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Partners in Science

PHILANTHROPY AT WHITEHEAD INSTITUTE 2018

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ContentsDirector’s Letter 1

Accelerating Discovery 4

Fostering the Next Generation of Scientific Leaders 10

Part of an Extraordinary Vision 16

New Ways to Say “Thank You” 18

A True Partner in DiscoveryScientific discovery depends on courageous investigators who push past the present boundaries of knowledge. But not on them alone. An organization like Whitehead Institute also depends on partners who are passionately committed to shaping the future of biomedical research.

A scientific research institution could have no better partner than Arthur Brill, one of Whitehead Institute’s greatest advocates and staunchest supporters. The Institute would not be what it is today without Arthur’s early and longstanding involvement. He was also a dear friend and cherished colleague. When he died suddenly this past June, we grieved deeply. And we will feel his loss, acutely, for a long time to come. But it is impossible not to also feel enormous gratitude for all that Arthur gave us. He has had substantial impact on this institution and, through it, our nation’s scientific enterprise.

Arthur’s role at Whitehead was sui generis: present at its creation — helping Jack White-head write the Institute’s founding documents — and engaged continuously for the next 36 years. He served as secretary of the corporation, a member of the board of directors, and an active part of three board committees. Yet that’s only part of the story. Arthur was fiercely dedicated to scientific research and believed deeply in Whitehead Institute’s mission as an incubator space for basic biomedical science. He loved being part of the research environment and interacting with scientists. He soaked up the intellectual content and was stimulated by the opportunities for learning. Few were the board meetings, scientific seminars, or special events that he missed. And he always engaged whole-heart-edly, with a brilliant intellect and sincere curiosity, a warm smile, and a gentle sense of humor.

Arthur was boundlessly generous — with his time, his knowledge, and his financial support. He and his beloved wife, Carol, had a virtually unbroken three-decade record of philan-thropic gifts. As part of that record, they honored his parents by endowing the Jerome and Florence Brill Graduate Student Fellowship, supporting outstanding graduate students conducting stem cell-related research. They also created the Arthur W. Brill and Carol Tobin Brill Postdoctoral Fellowship for Sex Differences in Health and Disease, supporting young researchers working to discover the role of the X and Y chromosomes in health and disease. They believed that these fellowships would help advance research that could, one day, improve life for all of humanity.

Arthur believed sincerely in Whitehead Institute’s capacity to advance the conduct of science and train coming generations of scientific leaders. Yet he knew that science cannot advance on its own, that it needs partners. For that reason, he communicated this message, far and wide: Today’s medical miracles are based on the kind of work — both painstaking and innovative — done at Whitehead Institute. And he was excited by opportunities for new partners to help shape Whitehead Institute’s next decade of scientific leadership.

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Preparing for that decade, we are enhancing facilities and expanding the faculty, building on the Institute’s pioneering work in fields such as genomics and epigenomics, metabolism, plant biology, RNA function, and regeneration. We continue to build Whitehead Institute’s resource base, preparing it to take on challenges that await just over the horizon. To that end, we are engaging philanthropic partners who want to enhance people’s lives tomorrow by advancing basic biomedical research today.

Many people Arthur introduced to Whitehead Institute became dedicated supporters — providing millions of dollars in funding for research projects, new technology, and the prestigious Whitehead Fellows Program. He was so successful in bringing philanthropists into the Whitehead Institute orbit because he believed that the Institute’s research could change how medicine is practiced. Indeed, for him, it was hard to imagine a better investment.

More than anything else, I am happy and grateful that Arthur chose to invest so much of himself in this organization. We are so much the better for it.

David PageDirector, Whitehead Institute

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Whitehead Institute is preparing to address the challenges of the next 35 years. We are taking the steps necessary to ensure our long-term capacity to imagine, discover, create, and catalyze — in short, we’re preparing to lead biomedical research deep into the “Bio-Century.”

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Accelerating DISCOVERY

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“My hope is that more philanthropists come to recognize the importance of the basic science that Whitehead Institute pursues — and that they will step up to fund research on the biomedical challenges that most engage them.”

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As you might expect of an emeritus dean of the MIT Sloan School of Management, William F. “Bill” Pounds has employed a logical and methodical approach to estate planning. It includes a detailed plan for charitable bequests to the nonprofits most important to Bill and to Helen, his wife of six decades.

