Development of a California Research Organization: Sanford Burnham Prebys Medical Discovery Institute

By Nancy Beddingfield, Nina Fishman and Eva Engvall

This book tells the story of the founding and development of a remarkable research institute, primarily from the scientists' view but with enough context to validate its earned reputation as a research powerhouse.

The Institute's origin as "La Jolla Cancer Research Foundation" is told by the Founders' daughter Nina Fishman. Its evolution from modest beginnings to a major research organization unfolds in interviews with scientists who spent major parts of their careers at the Institute. Their enterprise--competing for grant funding, conducting groundbreaking science, and training new scientists--built the Institute's success.

Much of the success of the early Institute and its staff members was the result of the unique organization and structure of shared resources, which allowed individual laboratories to pursue technically advanced research, thereby making them highly competitive in their fields.

This is also an "only-in-America" story, a story of how the highly competitive research funding allocated by the U.S. Congress, and supplemented by individual donors, can make it possible for a group of dedicated scientists to build a successful research Institute.

We, the authors, hope this book will share what it was like to work in this extraordinary place, with people doing things that had never been done before, and hopefully inspire others to pursue paths that ultimately make a difference. We have donated our work to The Fishman Fund at Sanford Burnham Prebys Medical Discovery Institute.

• Language: English
• Publisher: BookBaby
• Release date: Dec 24, 2021
• ISBN: 9781667819181

Book preview

Title

Dedicated to our scientists, medical researchers,

and to all who support them.

© 2021

ISBN: 978-1-09838-672-6

eISBN: 978-1-6678191-8-1

The authors have gifted their work to the Fishman Fund.

All rights reserved. This book or any portion thereof may not be reproduced or used in any manner whatsoever without the express written permission of the publisher except for the use of brief quotations in a book review.

CONTENTS

Authors’ note

Founding

Part One The Scientists

1. Principal Investigators

Part Two The Institute

2. Training

3. Shared Resources

4. Leadership

5. Centers And Programs

6. Facilities

7. Community

Acknowledgements

Appendices

Board Chairmen

Scientific Advisors

Institute Annual Symposia

Rare Disease Day Symposia

Fishman Fund Awardees

Authors’ note

Our specific aim with this story is to tell the origin and evolution of a very special research organization. We have interviewed some of the early and long-time members of the scientific staff, not only the Principal Investigators but also members of Shared Resources, who have been essential to the success of the Institute. We spoke with members of various non-scientific departments, including Administration, and Buildings and Grounds. Key events and dates referenced in historic Institute newsletters, annual reports, other institute publications and website were invaluable to our process. The result is an eclectic recollection, not a formal Institute history. We are:

Nancy Beddingfield, who joined the Institute in 1980 when it was still in startup mode. Nancy served more than 27 years in support of the Institute, most significantly as Assistant to Dr. Erkki Ruoslahti from 1980 to 2002. In later years, Nancy served as Director of Public Affairs.

Nina Fishman, daughter of the Founders of the Institute, Dr. William and Mrs. Lillian Fishman. For more than a decade, Nina has been directly involved with the Institute’s NCI Cancer Center as a member of its Community Advocacy Board. Nina’s career over the years has centered on organizational effectiveness, leadership development, and training.

Dr. Eva Engvall joined the Institute as one of the earliest recruited Principal Investigators and served as an active contributor for many years. In addition to running her own research laboratory, Eva established the Institute’s Animal Research Facility, supervised a growing portfolio of Shared Resources, and implemented professional training for postdoctoral fellows.

Text note:

1976 – 1996 – La Jolla Cancer Research Foundation

1996 – 2005 – The Burnham Institute

2005 – 2010 – The Burnham Institute for Medical Research

2010 – 2015 – Sanford Burnham Medical Research Institute

2015 – Sanford Burnham Prebys Medical Discovery Institute

The Founding chapter and a few writeups from the early days refer to "La

Jolla Cancer Research Foundation and LJCRF". Other appellations are

simplified to Institute throughout the text.

Discovery Garden outside Building Three – drawing by Francesca Marassi

FOUNDING

Nina Esther Fishman

Founding of the Sanford Burnham Prebys Medical Discovery Institute

(formerly known as La Jolla Cancer Research Foundation; The Burnham Institute; The Burnham Institute for Medical Research; Sanford Burnham Medical Research Institute)

The Sanford Burnham Prebys Medical Discovery Institute (Institute) is one of the world’s exemplar organizations in the field of basic biological research, translational medicine, and organizational innovation. The Institute has attracted a stellar cast of principal investigators, a hard-working cadre of postdoctoral candidates, and an enthusiastic support staff, exceeding 1,000 employees in 2010. It has an international, well-earned reputation for scientific research and discoveries and consistently ranks among the top research institutions worldwide based on peer citations of published research.

