Critical Mass

Donald Miller forged a national reputation for excellence during his 16-year tenure at the University of Alabama-Birmingham, helping build one of the country's preeminent hematology/oncology programs and overseeing leading-edge research into the molecular genesis of cancer.

But Miller, a Duke-educated physician who also holds a Ph.D. in biochemistry, isn't one to rest on his accomplishments. When a search committee from the University of Louisville contacted him two years ago about heading the James Graham Brown Cancer Center, he found the offer irresistible.

"I had a wonderful job at UAB, but I was very impressed with the excitement and opportunity for growth at UofL, as well as the camaraderie of the Louisville Medical Center community," Miller recalls.

"I was at UAB at a time when it grew from being a relatively small southern medical school to a major research institution. I had the sense that the same kind of transition was happening here. That's a very exciting environment in which to work: You can bring in new people, everybody starts getting their grants funded, and the cancer center begins to make progress almost weekly.

"That's what's been happening at UofL over the last two years."

In fact, since Miller became director of the Brown Cancer Center in 1999, he's brought in 24 new faculty members and $9.5 million in research funding. The true significance of the latter figure is understood only when compared to the amount of research money the cancer center received in Miller's first year -- $800,000.

"We're really starting from the ground up," notes Miller, a soft-spoken melanoma specialist who also serves as an associate vice president for health affairs at UofL.

"But that means we can build a cancer center based on the kinds of scientists and clinicians we want. We've begun to formulate a strategic plan that is almost independent of anything that was here before, with the goal of reshaping what this cancer center will be five years from now."

That plan, Miller says, calls for an annual research budget of $20 million by 2003 and the recruitment of 40 additional faculty members by 2006. By that time, university officials hope the Brown Cancer Center will have been designated a comprehensive cancer center by the National Cancer Institute.

There are 41 comprehensive cancer centers around the United States -- Miller served as deputy director of just such a facility at UAB -- but none are closer than Indianapolis or Nashville.

The role of these centers is three-fold: deliver first-rate patient care; sponsor community outreach and cancer prevention programs; and -- perhaps most important -- conduct basic and clinical research.

The third leg of this triad represents something of a departure for the Brown Cancer Center, which for much of it 20-year history has focused mostly on patient care and cancer prevention.

The new attitude is the result of shifting institutional priorities, Miller notes. UofL President John Shumaker has made it the university's mission to establish itself as one of the country's top urban research academies in the next decade. A key component of that plan is to attain comprehensive cancer center status for the Brown Cancer Center.

To that end, UofL has dedicated a tremendous amount of resources to building the cancer center's infrastructure. Miller declines to discuss specifics, but he says the figure is "more than has been dedicated to any other university institution in the last decade."

Among those resources are monies from the state's Research Challenge Trust Fund, more commonly called "Buck for Brains" (see related column), which matches private contributions with state money to fund endowed chairs and research efforts.

Miller himself was recruited with the help of grants from the Research Challenge Trust Fund and Louisville's Brown Foundation, and he now holds the title of James Graham Brown distinguished professor of internal medicine and hematology/oncology.

Several university-supported laboratories have been vital to the development of the cancer center's research programs, too, including state-of-the-art DNA-sequencing facilities, a laser-capture microdissection lab, and a flow cytometry center for cell marking and sorting.

The Brown Cancer Center also houses a sophisticated molecular modeling facility that helps researchers design the three-dimensional structures of investigational drugs.

"All of these things are crucial to help people do cancer research," Miller says. "They put us on the leading edge."

And more is on the way. In June, UofL broke ground on a $12 million Molecular Imaging Research Center that will house two nuclear magnetic resonance spectrometers, which allow 3-D views of molecular structures. Using information from the Human Genome Project in conjunction with NMRs, researchers hope to identify cancer molecules and develop new ways to inhibit their growth.

The center also will feature Kentucky's only positron emission tomography/computed tomography, or PET/CT, imaging system. A PET/CT scanner produces highly detailed images of living tissues and can greatly improve the accuracy of cancer diagnoses, making it an extremely valuable clinical tool.

When the Molecular Imaging Research Center is complete in early 2002, UofL will have more NMR capability than any other cancer center in the country, Miller says. Furthermore, the two cyclotrons needed to support the PET/CT scanner will allow researchers to create exotic isotopes in-house, enhancing ongoing studies.

"This puts the cancer center at the forefront of cancer research and treatment," Miller says, "and moves us closer to designation as a comprehensive cancer center. The ability of our researchers to investigate cancer and develop new therapies will be second to none."