“Financially, we feel we’ve accumulated much more than we deserve,” Pounds observes, “and it is important to Helen and me that most of those resources be directed back to the communities of which we’ve been a part. We considered the idea of creating a family foundation but decided that our funds can be best used by advancing the work of organiza-tions that have earned our trust,” Pounds explains. “For that reason, we are leaving the bulk of our resources to organiza-tions, like Whitehead Institute, that we have been engaged with for many years. We created a list of those organizations and assigned each a specific percentage of the funds that will be available. The money will flow to them once Helen and I have both passed on.”

In addition to serving on the Whitehead Institute Board of Directors, now as a director emeritus, Pounds has played a leadership role in iconic Boston institutions, such as the Museum of Fine Arts, the WGBH Educational Foundation, and the Boston Lyric Opera. He and Helen have been generous in their philanthropic support for each of them, and for many other cultural, environmental, and educational organizations — including Massachusetts Institute of Technology and Carnegie Mellon University, where Pounds earned three degrees.

A Legacy of Support for the Whitehead Institute Mission

Pounds’ support for Whitehead Institute has taken many forms: He’s been a prolific donor, providing both regular annual gifts and the more substantial gift that will transfer through his estate. He’s been a “connector,” helping the Institute build new links to the philanthropic, academic, and business communities. And he’s provided Whitehead Institute with wise counsel — sharing expertise gained in his academic career, extensive service on corporate boards, and a long engagement as a senior advisor on financial manage-ment to the Rockefeller family.

Given his deep understanding of organizational management and financing, Pounds generally chooses to make gifts with few strings attached: His annual gifts to Whitehead Institute have been unrestricted in their use, and the bequest gift will be directed to the organization’s endowment. “I will write a letter that offers some thoughts on how the funds might be used. But, in the long term, I believe in Whitehead Institute’s mission, and I trust that its leadership will know better what to do with the money than I,” he says.

“My hope is that more philanthropists come to recognize the importance of the basic science that Whitehead Institute pursues — and that they will step up to fund research on the biomedical challenges that most engage them.”

William F. Pounds

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Whitehead Institute Members Rudolf Jaenisch and Richard Young are both world-class scientists and worldwide adventurers who scale mountains, traverse deserts, and kayak wild waterways. Often they merge the two roles, giving seminars for scientists in the countries they venture through. One such seminar — in Copenhagen in 2015 — led to a series of wide-ranging conversations with scientists at Novo Nordisk, the Denmark-based developer of treatments for chronic conditions including diabetes, obesity, and cardiovas-cular disease.

Those conversations blossomed into a major research program — a series of broadly defined, intersecting basic science projects being undertaken at Whitehead Institute and Massachusetts Institute of Technology (MIT). The projects are underwritten by a multimillion dollar sponsored research agreement from Novo Nordisk over three years. Notably, Novo Nordisk’s support comes with a uniquely open ap-proach to nurturing truly groundbreaking explorations: no mandated transfer of intellectual property or special rights; just the opportunity to enable the research progress and discuss it directly with the researchers.

“I would call this a ‘blue sky’ collaboration,” says Jaenisch, a Whitehead Institute Founding Member and a professor of biology at MIT. “The projects are not completely defined from the outset, and there may not be any patentable intellectual property emerging from our work.”

Underwriting discovery research — investigations not aimed at a specific medical problem — is not typically how pharma-ceutical companies fund research, notes Young, who is also a professor of biology at MIT. “But Novo Nordisk realized that we are exploring important questions in new ways,” he

A Blue Sky CollaborationNovo Nordisk Underwrites Unfettered Exploration

recalls. “They also recognized that we have a pretty good track record of turning up important findings in unexpected places. They’ve further devoted one of their senior diabetes scientists to be based in Cambridge, specifically to provide continuous dialogue so we can jointly spot emergent opportunities we could never predict ahead of time.”

Jaenisch and Young are joined in this powerhouse research collaboration by Linda Griffith, MIT professor of biological engineering and mechanical engineering, and by Nobel laureate Phillip Sharp, MIT Institute Professor, member of the Koch Institute for Integrative Cancer Research at MIT, and member of the Whitehead Institute Board of Directors.

