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The Making of Medical Pioneers
By Melissa A. Kruse '01

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Dan Michele - click photo to enlarge image
Dan Michele

Before he graduated in 1995, Dan Michele caught a bug. The infection spread throughout his body during his graduate career at the University of Michigan and, still today, at the University at Iowa, he sees no cure in sight. His symptoms? "Curiosity about how things work and a love of 'the hunt' for the answer," he says. His condition has no formal name, though "medical research" points most accurately towards it.

The current vehicle for Michele's "bug" may eventually yield treatments to quell the pains of muscular dystrophy patients.
Michele believes Calvin did a good job at preparing him for the rigors of graduate school, both academically and scientifically. He worked with biochemistry professor Larry Louters for three summers.

"The greatest impact this research experience had on me was learning to love science…from the contagious enthusiasm of Dr. Louters. During this research, I caught the 'bugs' that most biomedical scientists have," Michele said. "I view science as a method of understanding complex puzzles. As our knowledge grows, the complexity increases, but the tools to study science also advances such that we can now study things that before were impossible.

"This keeps me excited on a daily basis."

Calvin's prime purpose for research is teaching. While some larger institutions like the University of Michigan conduct research with the objective to go where no one has gone before, Calvin provides an environment for students to ready themselves for that type of research and to cultivate their views of such on an ethical level. So, upon leaving the state-of-the-art labs along the corridors of the new Doc DeVries Hall, these future medical professionals are prepared to unlock the final frontier.

Biology professor David DeHeer says at Calvin the process of the research is emphasized more than the actual outcome, because it gives students a glimpse into what their careers will be like—because students generally learn more by doing rather than listening in a lecture setting.

"Getting your hands involved in scientific research is a powerful application," he said. "You learn by doing. You can read about how to make a cake, but actually doing it makes all the difference."

DeHeer and Joy Bonnema, also a biology professor, have been studying the cells that loosen artificial joint implants, with their students. As implants like those in the hip move, they wear down, producing microscopic debris eaten by "macrophage" cells.

"Macrophages are my very favorite cells in the whole world," DeHeer said. "They're just so cool; they do a million things, and in this case, they cause inflammation."

"We're trying to understand what makes those little cells get all excited and how to quiet them down," said DeHeer, who began delving into the subject in 1991.

"It's kind of a garbage disposal part of the body," said Bonnema, who joined the effort four years ago. "It cruises around like Pac Man, looking for things that shouldn't be there or things that are in excess to eat up." When the macrophage burns out, it can trigger an inflammatory response in nearby cells.

Larry Louters - click photo to enlarge image
Biochemistry professor Larry Louters is researching the signaling involved in sugar uptake, related to diabetes.

A short walk from the macrophage lab in DeVries Hall, brings us to another project. Biochemistry professor Larry Louters is researching the signaling involved in sugar uptake, related to diabetes. He's interested in what signals a cell and what causes it to increase how much sugar or glucose it takes up.

This past summer he and some students worked with mice and a tissue culture line called fibroblast cells, which can be stimulated and developed into fat cells or muscle cells, depending on their environment. His project searched for what regulates sugar uptake into muscle cells and fat cells.

"I'd classify this research as basic. We're trying to see how things work, more than actually trying to find new molecules or new medicines," said Louters. "We're not on the cutting edge as far as drug discovery. What we do is take what other people discovered and try to figure out how that works. In the process, we learn more about how cells work and that, in turn, feeds into developing new drugs, new approaches. Because if you think about what goes wrong in diabetes, there are maybe 20 steps-and we only know three of them. If we can discover all of them, then we can design drugs that affect each of those steps and potentially find one that is good for diabetes."

David VanDyke, a senior, worked with Louters this summer. He said it was a good experience because Louters was less interested in receiving large amounts of data than in teaching-giving guidance rather than controlling the students' work. "This really allowed us to learn about the investigative nature of the research process," said Van Dyke. "We were really participants in the research, not just assistants."

But all of the research and studying means little if a student's ethics are in the wrong place. Part of being a biology student headed for the medical profession includes juggling some pretty heavy ethical questions. Sometimes these weary, searching souls need guidance to—or ownership of—their views in the ever changing world of science.

Hessel "Bud" Bouma - click photo to enlarge picture
Biology professor Hessel "Bud" Bouma works primarily in the field of medical ethics and keeps pace with embryonic research developments.

Enter Hessel Bouma III, biology professor and ethical guru on the topic of embryonic stem cell research. The controversy surrounding the topic as of late has been whether or not the research should be federally funded.

Working primarily in the area of medical ethics, Bouma keeps pace with embryonic research developments. He is in favor of federal funding for the research because with government funds, the work has to go through an ethics committee. When it stays in the private sector as it is now, there is no ethical review for it. "More heinous things take place in the private sector than if it were under public scrutiny," Bouma said.
Some of these "heinous things" include the over production of embryos at fertility clinics. The way Bouma sees it, there are four options: freezing the embryos and adopting them out, freezing them indefinitely, destroying them or using them for research.

"I don't see a big moral difference between destroying them and using them for research," he said. "But I would much prefer the first and second options."

Bouma will be teaching a section of "Developing the Christian Mind," in January, an interim course on medical ethics, in which embryonic stem cell research will be a topic. His biology 115 classes dealt with the issue for the first time this fall. Bouma says that students usually take a utilitarian stance on the issue at first, but as they think about it further, they reconsider their position or at least become more cautious about it.

