Needed: a quantum leap

Bill Snyder
Published: January, 2009

Illustration by Antonello Silverini
One of the great transformational moments in biomedical science is happening right now.

It’s the shift from gene to cell.

“I think what we’re seeing in this century now is a renewed appreciation for not DNA… but cells as being the secret to life,” says Harvard stem cell researcher Douglas Melton, Ph.D.  “We’ll see what I might call a more synthetic biology, using information obtained from DNA to think about how cells work, about physiology and how our bodies work.”

Richard Caprioli, Ph.D., who directs Vanderbilt’s Mass Spectrometry Research Center, thinks a lot about the cell, too. But for him, it’s metaphorical.

“I don’t think we as scientists are really going to make huge innovations in understanding until we integrate just like the cell does,” Caprioli says.

Richard Caprioli, Ph.D., director, Mass Spectrometry Research Center
Photo by Joe Howell
Some of U.S. science today is “too highly focused,” he says. “We all have our own expertise, jargon and acronyms generally not understood by non-experts in a particular field. We need to work much closer together to achieve a quantum leap from where we are.”

This transformation must include the entire scientific enterprise, Caprioli asserts, from the university research lab to the National Institutes of Health (NIH) and even to industry.

Lens magazine asked Caprioli and other scientists at Vanderbilt and throughout the country to brainstorm ideas for revitalizing the nation’s biomedical research enterprise.

Their suggestions may surprise you.

Stop yo-yo funding

Continued support of the NIH is essential, but simply increasing its budget will not solve the problems facing U.S. science. What’s needed instead is stable funding, a budget that does not wobble up and down in response to the vagaries of the political system.

Scott Hiebert, Ph.D., professor of Biochemistry
Photo by Joe Howell
“The budget of the NIH should not be an annual legislated amount of money,” argues Jeff Balser, M.D., Ph.D., dean of the Vanderbilt University School of Medicine and associate vice chancellor for Health Affairs. Instead, it should have a “fixed adjusted-for-inflation increase over a 10-or-so-year period like many programs in government.”

If the National Cancer Institute, for example, “knew what its budget was going to be five years from now, imagine how effective and efficient they could be in planning programs,” he says.

Yo-yoing funding is not only a problem for NIH, it can be crushing to the individual investigator, and it ends up wasting tax dollars, adds Scott Hiebert, Ph.D., associate director for basic science programs at the Vanderbilt-Ingram Cancer Center.

“The vast majority of researchers across the country have one or two grants, and when their grant doesn’t get renewed for two cycles the research stops, and then it gets funded and they have nobody in the lab to do it,” Hiebert says.

“It takes a couple of years to get going. And we’re doing this and it’s killing us. We’re wasting tax dollars doing this because we’re losing the momentum.”

Dan Masys, M.D., chair, Department of Biomedical Informatics
Photo by Joe Howell
“This thing of going up a lot and then going down a lot is just devastating to the continuity of laboratories (that) are trying to… make a breakthrough,” agrees Heidi Hamm, Ph.D., chair of Vanderbilt’s Department of Pharmacology. “You lose trained people in your laboratory. You start all over. It’s a wasteful system.”

Funding a program is not unlike flying a plane, adds Dan Masys, M.D., chair of Biomedical Informatics at Vanderbilt and a licensed pilot. Repeatedly climbing and descending instead of keeping to a steady altitude can increase fuel consumption by 60 percent while actually lengthening the time to reach a destination, Masys says.

Partner with industry

Academic medical centers also need to be innovative in their acquisition and use of research dollars, Vanderbilt scientists say.

One of the reasons that Vanderbilt Medical Center has had a successful research enterprise is that it has invested in “elements of 21st century success,” Masys continues. These include information technology and other systems approaches aimed at squeezing waste and inefficiency out of its delivery of health care, while improving quality and outcomes.

“It’s vision; it’s core facilities; it’s a lot of different strategic moves we’ve made over the years,” adds Mark Magnuson, M.D., who directs the Vanderbilt Center for Stem Cell Biology.

Another avenue of innovation can be found in collaborations with industry.

Jeffrey Conn, Ph.D., director, Program in Drug Discovery
Photo by Joe Howell
“We’re in the place in our biomedical research history and the history of the pharmaceutical industry especially where companies are desperate for new models and opportunities to invest,” says Jeffrey Conn, Ph.D., director of the Vanderbilt Program in Drug Discovery.

Drug companies are reluctant to invest in university-based research “for the sake of research,” Conn says, “but when they see research that can impact the company’s viability, those opportunities are there.”

An example is Vanderbilt’s partnership with the Boston-based biotech firm Seaside Therapeutics to find potential treatments for fragile X syndrome, the most common inherited form of mental retardation and the most common genetic cause of autism. The goal is to reduce or eliminate the neurological and psychiatric consequences of the condition by chemically modulating the aberrant signaling of a neurotransmitter in the brain.

