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Monday, July 14, 2014

Science Breakthroughs The Koyal Group InfoMag News: Discovery Science Powered, Increasingly, by Donors

As co-director of the Harvard Stem Cell Institute, David Scadden hopes to inspire his students to join the ranks of researchers who might one day cure Parkinson’s or Alzheimer’s or diabetes. But all too often these days, he is losing out to Wall Street, or other higher-paying pursuits.

“They are seeing their senior mentors spending more and more time writing grants and going hat in hand,” Scadden said, in a phone interview. “That’s not a good way to inspire the best and brightest.”

It is an empirical fact that there’s now far less money going toward research science than there used to be, due first and foremost to the decrease in government spending on such research. The budget of the National Institutes of Health is lower (in inflation-adjusted dollars) that at any point since 2000, and 22 percent lower than it was in 2003.

This has meant that the former star students who chose to spend their lives in a lab, working with stem cells or sequencing genomes, the kind of work that most experts believe will usher in the next great medical revolution, are more reliant than ever on a handful of Americans to fund basic research.

That source of funding, while vital, is unstable and relatively scarce.

“We’re going to lose a generation of young scientists, and that’s not something you can make up,” said Dr. Laurie Glimcher, Dean of Weill Cornell Medical College.

Traditionally, researchers rely on a three-legged stool for funding.

While one leg is made up of government grants, another is made up of industry, which pays scientists to research treatments that can be the next billion-dollar idea. But when it comes to discovery science, whose outcomes are inherently unpredictable and which is often conducted without targeting a specific disease, industry tends to be risk-averse.

That leaves philanthropy.

Fiona Murray, a professor of entrepreneurship at M.I.T., published a paper in 2012 finding that philanthropy, both private and corporate, provides almost 30 percent of the annual research funds for leading universities. She also found that while federal funds have been declining, philanthropic funds have been increasing.

“The role of science philanthropy—gifts from wealthy individuals, grants from private foundations to scientific research, and endowment income earmarked for research—is an underappreciated aspect of philanthropy in higher education whose importance becomes clear by examining trends in funding university research,” Murray wrote. “Industry contributions (usually regarded as the alternative funding stream for university research) amount to less than 6 percent of university research funding. In striking contrast, science philanthropy makes up almost 30 percent of university research funding and has been growing at almost 5 percent annually.”

It’s that funding that has made possible a series of breakthroughs that could have outsize clinical implications during the next few decades.

On the west side of harlem, in an unadorned building, some of the most exciting research in medicine is taking place, and almost all of it is being paid for by private donors.

The New York Stem Cell Foundation is supported in part through the Druckenmiller Foundation. The stem cell foundation’s fellowship program is the largest dedicated stem cell fellowship program in the world, and they are one of the only two labs in the country working successfully on a procedure known somatic cell nuclear transfer.

Remember Dolly the sheep? It’s that kind of science, but a bit further along, and instead of cloning mammals, scientists work to create cells, organs or tissues that can replace diseased cells in the human body.

The federal government, for political and ethical reasons, won’t fund any of it.

Though President Obama reversed the Bush administration’s position on funding stem cell research, no new embryonic stem cell lines can be supported because of something called the Dickey-Wicker Amendment, which is renewed every year and prohibits federal funding for synthesizing new stem cell lines. (The Obama administration allows N.I.H. funding for research on new lines that were created with private dollars.)

“It’s really an illusion that the government has both feet in,” said Susan Solomon, C.E.O. of New York’s Stem Cell Foundation. “Without philanthropy we would not have a single stem cell research program in this country.”

This past April, a team of scientists from the foundation created the first disease-specific embryonic stem cell line with two sets of chromosomes.

That means researchers were able to create patient-specific stem cells from an adult human with type 1 diabetes that can give rise to the cells lost in the disease, according to Dr. Dieter Egli, who led the research and conducted many of the experiments.

