Gendelman has spent more than 15 years, the last eight of them at the University of Nebraska Medical Center in Omaha, puzzling over a central question. It's this: Why do certain cells, known as glia, act good in most people, nourishing the brain, but in some people turn evil, destroying the brain?
A second question: Can Mr. Hyde be turned back into Dr. Jekyll? Can Hyde's evil work be reversed?
Until now scientific questions and answers about these diseases have been buried under a mountain of political questions about one of five major tools Gendelman uses in his research: brain cells from aborted fetuses. The revelation last November that Gendelman used cells donated by a Bellevue abortion doctor created a controversy that dominated public attention this year, and almost certainly will do so again in the coming year. He no longer receives cells from the Bellevue doctor, but the cells he uses still come mostly from elective abortions.
Seeing only political responses to this most interesting of topics may have generated new questions from people on both sides of the fetal-cell debate. Those who abhor the cells' use because of their connection with abortion, and those who believe using the cells is proper because lives may be saved, may well wonder:
- How are the cells used? Do they play a minor or major role in the research? Aren't there alternatives that are less morally objectionable to some?
- How did research that started looking at one of the great scourges of our times, AIDS, branch out into Parkinson's disease and Alzheimer's disease? Could the three be related? How does that affect the prospects for cures?
- How did a researcher who'd held prestigious positions at three world-renowned institutions on the East Coast end up in Nebraska? How did he turn a basement office and one technician into a laboratory that boasts the latest technology, employs 40 researchers and assistants and explores eight categories of scientific pursuit? What learning opportunities does this offer UNMC students?
In an interview with StatePaper on Wednesday, Gendelman considered these questions. You'll find the answers about fetal cells in this story; look to Friday's StatePaper to discover how AIDS research branched out, and how Gendelman found his way to Nebraska.
Recreating the Brain
You want to study diseases that damage the brain; diseases like AIDS-related dementia, Parkinson's and Alzheimer's that rob their victims of the ability to think and function. You've got an idea that maybe the glial cells that nourish the brain's key component, the neurons, can turn against the brain and become its enemy. You've even got ideas about how to reverse this process - how to change the evil Mr. Hyde to the good Dr. Jekyll. But how to test your idea? How do you recreate the human brain in a test tube?
Simulating the brain in a test tube requires having three types of brain cells: neurons, glia and astrocytes. Gendelman and his colleagues in Gendelman's Center for Neurovirology and Neurodegenerative Disorders have five methods for getting these cells. One of the methods involves fetal tissue.
- Donated blood: This first method examines how white blood cells, the disease-fighting component of blood, get into the brain - and what they do when they get there. Gendelman's center receives donations of blood for these studies.
- Surgical resections: From hospitals in other states, the center receives the tissue left over following surgical removal of brain tumors. Some of this tissue is usable for science, as is some of the tissue removed from the brains of people with epilepsy.
- Rapid autopsies: This is the center's newest method, being pursued in an attempt to eliminate the need for using aborted human fetal cells. "That is going pretty well," Gendelman said of the effort. It involves getting permission to extract brain tissue very quickly after a person's death, so the three cell types needed will not deteriorate. So far, the center has succeeded in getting the astrocytes and microglia - but not the all-important neurons.
- Rat and mouse fetal cells: Most of the center's tests are run first on rats and mice, Gendelman said. "We only use the human cells as proof of concept. All the diseases we study - Alzheimer's disease, Parkinson's disease, AIDS dementia -- are human diseases. They're not mouse diseases."
- Human fetal cells: This is the only source of healthy neurons which will help answer the questions Gendelman and his center's researchers are asking. Neurons transmit the electrical impulses with which the brain tells the body what to do. They're the thinking cells. They're supremely important.
As you've read before, but perhaps not all in one place, the sample of brain tissue Gendelman receives from aborted fetuses is the size of a pea. The samples used to come within hours of the abortion from the Bellevue abortion doctor, but now come via overnight delivery from a facility in Seattle, Washington. The samples do not come from the abortion procedure its opponents call partial-birth abortion. Only cells from first-trimester abortions are usable, Gendelman said, because they grow and develop too much after that stage. There's a misconception that the cells come from late-term abortion, or even living infants, Gendelman said, and that's not true.
Now the statement that fetal cells are the only source of neurons that will answer these specific questions raises more questions: Why? What makes Gendelman's research so special? Read on, and you'll find out.
Food for Thought
Gendelman's science revolves around those glial cells mentioned earlier. They produce chemicals and substances that provide the food and nourishment the neurons to function effectively.
For many years, Gendelman said, scientists thought glial cells had no major role in disease. But years of work at several different institutions helped Gendelman and his various colleagues prove otherwise. Somehow, an "insult" to these glial cells - from a virus like the human immunodeficiency virus that causes AIDS, or from an abnormal protein associated with Alzheimer's disease - could turn the glial cells from nurturing to destructive.
So Gendelman and his partners would take different components of the brain, infect them with HIV or afflict them with Parkinson's, and try to get these purposely disease brain parts to mimic a whole brain. "Obviously to do that, you need all the players," Gendelman said. "You can't have the play without the principal stars."
Taking top billing in this play is the neuron. Once again, Gendelman gets neurons from aborted human fetal tissues, and only from that source. Critics of this approach have said neurons can be obtained from stem cells, thus eliminating the need for using morally objectionable fetal cells. Stem cells are the body's precursor or ancestor cells; they develop into all the body's different parts. Scientists have found ways to transform them into many different forms. It's a promising, exciting and highly publicized area of research.
The Whole, Not the Parts
But, Gendelman said, stem cells won't answer the questions he's asking. Here's the problem: Stem cells could be transformed into neurons, sure. But if you did, you'd get just that - a neuron. You wouldn't get a test-tube simulation of a working brain, which is what's necessary to prove that ideas for disease treatments would actually work in the real world.
You can produce the individual parts (with stem cells), but you can't produce the whole," Gendelman said. "It would be like Star Wars without the spaceships."
Recovering neurons from human fetal brains brings not just the neurons, but the supporting glial cells. The neurons can't live by themselves because they depend on the nourishment of the glial cells. The result is a more accurate test-tube representation of the human brain, a place where treatments can be tried with more assurance that they'll work in living people.
One of these proposed treatments is a novel approach: A vaccine for Parkinson's disease. It's being studied right now in Gendelman's research center. Other big successes at the laboratory involve doing just what was mentioned before: Treating brain-destroying diseases by turning "evil" glial cells back into good ones. It's already saved one Omaha woman's life, and helped inspire researchers in Israel to cure heal normally irreversible spinal-cord injuries in rats. Look for more on all those discoveries in the second part of this story, in Friday's StatePaper.
Gendelman thinks his ideas have promise. He thinks treatments or cures for diseases that rob people of their thoughts could come from his ideas. He uses human fetal cells as one of his tools because he believes finding cures for disease requires many different approaches. Other scientists take their paths, and he takes his.
"We're approaching things differently," Gendelman said. "We're all moving toward the same goal.
"That's a fundamental tenet of science, I mean, the search for the truth. You don't know if one approach, both approaches, no approaches, is going to work."
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This story originally appeared in Nebraska StatePaper on December 21, 2000.
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