"I see my task as an instructor in a college such as Calvin to help students identify their world view and inform them on a Christian world view and the variations of opinion that may be found in the Christian tradition," said Bouma. "But then they have to take ownership of their views. If I can help students to understand the moral underpinnings, to see how they got where they got, and where there might be moral inconsistencies, I feel I've served the student fairly well."

Dan Michele has also dealt with ethical issues in the realms of the unborn, in a project involving the genetic diagnosis of congenital muscular dystrophy patients. These patients struggle with a very severe form of muscular dystrophy, which has no cure and usually kills by age five. Patients and families are usually desperate for a diagnosis, which comes with two consequences: genetic counseling for the parents wishing to have more children or genetic screening of the developing embryos, which could result in the choice of pregnancy termination or embryo selection. The latter is highly debated on ethical grounds, says Michele.

"The genetics research helps our basic science research in understanding the genes that cause muscular dystrophy but, in turn, the research creates very important ethical issues for the patients and their families which would not otherwise be issues. I tend to favor the patient's/family's right to know the diagnosis, but the ethical ramifications are difficult to ignore."

Like Michele, DeHeer's research poses many similar ethical dilemmas. Discussions about such are usually brought up in the lab to challenge students to think about the ramifications of their work.

"We assess and manipulate the DNA of a cell and try to understand how DNA controls other cellular activities," said DeHeer. "These are things that a biotechnology practitioner does too. Imagine the kinds of questions that we can ask: When is it OK to manipulate DNA? Is it OK to do so in cells? Tissue? Organs? Animals? People? We can have lively discussions with our students about these and related topics."
Another such topic could be the whole topic of artificial implants.

"Imagine that your elderly grandparent, who is ill and not very active, broke his hip. The only way it can by repaired is by surgically implanting a new one, the procedure is costly, requires extensive therapy for a long time and may not necessarily improve markedly your grandparent's quality of life. Should the surgery be performed? Who should make that decision? If you were the physician, who would you consult? These ethical questions and more can be asked," said DeHeer. "And we do that with our students."

Having talked about these kinds of issues before has helped Kristin Hoving '00 who struggles with the ethics of her career on a daily basis. Hoving, a research project manager at the University of Chicago Hospital in Chicago, works in the leukemia program. She acts as a liaison between drug companies and doctors and patients. Part of her job includes putting patients on clinical trials with experimental drugs. Patients are warned about the drugs and sign a consent form. They can back out at any time for any reason.

"These people are terminally ill to begin with and so many have underlying health problems," Hoving said. "Most of them end up dying, but there are good results, too."

Most of Hoving's studies use phase three drugs, or drugs that have already been tested on animals. But there's a point at which the drugs must be tested on people, she says.

"I don't like to think of people as lab rats—I don't like to think of lab rats as lab rats. But at the same time, there's no way they'd make advances in leukemia research if they were not able to test on these people," Hoving said.

Fritz Rottman '59, has seen a lifetime worth of research. He was chair of the molecular biology department at Case Western University, where he taught for 18 years. He worked in the area of molecular genetics and gene discovery. Rottman is now retired, but still serves as a consultant for a biotechnology company and is a trustee for the new Van Andel Research Institute in Grand Rapids.

Rottman's whole research career has been involved with understanding the genetic code. The main objective of his work has been to define the components of diseases in molecular terms relating to specific genes, for the opportunity to have a new impact on the disease process by developing new drugs, using recumbent DNA.

"We should be doing this as Christians," Rottman said. "Some people will make the argument that we shouldn't be tinkering with our genetic make up. For myself, where I draw the line is between somatic cells or fully developed cells vs. germ cells.
"If you understand a specific disease, such as Parkinson's, and if at some point it's possible to insert a gene into a tissue and have that gene expressed which will help alleviate the symptoms of that disease in that individual, I believe that's morally defensible and is part of our mandate," Rottman said. "This is in contrast to trying to change the whole germ cell line of an organism-that is morally indefensible."

Rottman hopes that it will be possible through the information that is now being generated in the field of genetics, among others, to develop new vaccines, antibodies and other precautionary measures to ward off frightening prospects, such as bio-terrorism.

"To me, the whole pursuit of knowledge and science is quite indifferent," Rottman said. "How it is applied and used is where the ethics and morality come in. Seeing some of the discoveries that have taken place has been awe-inspiring. It speaks to my Christianity in a positive way."

The January Series 2002
Speakers include Jeremy Rifkin on "The Biotech Century" and James Peterson on "Should we Change our Genes?" Listen in Real Audio!

Calvin Lecturer
Physicist David Van Baak is representing Calvin at lectures around the world

The Human Genome Project

Christian Medical & Dental Associations
Offers a Christian perspective on topics in medicine and medical ethics

The Van Andel Research Institute in downtown Grand Rapids is a key part of Michigan's Life Sciences Corridor

Science Departments at Calvin:
Chemistry & Biochemistry
Geology, Geography & Environmental Studies
Physics & Astronomy

Biology Dept. Research
Student research projects, summer 2001

Research Facilities at Calvin
DeVries Hall of Science and th
e West Michigan Regional Lab

"Calvin Prof Seeks Dry Eye Cure"
Dr. John Ubels; July 12, 2000

Medical ethicist Hessel Bouma has advised a variety of organizations on topics such as stem cell research, human cloning, and physician-assisted suicide.

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