Sunday, February 25, 2001

Rapid Autopsies the Tool in Arizona, Nebraska Quest for Neurons

Editor's Note: This is Part Two of a two-part story on rapid autopsies. Part One reported that University of Nebraska Medical Center scientists are traveling next week to observe rapid-autopsy techniques at a research institute in Arizona.

LINCOLN - Rapid autopsies used to obtain brain tissue for medical research are exceedingly complicated and difficult, but offer fascinating scientific rewards for the effort.

Scientists at the University of Nebraska Medical Center are in the intermediate stages of developing a rapid-autopsy program, so they can stop using aborted fetal tissue in trying to treat Alzheimer's and other diseases. Anti-abortion activists and politicians have put pressure on UNMC to stop using the aborted tissue, and are trying again to ban its use after a legislative attempt failed last year.

Next week UNMC scientists will visit a research institute in Arizona that became a pioneer in rapid-autopsy techniques because of a ban on fetal-tissue research in that state. Arizona's ban has since been ruled unconstitutional, but Sun Health Research Institute's experience continues to be of interest to scientists around the country. The Sun City, Arizona institute's lineup of visitors includes researchers from UNMC Tuesday through Friday, Wayne State University in April, and New York University sometime in the spring.

Rapid autopsies are performed on people who have agreed to donate their brains to science. In the case of Sun Health's around 2,800 donors, they're people who have put stickers on their driver's licenses and medical charts that indicate they're brain donors. They've also informed friends and family so that as soon as they die, someone will call Sun Health's 24-hour autopsy-team hotline.

They're called rapid autopsies for a reason, after all. It turns out that when brain activity ceases and person is clinically dead, many brain cells die off and become useless for research. But, some cells can survive if doctors can extract them within an hour of death. So a team of doctors, nurses, technicians and others must be on call 24 hours a day, 365 days a year -- because people don't always die from 8 a.m. to 5 p.m. on business days.

"You have to have attended to every detail in advance as far as possible," said Joseph Rogers, president of Sun Health.

When brain donors die, they're brought to Sun Health. Doctors remove a 40-gram sample of brain tissue, about half the size of your fist. The procedure is not disfiguring; donors can still have an open-casket funeral.

The sample is immediately plunged into an ice-cold nutrient solutions. Chemicals are then used to disassociate, or dissolve, the tissue sample into its several different component cell types. These cells are then centrifuged -- spun around at extremely high speeds -- so that they clump together in different groups, based on their weight and other properties. Three types of cells are put in fancy test tubes with nutrient solutions that approximate conditions in the living brain, and the test tubes are placed in incubators that keep them at body temperature. The cells attach to the bottoms of the test tubes -- and survive.

"Now we've got for the first time living cells from Alzheimer's patients that we can test," Rogers said. "You can't test drugs on dead tissue. They don't do anything."

There are three cell types Sun Health works with: Neurons, microglia and astrocytes. These are the same kinds of cells UNMC now gets from samples of fetal brain tissue, but would like to obtain from rapid autopsies.

Unfortunately for the UNMC researchers, studying Sun Health's techniques won't mean an instantaneous ability to abandon fetal tissue. "With microglia and astrocytes, it took us six years just to work out the details," Rogers said. "The neurons are still a work in progress."

And there's the problem. UNMC's five reported rapid autopsies have yielded the support, or helper, cells called microglia and astrocytes, but not the all-important "thinking" cells, the neurons. (For more on the roles of these cells, see StatePaper's article, "Gendelman Explains Science Behind Fetal-Tissue Research.")

"We don't get very many nerve cells that are still alive," Rogers said. They're many times more fragile than astrocytes, which Sun Health has managed to keep alive for several months; and microglia, which last for two months.

The neurons can be kept around for one month, but they're not functional like the astrocytes and microglia. The process of separating the neurons from the other cell types amputates the nerve fibers, the all-important connections between neurons that form the basis for how the brain functions.

"We can't get the nerve fibers to re-grow," Rogers said. It's been a major achievement just to keep the neurons alive for short periods of time. "The nerve cells are extremely fragile. But in some ways, they're the prize. It is loss of nerve cells, and the connections between nerve cells, that cause Alzheimer's disease."

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This story originally appeared in Nebraska StatePaper on February 25, 2001.

Saturday, February 24, 2001

UNMC Scientists to Study Rapid Autopsies in Arizona

Editor's Note: This is the first part of a two-part story. Look for Part Two in Sunday's StatePaper.

LINCOLN - Dr. Howard Gendelman and a team of University of Nebraska Medical Center scientists are traveling to an Arizona institute next week to further their search for research alternatives to aborted fetal tissue.

Scientists at the Sun Health Research Institute in Sun City, Arizona, have extensive experience with rapid autopsies. That's the technique UNMC started pursuing last year so it can stop using tissue from elective abortions in its effort to treat Alzheimer's disease, Parkinson's disease and AIDS-related dementia. For more than a year now, UNMC's research has been at the center of controversy and attempts in the Legislature to ban it.