“If it works, it could be transformative,” says Conn, who led the neuroscience program at Merck for several years. “It could totally change the way people view developmental disorders.”

As academic medical centers do a better job matching their needs with those of pharmaceutical companies, he continues, “I think we increase the productivity of the companies that rely on (that) science… and then we increase the support of the public. The reason that we’re having such a crisis right now with public support is that they see this investment, and they’re looking for what’s coming out of it.”

Diversify research support

Innovation also must extend to the pursuit of a diverse portfolio of research support.

Toward that end, Vanderbilt Medical Center has created a program focused on helping investigators find the support that they need. Many of these foundations “have a strong interest in developing the careers of junior faculty members, coupled with a mission to fund basic, translational and clinical research,” says Vanderbilt’s director of Development for Biomedical Research, Julie Koh, Ph.D.

Julie Koh, Ph.D., director of Development for Biomedical Research
Photo by Joe Howell
For example, the Howard Hughes Medical Institute (HHMI) recently created 70 Early Career Scientist positions as an investment for the future. The institute also is granting new funds through its newly established Collaborative Innovator Award project. Here the principal investigator (PI) must be an HHMI researcher, but the research team must include others from outside his or her discipline, from outside the institute or even from outside the United States.

Says Jack Dixon, Ph.D., HHMI’s chief scientific officer and former dean for Scientific Affairs at the University of California, San Diego: “The strategy is to develop teams of people to tackle important problems that couldn’t be tackled as effectively by an individual laboratory. It’s something of an experiment for us.”

Grassroots movements like ACT-UP, which promotes AIDS research, and private foundations like the Michael J. Fox Foundation for Parkinson’s Research, which supports research and drug development, are among the increasingly powerful funders of biomedical research.

The recently formed Stand Up to Cancer, which raised more than $100 million during a televised celebrity fundraising event last fall, directs its donations to “interdisciplinary, multi-institutional translational and clinical research Dream Teams” in order to speed progress and “achieve a paradigm shift in clinical cancer research,” according to its Web site, www.standup2cancer.org.

Similarly, the Multiple Myeloma Research Foundation has used a “pay-for-results” funding model that, in the words of TIME Magazine’s Bill Saporito, “has more to do with Silicon Valley than Big Pharma.”

Foundations also can provide “support for controversial or unpopular topics where government is reluctant to tread, and nurturing of ideas early in their inception prior to broader acceptance,” said Susan Fitzpatrick, Ph.D., vice president of the St. Louis-based James S. McDonnell Foundation.

“Having a large number of funding organizations with diverse decision-makers helps ensure flourishing of alternative models and approaches that may depart from the common wisdom or challenge the status quo,” Fitzpatrick said in remarks prepared for a forum on science and technology policy hosted by the American Association for the Advancement of Science last May.

“Driving cures requires investing in high-risk science,” adds Brian Fiske, Ph.D., an associate director of research programs at the Michael J. Fox Foundation, which committed more than $30 million in new Parkinson’s disease research in 2008. “It’s all about testing hypotheses that may very well fail, and betting on technologies that may fall apart or become obsolete in a few years. But if we don’t take that risk, others won’t.”

The foundation is currently funding clinical trials of several novel therapeutic approaches to Parkinson’s disease that otherwise would likely not yet have advanced to testing in patients.

“When the foundation was launched in 2000, we didn’t necessarily anticipate that we would have to go this far before someone else would take the lead,” Fiske says. “But we can’t stand by as potentially promising drugs sit on the shelf and never go to definitive clinical trials, and no one ever knows if they will work or not.”

Private efforts, however, do not come close to matching the $28-billion-a-year NIH “engine” that drives the nation’s biomedical discovery enterprise. Notes Conn: “I think the entire system would implode if you didn’t have that strong national investment.”

Invest in education

Nurturing the spirit of discovery ultimately must begin with the next generation.

That’s why an increasing number of scientists and universities around the country are partnering with public schools to bring more of the joy and excitement of discovery into the classroom. VUMC, for example, has provided summer science workshops for teachers for more than a decade.

“These science teachers out there are highly motivated. They just need… access to mentoring from us,” Balser says. “And so creating a really direct linkage between the science teachers in this community and university faculty so that we’re all part of a community, and we’re all engaged in this together—that’s really where the solution lies.”

Individual faculty members and students from Vanderbilt also are investing their time and talents to help capture the imagination and talent of public school students.

Last year, for example, Vanderbilt Student Volunteers in Science, a 15-year-old organization of undergraduate, graduate and medical students, brought hands-on science lessons to more than 120 middle school classrooms in Nashville.

Wonder Drake, M.D., assistant professor of Medicine
Photo by Joe Howell
In 2007, Billy Hudson, Ph.D., director of the Vanderbilt Center for Matrix Biology, launched the “Aspirnaut Initiative” to provide laptop computers to middle and high school students in rural Arkansas, where he grew up, so they can access accelerated math and science programs during long bus rides to and from school.