The centerpiece of scientific pursuit has always been its Basic Cancer Center. First funded by a National Cancer Institute (NCI) Planning Grant in 1979, then designated as an NCI Basic Cancer Research Center in 1981, this prestigious designation has been maintained for nearly 40 years.

From its origins in cancer, the Institute developed three other major areas of disease-focused discovery: the Del E. Webb Center for Neurosciences and Aging; the Infectious and Inflammatory Disease Center, and the Sanford Children’s Health Research Center. The Institute is also home to the Conrad Prebys Center for Chemical Genomics, providing the infrastructure and services for early-stage drug discovery.

The Institute ~ 1999

Located in what has become the heart of the biotech industry on land facing the Pacific Ocean, shaded by a grove of majestic Torrey Pines, the Institute provides a stimulating environment for scientists who channel their disciplined curiosity into investigating the root causes of chronic diseases. Within a two mile radius, neighbors include the Salk Institute for Biological Studies (Salk), The Scripps Research Institute (Scripps), University of California at San Diego (UCSD), and a host of noteworthy biotech and pharmaceutical companies.

The Institute was founded in 1976, when most of the Torrey Pines Research Mesa was undeveloped. At its inception, the Institute lacked the presence, prestige, and funding of the Scripps, Salk, or of UCSD. It began seemingly from nothing. How did this happen? To answer this question, we need to go back to the organization’s roots, to the people who planted the seeds that created those roots and founded an upstart organization called The La Jolla Cancer Research Foundation.

That an outstanding basic research institution began from scratch, survived, and flourished, has amazed many observers. It began from the vision of my parents, Dr. William Fishman and his wife Lillian, whose perseverance, integrity, and creativity won the support of the community. With the help of that community, the government, and a hard-working scientific staff, the La Jolla Cancer Research Foundation succeeded against all odds. Both Lil and Bill were master gardeners and understood that a certain amount of toil is necessary to bring in a harvest. They worked tirelessly to create the La Jolla Cancer Research Foundation. My belief is that they would be delighted to know that the organization they founded and nurtured has developed in amazing ways, fulfilling their dreams, and no doubt, beyond. If it were possible, they would profusely thank everyone who has sustained the organization and its vision.

A Little Background about the Fishmans

Dr. Fishman had been a leading scientist for 28 years at the Tufts University School of Medicine in Boston, where he served as its first Director of Cancer Research. He was awarded over $2,000,000 in grant funds from the National Cancer Institute, a fortune in those days, to pursue his research on oncodevelopmental science. This award expressed the government’s and his peers’ confidence in his ideas. Unfortunately, he learned, to his dismay, that the administration of Tufts University wanted to earmark those funds for different purposes, and consequently enforced the university’s mandatory retirement policy on Dr. Fishman.

Bill Fishman, Founder and Director,

NCI Cancer Center at Tufts University

The experience at Tufts Medical School left Dr. Fishman with two beliefs: first, he would have to take his individual project grant and research to another location; and second, he would at all costs avoid the type of intramural power politics, which sometimes characterize academic and other institutions. Although he received this major grant due to the merit of his ideas, he knew he could not bring these ideas to fruition unless his work was situated in an organization supportive of his efforts. This realization led to his determination to create a new organization; one that would support scientists, not pit them against each other. His passion to reduce bureaucracy and reward merit would eventually translate into the minimalist organizational structure of the La Jolla Cancer Research Foundation. Instead of university-style departments, work was centered on the Core Research of the Laboratories and their Principal Investigators. The Foundation’s small size also encouraged such capabilities as sharing resources and working across boundaries from the very beginning and encouraging teamwork at every level. Every person, including maintenance and other support staff, was treated as a valuable member of the team.

A Unique Founding Focus: Oncodevelopmental Biology

Every ultimate fact is only the first of a new series. — R.W. Emerson

Dr. Fishman included the quote above in LJCRF’s first brochure published in 1977. It is from an essay entitled, The Circle. Was he thinking of cancer cells? Or the infinite potential of medical research?

