Inside Salk; Salk Institute

Private philanthropy redraws the landscape of Salk science

Cell

Hu Cang (center) and Quan Zhu (right) have developed a method for imaging how DNA bundles inside a cell's nucleus. Ying Hu (left), a postdoctoral researcher in Cang's lab, also contributed to the research.

Visionary donors have long recognized the unique character of the Salk Institute and come forward with contributions, large and small, to advance its mission of discovery. With their generous support, the Institute attracts the best scientific minds in the world to work in open collaboration, conducting innovative research, making discoveries and mapping the blueprints to enable cures to be developed anywhere.

It is this generosity—and the environment it creates—that brought together Quan Zhu and Hu Cang to work on a bold new idea.

When Zhu, a molecular biologist, wanted to see how cancer cells interpret genetic instructions, she turned to Cang, a physicist. Combining their expertise in two very different fields, the two Salk scientists are using microscopes to visualize in unprecedented detail how DNA in living cells is bundled inside the nucleus. They are helping to explain how genetic regulation in cancer cells and stem cells is different than it is in other cells—research essential to developing new regenerative medicine and cancer therapies.

"This has bridged a chasm in studying how our genome is regulated," says Zhu, a research associate in the lab of Inder Verma, a professor in the Laboratory of Genetics. "If you can see with your own eyes, you can learn things that aren't otherwise possible."

Since the Salk Institute's inception in the 1960s with a landmark gift from the March of Dimes, the generosity of those who believe in Salk has supported the Institute's ambitious research. Today that spirit of giving is more critical than ever. Zhu and Cang's success is a testament to the growing importance of private philanthropy in supporting the kind of groundbreaking biomedical research for which the Salk Institute is known. Their work is drawing on the resources available in the Waitt Advanced Biophotonics Center, a cutting-edge microscopy center established at Salk with a $20 million gift from Ted Waitt, Vice Chair of Salk's board of trustees. In fact, Cang joined the Salk faculty in large part because of the biophotonics center.

"Already I've seen remarkable discoveries emerging from that investment—findings that are changing our understanding of life and disease." -Ted Waitt, Salk Trustee

Waitt's generous support and that of other philanthropists has been crucial in allowing Salk to capitalize on powerful new imaging technologies, methods for measuring chemical changes and genetic activity in cells, and computational methods for analyzing the massive amount of data these approaches produce. These remarkable advances are proceeding against a backdrop of declining federal funding for basic biomedical research, making private philanthropy essential to developing new therapies against a range of diseases.

Martin Hetzer and Ted Waitt

Martin Hetzer (left) heads the Waitt Advanced Biophotonics Center, which was launched with a gift from Ted Waitt (right).

By all accounts, the biophotonics center has transformed how science is done at Salk. Three sought-after new faculty members, including Cang, have joined the center since it opened in early 2011. "Biology has become an extremely interdisciplinary field, and the center has allowed us to recruit people with bioengineering and biophysics backgrounds that we couldn't have otherwise attracted," says Martin Hetzer, a Salk professor and director of the center.

The center's core facility is equipped with some of the most advanced imaging and microscopy instrumentation in the country. More than 40 Salk laboratories use the facility, with about 300 Salk researchers using the imaging equipment on a daily basis. So far, at least 15 high-impact research papers by Salk scientists have resulted from experiments that relied on the facility's expertise and equipment.

Waitt, who founded Gateway, Inc., and has gone on to form multiple enterprises since his retirement from the company, has been gratified by the results of supporting the biophotonics center.

"Science, like technology, is always changing and advancing," he says. "I wanted to give Salk's phenomenal scientists the tools they needed to take advantage of these new imaging technologies to take their science one step further. Already I've seen remarkable discoveries emerging from that investment—findings that are changing our understanding of life and disease."

Verma, who helped establish the biophotonics center, credits its success in large part to Waitt's involvement in determining early on what technologies and expertise were most needed. "It was really a joint effort," Verma says. "Ted really understood the power of the technology, but he also actively participated in building the center. He continuously pushed us to get it right."

Verma also cites gifts by Irwin Jacobs, chairman of Salk's board, and his wife, Joan, as examples of philanthropic giving that have made a big difference at Salk. Among other generous investments in Salk science, the Jacobses created a challenge grant to encourage donors to establish edowed chairs for senior scientists at Salk. For every $2 million that a donor contributes toward a chair, Joan and Irwin Jacobs add $1 million to achieve the $3 million required to fully endow the chair . To date, 15 chairs have been established.

"Salk's highly talented cadre of scientists continues to make important contributions to our understanding of biology and disease," Irwin Jacobs says. "Joan and I are deeply impressed by the commitment, creativity and passion they bring to the discovery process, and we are proud to support their work."

"Generous gifts from individuals and foundations have continued to provide the margin of excellence for the Salk. By supporting risk-taking and innovation, philanthropy enables Salk scientists to do what they do best—make the high-impact discoveries that lay the groundwork for new therapies and cures." -Marsha Chandler, Executive Vice President, Salk Institute

The Jacobses, along with many other private donors, have also given generously to Salk's Innovation Grants Program, a fund that supports promising studies that would have difficulty garnering federal funding, which favors more established traditional lines of research. By helping researchers establish proof-of-concept data, the program allows them to then leverage outside support to expand on the studies.

"Federal funding has traditionally provided the lion's share of funding for research that has improved medicine with each generation, but that support is declining," says Salk president William R. Brody.