Wonder Drake, M.D., assistant professor of Medicine, brings young people from her church into her lab for summer research experiences. Some of them were at risk of being turned off by school. But the lab experience challenged them.

“We mentored 10 kids over a five-year period in my lab, and six of (them) are in graduate school right now, either an M.D., Ph.D., or M.D./Ph.D. program,” she says. “One reason for their success is that they found translational research very exciting; it provided them an opportunity to see how stimulating the life of a scientist can be.”

Improving science education also benefits the broader society, argues Bruce Alberts, Ph.D., former president of the National Academy of Sciences and current editor-in-chief of the journal Science.

“If we made the kind of investments in teacher education and teacher support that we need to make as a nation, we could create a citizenry that would be much more effective in the workforce, because those people would be able to solve problems on the assembly line and in the workplace,” Alberts maintains.

That’s important, he adds, because in order for the United States to thrive amidst the challenges of the 21st century, its citizens “need to be problem-solvers. They need to be independent thinkers. They need to see how to fix things that are wrong, and then move forward.”

Sell the story

Given the global financial crisis, it will not be easy to increase support of research and education.

One possible solution: health care reform.

Peter Buerhaus, Ph.D., R.N., Institute for Medicine and Public Health
Photo by Joe Howell
According to Peter Buerhaus, Ph.D., RN, an expert on health care workforce issues in the Vanderbilt Institute for Medicine and Public Health, our nation’s health care delivery system wastes 30 cents of every dollar—about $700 billion a year. “That’s 20 times the NIH budget,” he points out.

“Something we can all agree on is to get rid of the waste and inefficiency in the delivery system that results in nothing,” Buerhaus continues. “It’s not as if we have to create a lot of extra dollars (to support research). It’s just that we need to put some discipline into this crazy system that is going to get way out of control as we move forward with these 80 million Baby Boomers” who are entering their retirement years.

William Lawson, M.D., assistant professor of Medicine at Vanderbilt who has advocated nationally for more federal funding for research, notes that the nation spends between $6,000 and $7,000 per year on health care for each of its 300 million citizens, but “less than $100 per person” each year for NIH-sponsored extramural medical research. “That’s a huge gap,” he says.

And while health care reform has been a political “third rail,” electrocuting all who come near, it is equally true that scientists have failed to sell the story of biomedical research in a clear and consistent manner.

Douglas Melton, Ph.D., co-director of the Harvard Stem Cell Institute
Photo by Dana Johnson
“Information is the most important thing in clarifying… misimpressions and/or wrong-headed thinking about things,” says Harvard’s Melton, who is studying how cells might be reprogrammed to cure type 1 diabetes.If you look in the political arena, it’s usually the way words are twisted or there’s seeding purposefully of misinformation that leads people… to the wrong opinion.”

For example, to scientists the word “cloning” means making copies of DNA or cells. But “to my neighbor it means making copies of people, and I don’t know any scientist who wants to do that,” Melton says.

“Scientists make a grave mistake if they think people should just know (intuitively) about this,” he continues. “We are an important part of society, and it’s our obligation to talk to people about not only what we do but why we do it.”

Scientists should avoid making extravagant claims, like promising a cure for cancer in a decade. But there is nothing wrong with spurring the public’s imagination.

“There are two great problems that society faces now, at least as I see the world,” says Melton. “One of them is renewable energy. If I were a young person, I would be fascinated to figure how why chloroplasts in green plants harness energy from the sun so much more efficiently than our best solar panels.

“The second one, it won’t surprise you to hear, is renewable bodies. I think the concept of keeping my body healthy, healthy aging, is very interesting and fascinating… The public has a great appetite to increase their body’s natural ability to replenish and repair itself.”

More consistent research funding. Partnering with industry. Diversified support. Investing in education. Selling science’s story to the public. Good ideas all.

But there is one more quality that is essential for keeping biomedical research high on the nation’s agenda -- leadership.

Hamm argues for “a 100-year national strategy for investment in scientific research leading to breakthroughs in our understanding of disease,” while Magnuson calls for a presidential cabinet-level position to help guide the nation’s science and technology enterprise.

For Melton, it’s a matter of “setting the tone.”

National politics and policy debates have “devalued” science in recent years, says Melton, despite the fact that “science as a way of knowing has proved to be the most powerful way of understanding the great questions of life and, fortunately also a great economic engine.”

“It’s not that I mean we should have experiments going on in the White House,” he says. “I’m talking about setting the tone… That’s why we have a central government—to ask what’s important for our society, how do we solve problems and set a tone that engages society to help others.

“That’s what I mean by leadership.”

“What made America great?” asks Vanderbilt’s Caprioli. “In the early 1900s, we launched into the world. Why? What was in our spirit, our culture that allowed that meteoric rise? Is there something in our history that can give us a glimpse of what our solution should be?

“This goes very deep into the fabric of who we’ve become,” he says. “Who we’ve become is not all good. We have to understand the parts that are limiting us and get past them.”

Lisa A. DuBois contributed to this story

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