The stem cell experiments began at Harvard and the skin biopsies were done at Columbia. But isolation of the cell nuclei from these skin biopsies couldn’t be conducted in the federally funded laboratories at Columbia, and Harvard scientists had to stop research in 2008 because restrictions in Massachusetts prevented them from obtaining human eggs for research.

Stem cell science is one of the most conspicuous areas of research in which philanthropy is being asked to pick up the slack left by receding public investment. And in the specific case of stem cell research, donors have stepped in to make up the lack of public money.

But overall, money for research is way down, reflecting a general aversion by both the public and private sectors to fund medical-science projects without likely short-term rewards.

“As resources have shrunk, the ability to tolerate risk on bold ideas of course decreases,” Scadden said. “There is an increased attention to ‘what’s the payoff, what’s the return on investment? Can you show me a direct link to the way my constituents benefit?’”

The problem is that science, generally speaking, doesn’t work like that. Telomeres, the tips of chromosomes that protect DNA during cell replication, were discovered in the 1930s. No one knew what they did or if they were of practical importance. Today, scientists think they might hold the key to battling tumor development.

“Today’s medical miracles are yesterday’s wild ideas in a basic laboratory,” Scadden said.

Donations to stem cell work aren’t much different in that respect from the $12.5 million donation by former Microsoft C.T.O. Nathan Myhrvold for a telescope that will search for extraterrestrial life. Scientists haven’t found any yet, and may never, but that shouldn’t be the point.

“While it’s impossible to predict exactly what we will find with a new scientific instrument, we should remember that interesting science is not just about the likelihood of end results—it is also about the serendipity that occurs along the way,” Myhrvold said in 2000 when donating the money.

Last year, the American Association for the Advancement of Science began a coalition of funders that aims to double philanthropic support for basic science over the next five years.

“The concern of this group is that there is such a big push on the translation science at the expense of the discovery science, which is essentially feed-corn,” said Vicki Chandler, chief program officer for science at the Gordon and Betty Moore Foundation in California, one of several foundations that joined the coalition. “And if we keep heading [toward] that balance there may not be as many as great things to translate from in the next decade.”

Despite the changing proportions of money for research, the United States government remains the principal lifeline for science. The N.I.H. budget is just under $30 billion, much of which is invested in research grants. Private funding for basic research, the kind that doesn’t attach itself to a specific disease or therapy—is only somewhere between $2 and $4 billion.

The question is how far or fast the balance between public and private funding is shifting, and where it will end.

The more it shifts, the more research scientists are coming to rely on a select few donors, who can drive the agenda.

T. Denny Sanford, for example, donated $100 million last year to the creation of the Sanford Stem Cell Clinical Center at the University of California, San Diego.

“I believe we’re on the cusp of turning years of hard-earned knowledge into actual treatments for real people in need,” Sanford said last November. “I want this gift to push that reality faster and farther.”

In 2012, Mort Zuckerman pledged $200 million for the Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia University.

The Ansary Stem Cell Institute at Weill Cornell exists because of $15 million donation from Shahla and Hushang Ansary, the major Republican donor and former Iranian diplomat.

But Murray, the M.I.T. professor, found these examples are more exception than rule. Her research found “little support” for the notion that philanthropists fill gaps left by federal funding.

“In addition,” she wrote, “few philanthropists appear to seek to identify such gaps. This fact is underscored by one key fact about philanthropy: philanthropists are more concentrated in their giving to specific (translational) fields than the government, suggesting that with few exceptions … patrons add support to already well-funded wealthy fields instead of filling gaps.”

That’s frustrating, Glimcher said, because scientific research seems so close to potentially important breakthroughs on so many medically significant fronts.

Given new tools for genetic sequencing and a better understanding of chemistry, basic discoveries can yield clinical trials faster than ever before. But not if that basic science isn’t funded.

“It’s frustrating right now because we are at a time when we can translate basic discoveries into new therapies for patients,” Glimcher said. “Philanthropic research can be a temporary stop-gap and a wonderful addition to reduce the sting of cuts in government funding, and it can top off government funding, but it’s never going to replace government.”

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