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Translating Basic Science
How Bench to Bedside Progress is Bringing

How Bench to Bedside Progress is Bringing
Maryland into the Spotlight

Discoveries are the life blood of basic science, which aspires to solve the mysteries of disease at the deepest molecular level, and then translate those answers into vaccines, drugs, and other kinds of treatments to be utilized in clinical medicine. The University of Maryland School of Medicine is building an international reputation in this field, thanks in no small part to its three newest basic science chairs, Drs. Meredith Bond, James Kaper, and Richard Eckert.

Photographs by Rick Lippenholz

Meredith Bond, PhD, whose primary research delves into the science behind heart failure, has been heading the department of physiology for four years. James Kaper, PhD, who specializes in the molecular pathogenesis of infectious diseases, became the chair of the department of microbiology & immunology in February, after more than 20 years as a professor and prolific researcher at the school. Richard Eckert, PhD, whose work focuses on understanding how skin cells function to protect people from illnesses and how those cells are altered during disease states such as skin cancer, was appointed chair of the department of biochemistry & molecular biology in November 2006.

As they gather for a roundtable discussion of the importance of science in medicine, the three share an easy camaraderie, a connection they’ve cultivated since Eckert’s arrival. “The basic science chairs have started going out every month or so for dinner,” explains Kaper. The group, which also includes Michael Shipley, PhD, the chair of the department of anatomy and neurobiology, and Edson Albuquerque, MD/PhD, chair of the department of pharmacology, “discuss common problems and experiences,” according to Kaper.

One of the biggest issues they all face is funding their research. Although grants to the medical school have increased every year, getting those research dollars has become more and more competitive. The NIH research budget is diminishing, as is the state and federal government’s willingness to finance experimental science. This situation could have a devastating effect on the field in the very near future. “The NIH budget is being cut outright in terms of research dollars, and then we’re losing purchasing power because of inflation, and along with reducing the things that we’ve done, it’s also really turning off the next generation of students,” laments Kaper. “We may be losing a great number of very talented researchers in the future who see how their mentors struggle and sweat and worry about grants, and that’s not appealing. On one hand there’s the excitement of doing the science, but then they also see the frustration and angst about grant support, and that’s sure to be a problem in the future. It’s already a problem now.”

Bond agrees. “The spigot has been turned off, and the money available to support original ideas and allow them to grow to fruition is being stifled,” she says. “So science can’t move on as quickly as it would like, because the funds aren’t available. I don’t think anybody is advocating funding research that is mediocre. But we’re at the point where we need to find ways to fund research that is truly outstanding. Because a number of very bright people with spectacular ideas are not able to take the next step and develop those ideas into significant discoveries.”

There are discoveries with great potential to be found in every basic science department, but Kaper is especially excited about potential success in the field of vaccine development. “There may be a possibility of vaccines to treat non-infectious diseases [such as cancer],” he explains. “Dr. Scott Strome, who was recently profiled in the Bulletin, is also working on a therapeutic—rather than preventive—application for vaccines. As we know more and more about the basic science of underlying diseases, hopefully we’ll learn enough to take early steps towards preventing disease, as opposed to having to take later steps for therapeutic treatments.”

Bond concedes that disease prevention would be ideal, but “that requires resources and a little bit of a different philosophy,” she says. “In the past we’ve had clinical trials with patients who are symptomatic. But we’ve got to step back before that to people who are at risk but are not symptomatic. Those individuals have to be followed a lot longer in a clinical trial, of course, but they’re much less likely to be critically ill for a much longer period of time. So our goal is truly personalized preventive medicine. I think a lot of people are moving in that direction, but there will be a few little hiccups along the way. And there will, of course, be some financial needs in order to move that along a little bit.”

Dr. Richard EckertWith the aforementioned cuts in NIH research funds and other government contributions, those financial needs will have to be met in other ways. “Philanthropy becomes all the more important to fill in those gaps,” Kaper declares. “Compared to some other state universities, we get about half the money per capita per medical student than most of our peer institutions. This institution does not have a long history of philanthropy, but one of the great things Dr. Wilson did when he became dean was really focus on fund raising. He really did a terrific job, but much more is needed, and Dr. Reece is certainly carrying on with that tradition. But it’s so important—for the advancement of the whole institution, not just the basic sciences.”

Helping its case is the fact Maryland is attracting top students and professors because of its excellence in translating basic science into clinical applications. The school boasts a long tradition of “bench to bedside” excellence because its physicians and scientists are within the medical school, which has a strong partnership with the Univer-sity of Maryland Medical Center. “I think there is a big advantage being at a medical school,” proclaims Bond. “There are a number of people who are doing very important basic science on a number of undergraduate campuses separate from a medical school. But they have somewhat of a geographical hurdle when taking that to the next step. They don’t run into the clinicians in the corridors, and they don’t get a chance to see as easily as we do what problems need to be investigated and how we can best interact with clinicians. At research institutes that don’t have direct interaction with hospitals, you often meet people who have a yearning to be on a campus like this. So it’s an attraction for people to come here, the fact that there is such a rich clinical environment.”