Sun Health researchers have had limited success in keeping alive neurons, the brain cells that are key to Alzheimer's research at UNMC and other institutions. They've had far more success working with two other types of brain cells, astrocytes and microglia, that UNMC researchers have also successfully obtained from rapid autopsies in Nebraska. UNMC so far hasn't reported success in finding living, scientifically useful neurons.

Rapid autopsies must be conducted quickly, within an hour or two of the donor's death. The science behind rapid autopsies is some fascinating stuff; you'll find some interesting details in the second part of this story, appearing in Sunday's StatePaper.

UNMC isn't the only institution interested in Sun Health's work. Scientists from Wayne State University will visit in April, and New York University researchers sometime this spring, said Joseph Rogers, president of Sun Health. His institute has perfected a brain-donor program which works so fast that it allows doctors to obtain small amounts of still-living tissue from a person who is clinically brain dead.

"I think the same methods should be applicable in any laboratory setting, and we are more than willing to share these techniques, especially with talented people like Dr. Gendelman and his scientists," Rogers said.

Gendelman said he and four other UNMC staff would learn about Sun Health's approach to the complicated logistics involved in brain-donor programs and rapid autopsies, and share their logistics ideas and scientific discoveries in return.

"I look at this as a mutual exchange of ideas between two of the premier groups in the country who are using these types of techniques," Gendelman said. While there are many institutions across the country using fetal tissue in medical research, Gendelman's Center for Neurovirology and Neurodegenerative Disorders is one of just a handful seeking alternatives to using fetal brain tissue.

Going on the four-day trip starting Tuesday will be Gendelman, two technologists, a graduate student and William H.C. Brown II, coordinator of UNMC's rapid-autopsy program. The trip is the latest development in UNMC's search for alternatives; earlier, the medical center hired Brown, and before that purchased a highly specialized and expensive microscope to aid the rapid-autopsies program.

Rogers and his team in Arizona have some unique advantages in finding brain donors, which Gendelman's team may not be able to match. Sun City is a retirement community of 140,000 people northwest of Phoenix where the average age is 72 and the minimum age is 55.

"You need a mature and personally generous community to make this work," Rogers said. "Senior citizens are much more mature about their earthly body; they're not so concerned about a beautiful funeral service as they are in getting to heaven.

"The people in our community have signed up for our program in droves." Specifically, two percent of residents -- or about 2,800 people -- have taken steps to ensure Sun Health's 24-hour rapid-autopsy team is notified immediately when they die. They need not be concerned about a beautiful funeral, however. Rogers said his team's technique for removing brain tissue is not disfiguring, and allows for an open casket at the funeral.

Rogers said that when he worked with a brain-donor program in Massachusetts, he had to draw on an eight-state area to find the number of elderly donors he now has in an eight-mile radius. A comparison of elderly populations between Sun City, Arizona, and Nebraska isn't entirely appropriate here, however, because Sun Health's and UNMC's approaches to curing Alzheimer's differ.

Sun Health looks more toward working with tissue already impacted by Alzheimer's, Gendelman said, while UNMC takes healthy tissue and "gives" it Alzheimer's in order to find ways to stop the disease before it begins. So UNMC wouldn't necessarily be looking to the same donor population for its rapid-autopsy program. In fact, three of the five rapid autopsies UNMC has reported performing so far have been on infant donors.

The UNMC trip to Arizona will be an intermediate stage in developing a rapid-autopsy program Gendelman hopes will be around for the long haul. His team consulted with people at Sun Health by telephone while starting the program, but the Nebraskans had a lot of groundwork to do on their own.

"We had to start a brand-new research program, totally from scratch, that involved a complex logistical network and, more importantly, a complex scientific network," Gendelman said.

The scientists at Sun Health will be able to offer experienced advice on how to enroll people in a brain-donor program. When research scientists approach a family whose loved one will die of a terrible disease, the scientists face a big challenge.

"The last thing that family is thinking of is donating a brain to science," Gendelman said. The Arizona rapid-autopsy team will help UNMC personnel understand how to approach grieving family members.

Another goal of the trip is to ensure the long-term viability of UNMC's rapid-autopsy program. Things have gone well so far, Gendelman said -- his research team has received enormous financial and logistical support from people in all levels at the medical center. "Virtually every person in this university has been phenomenal," he said.

But despite the program's achievements so far, basic arrangements still must be made. Where will the program get the long-term funding necessary to keep an autopsy team on call 24 hours a day, 365 days a year? How will the medical center gain the community support necessary for such a massive undertaking?

These are questions Gendelman hopes to get answers for not only in Arizona, but from Nebraskans when he returns to Omaha. Gendelman said he and the medical center are sincere in saying, "Look, we're in this together."

"It's our medical center," Gendelman said. "It's a medical center for all Nebraskans."

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This story originally appeared in Nebraska StatePaper on February 24, 2001.