 2022.

Remarkably, Mary Lake was destined to meet prominent
political leaders and media luminaries (Figures 9-11). Her
husband Frank is Executive Vice Chairman and former Chief
Executive Ofﬁcer of Hearst, one of the nation’s largest publishing companies, and an accomplished author.

FIGURE 11

Attending a History Channel symposium, 2019

L-R: William J. Clinton, former US president; Mr Frank A. Bennack Jr; Dr
Mary Lake Polan; and George W. Bush, former US president.
Photo courtesy of Dr Mary Lake Polan.
Romero. Giants in Obstetrics and Gynecology Series: a proﬁle of Mary Lake Polan, PhD,
MD, MPH. Am J Obstet Gynecol 2022.

Giants in Obstetrics and Gynecology
After her marriage to Frank, Mary Lake moved to New
York City, accepting an appointment as Visiting Professor atColumbia University School of Medicine. Subsequently,
coming full circle, she returned to Yale in 2014 as Professor of
Clinical Obstetrics, Gynecology, and Reproductive Sciences in
the School of Medicine.
Having contributed to the ﬁeld of women’s health in thelaboratories, clinics, and operating rooms of the United States,
Iran, China, and Eritrea, Mary Lake says, “Living in a different
country, working with physicians from other cultures, withvery different training, forces you to be ﬂexible, open to newtechniques and, importantly, new ways to relate to people.
Unconstrained by familiar social hierarchies, you are thrownback on yourselfewho you essentially areeand you discoverunexpected capabilities. It is a freedom to give back that becomes addictive, and it has been a guiding theme throughout
my life, facilitating friendships between colleagues here athome and in countries around the world. Yes, it has allowed
me to help women, but as importantly, it has enriched my life.”
In the full spirit of giving, Mary Lake and Frank have endowed
Chairs at Stanford and Yale, both dedicated to the area ofgynecologic oncology in the respective Departments of Obstetrics and Gynecology.
The American Journal of Obstetrics and Gynecology recognizes Dr Mary Lake Polan’s professional contributions as aphysician, scientist, leader, and role model.
ACKNOWLEDGMENTS
This proﬁle is based on conversations with Dr Mary Lake Polan and Mr
Frank Bennack Jr during the COVID-19 pandemic in 2020 and 2021. The
article was read by Dr Polan before publication.
-

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3. Polan ML. Second seed. Bronx, NY: Charles Scribner & Sons, Inc; 1987.
4. Polan ML, DeCherney AH, Haseltine FP, Mezer HC, Behrman HR.
Adenosine ampliﬁes follicle-stimulating hormone action in granulosa cells
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Human testis cytosol and ovarian follicular ﬂuid contain high amounts ofinterleukin-1-like factor(s). Mol Cell Endocrinol 1988;58:221–30.
17. Wang LJ, Norman RJ. Concentrations of immunoreactive interleukin1 and interleukin-2 in human preovulatory follicular ﬂuid. Hum Reprod
1992;7:147–50.

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24. Simón C, Pellicer A, Polan ML. Interleukin-1 system crosstalk between embryo and endometrium in implantation. Hum Reprod
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