The Science of Research

January 25, 2007

In a third-floor conference room in Building D on the campus of the Georgetown University Medical Center, Dr. Pedro Jose’s award-winning—and argumentative—research team is gathered around a long table for their weekly lab meeting.

“This is tough,” Jose, a diminutive Filipino-American, explains as I enter the room. “We look at raw data.”

A researcher is in the middle of presenting her progress from the past week, but Jose has no qualms about abruptly inserting himself into her talk.

“Why did you choose H8?” he demands, explaining that most scientists use H9 cells for similar experiments. The researcher stutters nervously and apologetically replies that she doesn’t know.

“No, don’t say that,” says Jose, cutting her off again, but this time he wants her to stand up for her decision. “You could have said, I didn’t agree with you.”

As soon as she finishes speaking, Jose is already onto the next activity. “Who’s next?” he barks, glancing up and down the table at the other researchers, who quickly avert their eyes and busy themselves with their notes. “Brad, do you have something good for us?”

“It’s the start of something, I think,” Brad replies, as he moves to the front of the room and pulls up a PowerPoint slide of a mouse’s carotid artery.

“Okay guys, this is your chance,” says Jose. “For your darts.”

For the next 45 minutes, the gregarious Jose, who is Chief of the Medical Center’s Department of Pediatrics and a faculty member in the Department of Physiology and Biophysics, continues to bring his own darts. Waving his arms wildly, he confidently probes deeply into his team’s experiments, questioning and challenging each slide on the screen and listening intently to every offhand comment his researchers make. All of these weekly discussions pay off: Jose’s lab was recently lauded for its discovery of GRK4 gene variants that can lead to high blood pressure when a high degree of salt is ingested.

Down a few stairs and around a few corners sits a man who will soon become the target of more than a few darts himself. Howard Federoff spends one day a week in Washington, preparing to officially become Georgetown’s Executive Vice President for Medical Administration—the highest-ranking Medical Center position—on Apr. 1. Federoff comes to Georgetown at a crucial time in the Medical Center’s history. The Center is slowly emerging from a deep abyss of debt, which has long been a drain on the University’s overall budget. At the same time, though, its scientists are bringing in major grants and producing research discoveries that could vault the school into the top tier of American medicine.

Dr. Ian Gallicano, a researcher in the Department of Cell Biology, is quick to justify the cost of the Medical Center’s research, referring to the debt as a Main Campus “myth.”

“I was talking to an English professor who was like ‘why do we even have a Medical Center, they’re always in debt,’” he said. “Without us, this place is a third-level college. You would lose more money than you can ever imagine.”

The Medical Center has been without a permanent leader since 2004, when Stuart Bondurant came out of retirement to serve as the interim Executive Vice President after Daniel Sedmak’s departure to Ohio State University. When Bondurant took the position, the University had a $30 million dollar operating deficit for 2004 and a predicted deficit of $35 million for 2005.

“My goal was to position the place so that it could successfully sustain its strong character and be positioned to successfully recruit a strong generation of leadership,” Bondurant said. “The goal was to bring the budget into a state of balance or close enough to a state of balance” to draw high-quality candidates for the top job.

He appears to have succeeded on both counts. On the financial side, the Center’s operating deficit was cut to $16.9 million. Bondurant implemented numerous expenditure control policies and divided the Center into four distinct sectors—the School of Medicine, the School of Nursing and Health Studies, the Lombardi Cancer Center and the Biomedical Graduate Research Organization—in order to eliminate duplication and ensure accountability.

As for his other goal, Bondurant managed to drag Federoff away from 11 years at the University of Rochester.

Sedmak, the former Executive Vice President, considers Federoff a capable replacement, calling him an “outstanding nationally and internationally recognized scientist.”

When the Medical Center’s budget was at its nadir, the University sold Georgetown University Hospital to a private health-care company, MedStar Health. MedStar now owns and operates the hospital, although the Medical Center works closely with the company on a plethora of projects. Federoff spoke positively about the University’s decision to sell the hospital, saying that it opened up opportunities for new collaborative research.

“The University weathered, and not uniquely, one of the most difficult times in academic medical center governance,” he said, explaining that the sale of the hospital took place during this period. “Looking at the future, one of the things that many institutions are focused on is translational research, where you take things out of the laboratory and into the clinical environment [and] we have an opportunity to expand our translational opportunities through our relationship with MedStar.”

Research is both a blessing and a curse for the Medical Center. On the plus side, research accomplishments draw public recognition, royalty dollars and top talent into the Center’s departments. On the other hand, research costs money, and lots of it—which is in short supply both here on campus and in the national biomedical research arena.

To start with, the equipment itself is often prohibitively expensive. Gallicano, whose research is funded by the National Institutes of Health, received a grant a year- and-a-half ago to purchase a confocal microscope for his lab. This piece of equipment costs between $400,000 and $600,000—roughly comparable to the price of a New York City studio apartment. Gallicano studies stem cells from adult humans and embryonic mice, focusing on prostate cancer and breast cancer; and the microscope is a crucial tool in his projects.

Dr. Radhakrishnan Padmanabhan, a professor in the Department of Microbiology and Immunology, faces a similar difficulty. His research, which is also NIH-funded, looks for antiretroviral therapies for mosquito-borne illnesses like dengue fever and West Nile Virus. Padmanabhan has identified core compounds that will inhibit three target proteins involved in the replication of the viruses’ genome. But he says that there are still between three and five years worth of work to do before a vaccine is found, and he needs the right tools to do it.

“We have identified some potential compounds, but we have to optimize these inhibitors,” he said. “That involves collaboration with structural biologists.”