A series of discoveries, both here and abroad, led to the then innovative concept of oncodevelopmental biology. In 1974, Dr. Fishman made the discovery that a pregnancy protein could be detected in adult human tumor tissue. He found placental alkaline phosphatase, an enzyme normally expressed in the placenta during the first trimester of pregnancy, in a man’s lung tumor. The Regan isoenzyme, named for the patient, confirmed for Dr. Fishman that cancer development (oncology) was inextricably linked with normal development (ontogeny). His work, along with that of others, defined a new field in cancer research: oncodevelopmental biology, which combined the study of cancer development with that of the development of normal cells.

Dr. Fishman became a founding member of the International Society for Oncodevelopmental Biology and Medicine (ISOBM) in 1973. Known today as the International Society of Oncodevelopment and BioMarkers, ISOBM continues to publish the scientific journal co-founded by Dr. Fishman, published today as Tumor Biology. It would be at an ISOBM conference in 1976 where Dr. Fishman would spend time with Dr. Erkki Ruoslahti, a conference participant invited to speak about onco-fetal proteins. And, in 1979, ISOBM would select the Institute as its North American headquarters.

Finding a Home in La Jolla

While attending a scientific conference in San Diego, Dr. Fishman was struck by the entrepreneurial climate as well as the physical beauty of the city. On a personal level, both he and his wife were Westerners, and much of the family on both sides lived in California and Western Canada. When Lil said, I could live here, Dr. Fishman put his plan into action. Leaving Boston began to feel like coming home rather than leaving home. Still, the transition was immense for two people of early retirement age…who did not let societal stereotypes about age guide their actions, had a paid-up mortgage, and had little to gain by jeopardizing their retirement funds.

With the guidance of legal counsel T. Knox Bell, the La Jolla Cancer Research Foundation (LJCRF) was incorporated in July 1976. On December 1, 1976, the doors of the La Jolla Cancer Research Foundation opened in modest facilities leased from the Scripps Research Institute, 500 sq. ft. in a converted motel, footsteps from the Pacific Ocean.

In Dr. Fishman’s words:

José Luis Millán, Lil Fishman,

Bill Fishman, and early faculty member Cole Manes at first

laboratory, 417 Coast Blvd., La Jolla

La Jolla and the scientific community (have) gained a vital nucleus of scientists devoted to achieving a more precise understanding of the nature and causes of developmental diseases and disorders. The formation of the new Research Center represents an important step into the future. The Foundation, located in an environment where institutions devoted to scientific excellence and facilities involved in fundamental basic clinical research come together, is dedicated to advancing the knowledge of Oncodevelopmental Sciences. [LJCRF brochure, 1977]

As the Institute evolved, Lillian Fishman played the central role in developing community support. For years, she edited the Institute’s newsletter. In the early years, she launched a group of Community Friends who, as volunteers, served as the mainstay for fundraising and social events as well as mailing out the newsletter on a monthly basis. She was integral to building collaborations with neighbors on the Mesa: Salk, Scripps, and the UCSD. Lil remained active in the Institute’s community until the end of her 98-year life, honoring young research scientists with the annual Fishman Fund Awards and hosting a series of educational events.

A typical gathering over lunch at first lab on Coast Blvd. ~ 1977

According to Lillian, the growth strategy focused on recruiting talented young researchers who would become first-class scientists. We invested in young people and gave them the opportunity to develop, she recalled. Our goal was to give them the freedom to do their research, unencumbered by administrative bureaucracy and departmental politics. And this worked.

Dr. Fishman served as trustee, president, administrator, and scientist. He also served as scientific director, until Erkki Ruoslahti, M.D., Ph.D., from the City of Hope in Duarte, California, took over the role in the early 1980s. Dr. Fishman had recruited Dr. Ruoslahti as heir-apparent in 1979. Dr. Eva Engvall, who had invented a leading diagnostic technology, was recruited with Dr. Ruoslahti to pursue her research with an independent appointment and establish her own laboratory. A two-year planning grant from the National Cancer Institute helped the fledgling organization land on its feet—on North Torrey Pines Road. As reported in the LJCRF newsletter, October 1979, my mother’s words:

Through the skillful efforts of trustee Dr. William Drell, we were able to arrange the donation of 4.7 acres of prime land on the Torrey Pines Area of La Jolla from Whittaker Corporation. The land is valued now at over $1,000,000. Another foundation, which must remain unnamed, bought the laboratory buildings and is leasing them to us under a twenty-year renewable lease. …

In a few years, it would be generally known that the unnamed foundation was the California Foundation for Biochemical Research (CFBR), established by Dr. William Drell, founder of Calbiochem. Dr. Drell started CFBR with funds gained through the sale of Calbiochem to Hoescht Corporation to provide scholarships to young students entering the life sciences. He enlisted as Board members the service of long-time friends, distinguished biochemists from Southern California.