The Novo Nordisk-funded projects will seek fundamental knowledge about, for example, the mechanisms underlying gene regulation and the emergence of disease-causing mutations. But their discoveries could also eventually lead to new approaches to diagnosing and treating a range of diseases. “We share the company’s intellectual interest in diabetes,” Young notes. “The basic functions we are exploring could shed light on interactions that lead, ultimately, to the disease — perhaps helping us understand how a cell’s epigenetics is changed by diabetes, or whether interactions among different tissue types create conditions that allow the disease to develop.”

“This is a situation in which Novo Nordisk and the research-ers share both a genuine passion for the basic science and a long-term perspective,” says Marcus Schindler, Senior Vice President for Global Drug Development at Novo Nordisk. “Supporting the work of these extraordinarily accomplished scientists is one way we are investing in new models of collaboration that can lead to transformational biological and technological innovations in human health.”

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Early in his career, Whitehead Institute Member David Sabatini discovered the mTOR protein. mTOR stands for mechanistic target of rapamycin (an immunosuppressant drug that inhibits cell growth), and the pathway has proven important in cell metabolism. Sabatini’s ongoing efforts to define the mTOR pathway’s effects on cell growth are leading to potential treatments for a range of medical conditions —from tuberous sclerosis complex, which causes autism-like symptoms and benign tumors, to many forms of cancer.

Indeed, because malignancies often grow and proliferate quickly, identifying metabolic vulnerabilities could prove to be an especially productive path to new cancer therapies. Recently, Sabatini’s lab uncovered a potential vulnerability in pancreatic cancer. They have found that the loss of the cellular protein SLC38A9, which helps transport amino acids, severely impairs the proliferation of pancreatic cancer cells in culture and in mice. “The loss of SLC38A9 appears to reduce the availability of specific amino acids that those cells use for fuel,” Sabatini explains. “We’re now investigating exactly why the loss of SLC38A9 has that effect in cancer cells. In parallel, we are screening for compounds with similar effects—which may yield a drug that starves pancreatic tumor cells while leaving normal cells unaffected.”

This pathbreaking study is being underwritten by a three-year, $1 million grant from the Lustgarten Foundation, which was impressed by Sabatini’s record of discovery and by the

Catalyst for Pancreatic Cancer ResearchLustgarten Foundation

promise inherent in his SLC38A9 hypothesis. The largest private funder of pancreatic cancer research, the foundation supports world-class scientists striving to understand the disease’s development and to uncover new treatments.

“We are relentlessly focused on improving patient outcomes by supporting world-class basic and clinical research,” explains the foundation’s president and CEO, Kerri Kaplan. The foundation was created and named in honor of Marc Lustgarten, the late Vice Chairman of Cablevision, Inc. who died of pancreatic cancer in 1999. At that time, pancreatic cancer was considered an orphan disease, and the National Cancer Institute (NCI) spent less than $16.2 million on the disease, supporting fewer than 15 investigators. “Since 1998, the Lustgarten Foundation has made more than $165 million in research awards,” Kaplan notes.

“Those investments have catalyzed the entire field — and the NCI now funds more than $150 million in pancreatic cancer research each year. But our work will not be done until we’ve conquered the disease. David Sabatini’s SLC38A9 study is the kind of intrepid and innovative research that, we believe, will get us to that goal.”

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FOSTERINGthe Next Generation of SCIENTIFIC LEADERS

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A fundamental part of our mission at Whitehead Institute is honing, deepening, and expanding the capabilities of the stellar young scientists who do their graduate or postdoctoral work at the Institute, or who establish their first labs as Whitehead Fellows. By offering world-class mentors, collaborators, and technical facilities, Whitehead Institute helps these researchers pursue courageous science. And when they are ready to take the next step in their careers, these young scientists are recruited by leading universities, research centers, as well as biotech and pharma companies around the world. These are scientists such as Cori Bargmann, an internationally recognized neurobiologist and geneticist, who leads the Chan Zuckerberg Initiative’s science work and is the Torsten N. Wiesel Professor at the Rockefeller University, or former Whitehead Fellows Angelika Amon and Whitehead Institute Member David Bartel, who con-tinue to make tremendous scientific achievements, while serving as men-tors to the next generation of scientists through their work as faculty at the Massachusetts Institute of Technology.

Expanding the resources available to support these emerging scientific leaders is one of the Institute’s top priorities. Federal agencies and foundations provide important funding. But, increasingly, individual philanthropists are stepping forward, and the impact of their support can be incalculable. Here are snapshots of three dynamic young researchers whose work relies heavily on generous donors who are focused on the scientific horizon.