Finding a structural biologist sounds easy enough, but Padmanabhan’s compounds require the use of an X-ray crystallography machine, which costs around $1 million. Because Georgetown does not have the funds for one of these machines, Padmanabhan must collaborate with the NIH and Purdue University.

Even as the price of science has risen, the budget for the NIH, the federal agency that provides most of Georgetown’s funding, has dropped in recent years. According to Don Ralbovsky, an NIH spokesperson, the Institutes’ budget has remained level at $28.6 billion for the last two years. Although this may sound fine, the budget has risen less than the rate of inflation, which makes a level budget as bad as a shrinking one.

“Federal funding has flattened out,” Federoff said. “We need to be more competitive to stay funded at the same level that we have been in the past.”

In 2005, the most recent year for which award data are available, Georgetown ranked 70th among institutions that receive NIH funding in terms of total research, winning 211 grants for a total of $71,798,074. As a comparison, the top-ranked school, Johns Hopkins, received 1,299 grants for a total of $607,222,589 dollars. Georgetown ranked 60th among NIH-funded medical schools, up from 63rd in 2004. The Congressional Appropriations Committee, which determines the NIH budget, will release the budget for fiscal year 2008 on Feb. 5, less than two months before Federoff will officially take over.

Gallicano agreed with Federoff’s dire assessment of the grant situation. Just today, he submitted a new grant proposal to the NIH, and he was not shy about hiding his apprehension.

“Grants that would have been funded three years ago are not being funded now,” he said. “How do you pick the top ten out of 100 when the top 25 grants are all outstanding?”

Gallicano said that larger labs with high-tech research facilities usually get about five percent of all available grants, while new labs get about two or three percent, leaving only two percent leftover for established small-scale investigators looking to keep their work alive.

“We’re not new investigators, and we don’t have big labs, so what do you do?”

For Gallicano, the much-maligned relationship with MedStar provides an opportunity for the translational research that Federoff talked about—a chance to transition between the clinical setting and the lab environment without ever leaving campus. The grant he submitted today was written with Lopa Mishra of Georgetown’s Department of Surgery. By working with MedStar transplant chief Lynt Johnson, Gallicano and Mishra are able to use clinical samples in their research.

“MedStar will give us pieces of tumors from human patients, and we’ll put them into mice, so we can see if the drugs diminish the size of those tumors,” he said.

When scientists do manage to win grants, they are personally allowed to keep less than half of the total award. The University takes a 55.2% overhead from each grant received from the NIH, which disappears into the Medical Center’s bureaucratic vortex to fund new research initiatives.

“I bring in about $1.2 million a year in direct costs for my lab, and over half of that goes back to the University,” Jose said. “What we are doing here is trying to make sure that Georgetown is competitive, and the overhead is necessary to make sure that Georgetown can continue to support meaningful research.”

Gallicano has found a way to avoid the enormous overhead for NIH funding by getting grants from outside sources, such as the American Heart Association and other medical foundations. Foundation grants have a much lower overhead, around 10%.

“It’s great for me, but it’s not that great for the school,” he said. “But there’s no other way to keep labs going right now.”

Not all hope is lost for financial redemption, though. Federoff mentions patents on new discoveries by Georgetown research scientists as a potential source of long-lasting income through royalties, citing Department of Pathology Chair Richard Schlegel’s discovery of the human papillomavirus vaccine, which can prevent cervical cancer, as an example. Patents have long served as a route to financial solvency for university-affiliated medical centers; the University of Wisconsin-Madison is still making money off of the 1924 discovery of the irradiation technique for vitamin-D fortified milk. Patents are reliable moneymakers once they’re in-hand, but securing one doesn’t come cheaply, either.

“In NIH-funded research, if an investigator makes a discovery … the right to file for patents rests with the institution where the investigator works,” Padmanabhan said. “It has to be really novel in order to justify the cost of applying for patents.”

Gallicano explained the monetary situation by saying that other medical schools operate with just as much deficit, but that Georgetown has a lower endowment to provide a cushion. Georgetown’s endowment is currently at $880.3 million; by contrast, Harvard has an endowment of $25.9 billion and the University of California’s endowment totals $7.3 billion. Endowment is not the only key to success, though: research powerhouse Johns Hopkins has an endowment of only $1.695 billion.

“Georgetown is one of the elite medical centers where the faculty both teach and do research,” Sedmak said. “When you have a medical school like that, you have to make sure you have enough resources to support that dual mission, and that’s a more expensive proposition.”

But just how elite is the Georgetown University Medical Center? In the 2007 US News and World Report medical school rankings, Georgetown moved up the list to 46th, ahead of area universities like George Washington and Howard, which failed to crack the top 50, but far behind perennial top contenders Johns Hopkins (2) and Harvard (1), as well as established state universities like the University of California-San Francisco (4).

Federoff said that raising the ranking will not be a primary objective for him, but also acknowledged that the school’s ranking does play an important role in attracting high-quality students and faculty.

“I don’t think it’s wise to focus solely on US News and World Report as an index of our quality,” he said. “That’s not to say that what US News and World Report says isn’t taken into account.”

With its growing research initiatives and shrinking debt, and with Federoff as its new leader, Georgetown seems poised for success. Of course, every administrator and every professor has his or her own ideas about what should and should not be taken into account, and what direction the Medical Center should take for its future.

Back in Building D, after his whole team had finished their PowerPoint presentations and hastily departed for their labs and offices, Dr. Jose stood next to his now-empty conference table, enthusiastically elaborating his personal proposal.

“I’ve gotten awards and I’ve beaten people from Berkeley,” he said. “Berkeley has more Nobel Prize winners than any other school. We need to work on that. We need to have more people in the National Academy of Sciences. That’s what I would do if I were running the place.”

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