Plans are progressing so well at the Brown Cancer Center that Miller has had to revise his goals upward. In fact, the largest current stumbling block to achieving the NCI designation is something relatively simple -- a lack of adequate lab space for new researchers to occupy.

"Without good lab space, you can't recruit good scientists because their labs are more important than their homes," Miller observes, only half-joking. "Up until now, we've been able to get good people by having that lab space available."

New research facilities will, however, be opening soon -- the Delia B. Baxter Biomedical Research Building is slated for dedication in the fall of 2002 -- and the university has committed to expanding the Brown Cancer Center's research space from 21,000 square feet to 194,000 square feet by 2004.

Miller estimates that by sometime next year, the center will have assembled the right mix of equipment, facilities, lab space and researchers to achieve "critical mass and really start moving things forward."

This means an aggressive research program focused on the prevention of cancer at the molecular level by designing drugs that target misbehaving cells or "turn off" cancer-causing genes. Miller, who was director of UAB's Bolden Molecular Genetics Lab, has quite a lengthy record of achievement in molecular medicine, beginning in 1975 when he studied gene regulation as a researcher at the U.S. Public Health Service.

"We were just learning how genes were turned on and off," Miller recalls, "so we've come a long way since then."

Today, Miller and his UofL colleagues, including researchers John Eaton, Ph.D., and Paula Bates, Ph.D., are readying an entirely new cancer-treatment compound for clinical trials. Called a G-rich oligonucleotide, the compound is a short piece of DNA that binds to the spot in chromosomes where they divide, blocking the synthesis of DNA and stopping the development of cancer cells.

"It's an incredibly exciting time," Miller says. "I think the work that's going on here now, and the work that will be done by the people we're bringing in, will really put us on the map in terms of being able to develop more-effective and less-toxic drugs for cancer.

"We hope we'll have three or four new drugs going into clinical trials from this cancer center every year when we get geared up."

The new focus on research does not, however, mean the Brown Cancer Center plans to reduce its traditional role as a provider of first-rate patient care.

In addition to the new PET/CT scanner, the Brown Cancer Center is working to enhance patient care with multi-disciplinary clinics.

"This gives patients one-stop shopping," Miller explains. "They can see a surgeon and a medical oncologist in the same visit, which has been wonderful in terms of allowing us to attract patients from a farther distance and to do collaborative clinical trials."

The center's continued dedication to patient care mirrors its director, who among research scientists is somewhat unique for his ongoing desire to treat patients in a clinical setting.

"I think the two roles are very complementary," Miller says. "Being a scientist makes me a better melanoma doctor, and being a better melanoma doctor makes me a better scientist."

Al LoBuglio, M.D., director of UAB's comprehensive cancer center, calls Miller's combination of research acumen and clinical care "an amazing knack."

"He's one of those unusual people who can have a successful research career, hold an administrative role, and at the same time have an amazing commitment to and appreciation of his patients," says LoBuglio, who has known Miller for 21 years.

As proof, LoBuglio notes that Miller still has patients who drive from Birmingham to Louisville to receive treatments.

"That's because his patients have such a high level of regard for him personally," Lobuglio says.

Miller's desire to interact with patients stems, in part, from the boyhood experience of seeing a loved one receive treatment for head-and-neck cancer.

"I was very close to my grandmother, who had cancer when I was a child, and I spent some time in the waiting room of University of Iowa Hospital," Miller recalls. "I was just very excited about what I saw there; I knew from the time I was 8 that I was going to go to medical school."

That early decision has been fortuitous for UofL. By all accounts, Donald Miller is exactly the right person to guide the Brown Cancer Center into a position as one of the country's most respected research and treatment facilities.

"We had some fine candidates for the job of director, but we're very fortunate Don left Alabama to come with us," says Joseph Chalfant, co-chair of the Regional Cancer Center Board of Directors and a member of the search committee that brought Miller here.

"Don has the research vita to attract sharp, young researchers who can grow with our program, and he also has an outstanding bedside manner. Sometimes a good researcher can't even talk to people. And sometimes a good practitioner doesn't have vision. Don has both."

And what does that vision hold for the future of the James Graham Brown Cancer Center?

"I think the future is very bright," says Miller, who recently received the Founder's Medal for lifetime achievement from the Southern Society for Clinical Investigation.

"I think the future will see the Brown Cancer Center become the leading cancer center in the upper Ohio Valley. We would like for it to be recognized as a major player in cancer research -- in the Top 10.

"Right now, we're well on our way."