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Postdoctoral researcher Danielle Tomasello has been Whitehead Institute’s Balkin-Markell-Weinberg Fellow — a fellowship established by the late Lorraine Balkin to advance research on brain health at Whitehead Institute. Working with Whitehead Institute Member Hazel Sive, Tomasello studies how metabolic changes in neurons affect disease. She is focusing on 16p11.2 deletion syndrome, in which a piece of chromosome 16 is missing; it is implicated in an array of significant mental health disorders, including autism. In particular, Tomasello is looking at how the lack of one specific gene on the chromosome may alter neuronal metabolism enough to disrupt the cell membrane. That disruption may be key to cellular dysfunctions contributing to serious mental health issues.

The Sive lab primarily uses zebrafish as a tool for observing metabolic changes caused by 16p11.2 deletion syndrome. Tomasello is building on the learnings in zebrafish by developing adult human stem cell lines that can also be used to model metabolic changes and to screen potential therapeutic elements. In this work, she is collaborating with Founding Member Rudolf Jaenisch’s lab, leveraging their pioneering expertise in stem cells to expand the Sive lab’s efforts to understand the metabolic underpinnings of mental health disorders and uncover effective treatments.

“I love doing bench science, but I also want to develop ways to collaborate with clinicians,” Tomasello says. “Being able to engage with the people who have these disorders — and with their families — is both enlighten-ing and a continuing reminder of why this research matters. And I cannot overstate how important the Balkin-Markell-Weinberg Fellowship has been to advancing my work.”

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The Whitehead Fellows Program enables extraordinary young researchers to skip a traditional postdoctoral fellowship working in a senior scientist’s lab, and to undertake their own research plan in a lab they create and manage.

Olivia Corradin holds a Scott Cook and Signe Ostby Fellowship — established by Cook and Ostby to support the emerging leaders selected for the Whitehead Fellows Program. Corradin explores the noncoding sections of the genome — regions of DNA that do not contain genes. There is increasing evidence that these regions may serve a regulatory function that contributes to health and disease, and Corradin is working to determine the functional consequences of DNA sequence variants — small DNA “letter” changes — in certain noncoding regions. Her work has focused on understanding how these variants may contribute to autoimmune disorders, drug addiction, and colon cancer. For example, she is exploring the role played by variants associated with an increased risk for multiple sclerosis (MS), an autoimmune disease that affects the function of myelinating cells in the central nervous system and weakens the brain’s ability to send and receive signals. The causes of MS are poorly understood and treatments are limited in their effects; Corradin’s work has the potential to identify new, more effective ways to approach diagnosis and treatment of the disease.

“One of the major benefits of conducting this research at Whitehead Institute is the opportunity to develop collaborations with world-class scientists, and explore questions that had not even been on my radar screen before,” Corradin observes. “For example, we’ve begun working with the Sive lab, applying knowledge and techniques our lab developed in studying noncoding variants, to further expand their investigations of the drivers of metabolic changes seen in 16.p11.2 deletion syndrome.

“In that respect, not only has the Scott Cook and Signe Ostby Fellowship been instrumental to my lab’s work, it has enabled us to develop partnerships that leverage our core efforts and discoveries in exciting ways.”

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Silvi Rouskin is the Andria S. and Paul G. Heafy Whitehead Fellow — a fellowship established by the Heafys to support pioneering young researchers in the Whitehead Fellows Program. Rouskin studies RNA structure and its implications for health and disease. Beyond its role in translating the information in DNA into proteins, RNA can fold into struc-tures that, themselves, interact with other molecules or catalyze biochemical reactions in the cell. Rouskin is looking specifically at the structures of messenger RNA (mRNA), which are critical for embryonic development and normal cellular function. By learning the principles guiding mRNA folding, she hopes to better understand how RNA structure regulates normal cell activity and what specific aspects may go awry and cause disease.

To date, the tools that allow scientists to discern an RNA’s shape have been quite limited, compared to those available for analyzing protein structure. But Rouskin is changing that status quo: She has introduced an algorithmic approach that takes data from a chemical probe of a cell’s RNA and identifies the multiple structures that a given sequence of RNA could form. Her tool makes it far easier for researchers to study RNA folding, enabling them, for example, to recog-nize connections between folding patterns and diseases, such as cancer and neurodegenerative conditions. Her lab has used the tool to determine that the RNA of human immuno-deficiency virus (HIV) commonly forms multiple structures; they are now investigating how these different structures regulate gene expression.