Board members, California Foundation for Biochemical Research: Drs. Eugene Roberts (Director, Division of Neurosciences, City of Hope National Medical Center), William Drell (Founder, President/CEO Calbiochem), Donald Visser (USC), Emil Smith (Founder, Molecular Biology Institute, UCLA), and James Bonner (Division of Biology, Caltech)

Dr. Drell, who knew Dr. and Mrs. Fishman socially, took a special interest in Dr. Fishman’s research and was eager to see the fledgling LJCRF succeed. Dr. Eugene Roberts had known the Fishmans for years. Our families summered together in Bar Harbor, Maine, as Dr. Fishman and Dr. Roberts pursued research interests at Jackson Laboratory. CFBR worked with the Whitaker Corporation, the landowner, to make it possible for LJCRF to acquire the land and laboratory buildings on North Torrey Pines Road. This campus would support a growing research program and, long-term, construction of new facilities as the organization expanded.

In 1990, CFBR would donate the buildings to LJCRF, a donation recognized with the establishment of the William R. Drell Chair in Molecular Biology. Dr. John C. Reed would be appointed to the Drell Chair when he joined the Institute in 1992. But we get ahead of ourselves.

The move to North Torrey Pines Road offered existing laboratory space plus acreage for developing new facilities as the organization grew. That Dr. Fishman, and the La Jolla Cancer Research Foundation, could marshal this impressive support from the local community did not escape the notice of Dr. William Terry, representing the National Cancer Institute, at dedication ceremonies for the new facilities on January 18, 1979.

Within six months, on July 1, 1979, Drs. Ruoslahti and Engvall would join the organization. Dr. Ruoslahti would organize a successful program project, which complemented cancer studies already underway and helped to justify Cancer Center status. Within 18 months of the move to the Torrey Pines Research Mesa Campus, in July 1981, LJCRF, under Dr. Fishman’s guidance, would be recognized as a Basic Research Cancer Center by the National Cancer Institute.

Trustee Freddie (Broderick) Deming (Center)

welcomes Dr. Engvall and Dr. Ruoslahti at

Facilities Dedication in January 1979

Effective leadership is the key for any organization that wants to succeed over the long term. The vision and values of the Founders and subsequent leaders create a social DNA that sustains the culture. The leadership skills of Dr. Fishman and Lillian Fishman set the tone for what has developed into the Institute today. While they set the bar—and others have continually raised and improved upon that mark—certain positive characteristics of their organizational culture persist today.

From LJCRF Newsletter, Vol.1, No.1, April 1977

My Philosophy – William H. Fishman

I believe in the team effort and conduct it in such a way that each participant receives full credit for his[her] contributions. Each is encouraged to develop original ideas which can be tested experimentally and subsequently qualify for grant support. Together we have the critical mass of intellects and skills to accelerate progress in oncodevelopmental sciences.

Scenes from the Dedication of North Torrey Pines Facility—January 18, 1979

(From LJCRF newsletter, October 1979)

Dr. Fishman welcomes community leaders and supporters to new campus

The move to North Torrey Pines Road was celebrated in style over two days in January 1979. Day one marked the campus dedication. Three keynote speakers spoke to the Institute’s promise and potential: Dr. William Terry, representing the National Cancer Institute; Dr. Hidematsu Hirai, representing the International Society for Oncodevelopmental Biology and Medicine; and Senator Joseph Biden, representing the public’s interest in funding for medical research. Invited guests were treated to a catered affair, organized and prepared by the recently established Friends of the La Jolla Cancer Research Foundation. The second day was dedicated to a scientific meeting, Perspectives in Oncodevelopmental Biology, the Institute’s first annual symposium.

Dr. William Terry, Acting Associate

Director, Cancer Centers Program,

National Cancer Institute

Dr. Hidematsu Hirai, a founder

of the International Society of

Oncodevelopmental Biology and

Medicine, designates LJCRF as North

American Headquarters for the Society