Since the 1960s, funding for basic science in the United States has dropped from approximately 1.9 percent of the gross domestic product to around 0.7 percent, less than half that of the peak. Since 2003, the National Institutes of Health budget has declined in constant dollars—with the exception of the two-year American Recovery and Reinvestment Act, which has now expired.

"The success of Salk and other biomedical research institutions will rely more and more upon private individuals and foundations with the foresight to understand the impact their giving has on this critical work," Brody says.

Fortunately, as the need is growing, so too is giving. From 2003 to 2012, philanthropic contributions to the Salk grew annually from $19.8 million to $50 million, a 150 percent increase in less than ten years. This unprecedented growth has helped the Institute hire and retain top-notch faculty, postdoctoral researchers and staff; acquire new research technologies; and fund innovative experiments.

Rebecca Newman, Salk's vice president, external relations, credits this success in part to growing awareness among donors of the importance of basic biological research in laying the groundwork for cures to diseases and other human health issues. Building strong development and communications teams at Salk, she says, has proved crucial to attracting increased support for the Institute's work.

"We've been much bolder in explaining the importance of Salk science as the bedrock for clinical science," she says. "Clinicians will tell you that they can't do their work at the patient's bedside without the work done at the Salk. Our donors understand that they are supporting the first, indispensable step in this process of discovery and its impact on human health."

"I think any way that you can further science you, in effect, change the world." -Elizabeth Keadle, Salk Donor

This sentiment is echoed by Elizabeth Keadle, a loyal donor to Salk who once worked in the laboratory of the late Salk professor Wylie Vale. She continued to follow the work of Vale's laboratory over the years and has been particularly intrigued by the Institute's research in plant biology, neuroscience and metabolism.

"I think any way that you can further science you, in effect, change the world," Keadle says. "Very few of us have the abilities that the scientists at Salk possess. Supporting them is an honor and an opportunity to be a small part of their amazing work."

Ronald Evans, a professor in Salk's Gene Expression Laboratory, says philanthropic support has funded creative, high-risk projects at Salk that wouldn't have received federal government funding.

Evans is a member of the Salk Center for Nutritional Genomics, which was established in 2009 with a $5.5 million grant from the Leona M. and Harry B. Helmsley Charitable Trust. The center employs a molecular approach to nutrition and the role of metabolism in diabetes, obesity, cancer, exercise physiology and lifespan, thereby expanding our understanding of how nutrients affect health. It includes a metabolic core facility and an interdisciplinary fellows program.

The center has allowed Evans to work closely with two other Salk professors, Marc Montminy and Reuben Shaw, by providing them with research technologies that bridge their areas of expertise. Together, the trio has made key discoveries regarding genetic switches that potentially point to new ways of controlling the body's production of glucose, the simple sugar that is the source of energy in human cells and the central player in diabetes.

"We want to understand what's happening at the genetic level and how this leads to changes in physiology and disease," says Evans. "The center allows experts in cellular genetics and genomics to team up with experts in the physiology of disease. Federal funding mechanisms support projects that remain squarely in one of these areas, but not the kind of cross-disciplinary research we're undertaking in the center."

The initial Helmsley Trust grant was followed in 2010 with a $15 million grant to create a collaborative stem cell project involving Salk and Columbia University. This program was designed to fast-track the use of induced pluripotent stem cells to gain new insight into disease mechanisms and screen for novel therapeutic drugs. The funding helps Salk's Stem Cell Core facility support over 15 laboratories working on regenerative medicine.

John Codey, a trustee for the Helmsley Trust, said his organization is proud of its long and successful partnership with the Salk Institute.

"Our philanthropic investment has produced tangible and impactful results, and we have forged lasting friendships with Salk researchers and staff members." -John Codey, Leona M. and Harry B. Helmsley Trust

He adds that the trust has supported Salk research because basic research is the foundation for cures for devastating diseases like cancer and metabolic and neurodegenerative disorders.

"Our philanthropic investment has produced tangible and impactful results, and we have forged lasting friendships with Salk researchers and staff members," Codey says. "The Helmsley Trust's philanthropy has helped plant the seeds that will grow and develop into clinical treatments and cures, and we look forward to many more years of partnering with Salk to improve human health."

Just as the Helmsley Trust support made the collaboration between Evans, Montminy and Shaw possible, the Waitt Center for Advanced Biophotonics paired the unlikely team of Hu Cang and Quan Zhu—the physicist and molecular biologist working together to develop a powerful imaging technique.

Their work is providing the sharpest live-cell images ever taken of chromatin, the combination of proteins and DNA that form bundles in a cell's nucleus. Chromatin plays a key role in determining which genes in a cell are expressed, and understanding the chemical modifications to chromatin that control this process is the basis of a hot new field known as "epigenetics." The ability to visualize chromatin bundles in high resolution in living cells is allowing Zhu and Cang to map how epigenetic changes alter cellular function. Imaging chromatin structure might even be used to identify cellular pathologies in the same way a pathologist currently uses the shape of a cell nucleus to diagnose a disease.

Ultimately, Zhu and Cang's work is nourished by the same wellspring of generosity and vision that helped launch the Institute a half-century ago and that will allow inspired science to thrive well into the future. "If it wasn't for private philanthropy, I couldn't have come to the Salk and had this close relationship with biologists," Cang says. "This is a great place for pushing engineering into biology in a way that really makes a difference, and that's only the case because of the vision and generosity of a private donor."