“I am really pleased that — through the tools we are creating and the scientific discoveries we’re making — we are able to give Andria and Paul Heafy a substantial scientific return for their philanthropic investment in early-career researchers,” Rouskin says.

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Part of an

Extraordinary Vision

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Whitehead Institute was born of two extraordinary philanthropic acts, Edwin C. “Jack” Whitehead’s gifts to launch the Institute and, subsequently, to create its core endowment. Jack’s gifts were such an anomaly during their day that he reported being hounded by the media. The public wanted to know why he had made such large gifts to biomedical research. When he explained that it was pure philanthropy and not a business investment, people struggled to comprehend. A philanthropic visionary, he understood the tremendous impact that his philanthropy could have, decades before transformational gifts became common in our world. His concept was revolutionary: Support an idea that has the potential to vastly improve the lives of humankind — now and for future generations — and invite others to be a part of this vision.

Over the years, Whitehead Institute has benefitted from the generosity of donors whose contributions, large and small, have enabled us to grow. They have brought more than their philanthropic support to the table: They have served as ambassadors, enlarging our circle by introducing us to other like-minded individuals. They have also been bridge-builders, and idea-generators. Their ideas have seeded initiatives and new entities at the Institute, such as the creation of our intellectual property office — the brainchild of the late Landon Clay. Or the childcare center, a critically important part of enabling a strong work/life balance for our investigators, which was championed by Brit d’Arbeloff.

As David Page expressed in his letter, our dear friend Arthur Brill performed this role with passion and consummate skill, working with us to make sure that science was well-support-ed, promoted, and showcased. He truly wore the mantle of Whitehead Institute ambassador, and he took Jack Whitehead’s vision forward — as do all of our donors and friends — by bringing new science-lovers into the fold. We are thankful to our many friends in New England, New York City, and across the United States, who work diligently to forge new connections for Whitehead Institute with individuals and organizations who wish to learn about the Institute’s tremendous record of accomplishment. This is the Whitehead Institute community, and it is expanding every day.

Sincere thanks to our community for being a part of what continues to be a game-changing vision, supporting the important work of scientists who are driving the frontiers of discovery forward for the benefit of humanity.

With great gratitude,

Sharon J. Stanczak

Vice President for Institutional Advancement Whitehead Institute

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Whitehead Institute’s Giving Societies honor our most philanthropic donors — a diverse community of individuals, families, corporations, foundations, and organizations who have contributed $250,000 or more. These recognition societies will enable us to provide each member with individualized stewardship and engagement. (All former Board of Associates members have been inducted into the society that reflects their level of lifetime giving.)

Kendall Square Pioneer Society Named for Whitehead Institute’s role as a pioneering biomedical research institution located at the epicenter of Kendall Square, the Society recognizes donors whose lifetime commitment to Whitehead Institute rests between $250,000 and $999,999.

David Baltimore Society Named for the first director of Whitehead Institute — the Nobel Prize winning biologist and California Institute of Technology President Emeritus David Baltimore — the Society recognizes donors whose lifetime philanthropic commitment to Whitehead Institute rests between $1,000,000 and $4,999,999.

Jack Whitehead Society Named for the visionary industrialist, philanthropist, and founder of Whitehead Institute, the Society honors donors whose lifetime philanthropic commitment to the Institute has reached or exceeded $5,000,000.

Director’s Circle In recognition and celebration of our committed donors who generously make annual gifts of $2,500 or more for three consecutive years, the Director’s Circle has been established.

For more information on these societies or on the Director’s Circle for Annual Fund donors, please contact Erin DeMarco at edemarco@wi.mit.edu or 617.324.4923.

New Ways to Say “Thank you”

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CreditsDirector and Editor Lisa GirardWriters Greta Friar, Merrill Meadow, Nicole Giese Rura

Photography Whitehead Institute Members, Fellows, administration: Gretchen Ertl

Microscopy Front cover, back cover, and page 18: Lauren CoteInside front cover: Mina KojimaPage 3: Marine KrzischPage 6: Nicki Watson

Illustration Steven LeeDesign Subbiah Design

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