While Eckert may joke that bench to bedside progress takes “thousands of decades,” he agrees that it is critical to the school. “I think the most outstanding institutions right now are investing in parallels in basic and clinical science, because there’s clearly a realization that the strongest medicine, the strongest advances, come out of both schools,” he says. “We’re well on the way to doing that kind of thing. I’m the newest here, but if you look at the way the school’s progressed, there’s really been an investment in bringing in investigators who can do good fundamental science, especially in the basic area, but also in the clinical areas. That’s fueling our rising profile.”

Dr. Meredith BondHowever, it’s usually the clinical science that gets the most attention—and money. “From the point of view of philanthropy, basic science is just as critical to the advancement of medicine as what people are doing in the clinics with patients every day,” says Bond. “But it’s sometimes difficult for us to be able to communicate that effectively to people outside these walls. However, there is plenty of evidence that basic discoveries that initially appear not to have any obvious clinical advantage have enormous clinical impact down the line. So it’s up to us to be able to communicate the importance of that.”

Of course doing so isn’t easy because of the unpredictable nature of basic science discoveries. “There’s no easy, predictable path, and there are sometimes dead ends,” Bond concedes. There are also surprising discoveries.

“There is a worm that actually revealed how cells normally die,” Eckert explains. “And all those genes are found to be present in humans. So it’s opened up a whole area describing how cells are remodeled during development and are naturally taken out of the body by these processes and these genes, which is particularly of interest in cancer development. The whole of what is called apoptotic cancers were discovered in a worm. And it’s washed over the rest of biomedicine. People don’t really appreciate that unless we tell them. So [to get the word out] you take a few good examples and go out and tell people how what we do makes an impact.”

One area in which basic science has had an amazing impact is the field of recombinant DNA. “The whole genetic revolution, in terms of genetic engineering, is based on basic curiosity about little viruses that affect bacteria,” Kaper explains. “These are viruses that don’t affect humans, but they cause disease in bacteria. That’s not much of a tragedy for the bacteria, but looking at the phenomena, how some viruses can infect one bacterium but other viruses couldn’t affect the same bacterium, scientists discovered that these organisms and bacteria had enzymes that restrict what viruses can do. That was purely a laboratory phenomena initially, but from that came the discovery of restriction enzymes, which allow us to now do cutting and splicing of DNA. That was a very fundamental, very basic observation that had unbelievable consequences.”

Such important discoveries have forced basic science to re-evaluate the way it works. “If you go back 20 years, you could focus on a series of technologies in your own lab, and you could make discoveries, and it was fine,” says Eckert. “But then there was a technology explosion. Jim alluded to the techniques of modern molecular biology, which allowed us to do things that were just unfathomable. That changed things amazingly over only two years. So you went from that to a level where all these things were automated, to some extent, and then new technologies came on board to give you a better look at proteins. And then you could scan the whole genome at a time. And then the whole genome was known. So suddenly the contributions that you make are not only fundamentally in your lab, in your focus; they’re expanding in a broader way.”

Dr. James KaperKaper agrees. “The very traditional role of basic science used to stop at elucidating basic mechanisms but not going beyond, except for maybe going to the next basic mechanism,” he says. “But now there’s much more integration between basic scientists and clinicians, in terms of trying to apply and translate basic properties and understandings into an understanding of disease physiology and then into bringing the diseased patient back to health.”

This integration between the sciences is forcing a change in the way basic science is taught. “There are a lot of didactic courses over the first 18 months or two years of medical school, where students learn the course material,” Bond explains. “But the one thing that a good graduate student also must learn to do is to be collaborative from early on. It’s our job as mentors to encourage that. So our students can go to another lab, and sometimes even be the glue between two labs, and learn a new technique, look at a different way of doing things and be able to incorporate that into what they’re doing. The old days of the student just sitting at the bench doing a confined experiment are gone. The pace and the competition are just too rapid.”

Eckert agrees. “Students now are trained more broadly in many ways, out of necessity,” he says. “We’ve developed larger, programmatic, ’umbrella’ programs that are designed to challenge students more broadly and in different disciplines. Because the range of technologies we can now bring to bear—my lab or any other lab can’t match it alone. You have to find people to help you address issues. And when you do that, things progress much faster, and there’s more breakthroughs in terms of disease. I think [basic scientists] are going to be increasingly working as teams to conquer things.”

Bond is looking forward to this trend toward teamwork in science. “It’s going to allow us to attack thorny and difficult issues more easily, if we truly can work as a team,” she believes. “We’ll be bringing to bear on a problem a chemist and a bioengineer, plus a basic scientist and a clinical investi-gator, putting all of their expertise together. The challenge will be to effectively communicate amongst all those people with diverse backgrounds. Challenges are opportunities,” she says with a smile.

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