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Brain tissue for research: the need is there.

Brain Tissue for Research: the Need Is There

The nation's dwindling supply of brain and spinal cord tissue used in research is a source of growing concern. Donated by people with MS (as well as by healthy people), these postmortem tissues are crucial to the work of MS investigators around the world. Their supplies come from many sources, among them tissue banks such as those supported by the National Multiple Sclerosis Society.

One such major facility is the National Neurological Research Bank in Los Angeles, funded for many years by the Society as well as other agencies. Director Wallace Tourtellotte stores frozen tissues covering at least 15 different kinds of neurological or psychiatric diseases. He ships brain, spinal cord, spinal fluid and blood samples free of charge to scientists who have a bona fide need for such samples in their research. He also uses the material for MS research in his own laboratory.

A substantial number of major findings have emerged over the years from studies of frozen tissues. Dr. Tourtellottee ticks them off: the discovery that patients with Parkinson's disease lack dopamine, a chemical messenger that transmits nerve cell signals in the brain, which led to the development of a new therapy; the finding that there is a 90% decrease in chlorine acetyltransferase in the brains of Alzheimer's disease patients; the disclosure of certain immune T cells in the inflammatory lesions in the brains of MS patients, linking the cells with active extension of the lesion; and the finding of measles virus in the brains of MS people (as well as in some healthy persons). In Dr. Tourtellotte's own laboratory, Dr. Shozo Nakamura from Sendai University in Japan is investigating viral nuclei acids, using special hybridization techniques on MS brain samples.

The L.A. bank currently has about 130 MS brains in storage at the VA Wadsworth Hospital where it is based. "There's a population of 11 million people living within 100 miles of our bank," Dr. Tourtellotte notes. "We can get tissue from any one of them within two or three hours after we're notified. For some investigators this is extremely important, because what they~re working on must come from fresh samples. Nucleic acids and other biochemicals degrade rapidly within a few hours of death."

On the other hand, the neurologist doesn't turn down any offers of brain tissue, even if it takes nine to ten hours to transport it. Much work can still be done on such samples.

Potential donors can enroll in the program through a "Gift of Hope." After their death, brain and spinal cord tissues are removed quickly by experts. The first examination done on the tissue confirms the clinical diagnosis of MS; findings are sent directly to the patient's family.

In Englewood, Colorado, another tissue bank has been in operation since 1976. This is the Society-funded Rocky Mountain MS Center Tissue Bank, directed jointly by Drs. Jack Burks and Ronald Murray. It is somewhat different from the L.A. bank in that it focuses exclusively on MS donor tissue (and healthy tissue), not material from people with other diseases. The bank has now accumulated brain and spinal cord samples from 160 donors with another 247 prospective donors signed up. These range from such states as Colorado, Nebraska, Utah, Kansas, Georgia, Wyoming, Connecticut, Missouri and Texas.

To get the tissues within six hours at the latest -- considered the critical parameter -- the bank has enlisted the help of the Governor's office and the Civil Air Patrol, whose members within a seven-state area donate their flying time. Commercial airlines, ambulance companies and pathologists have also given time and services to ensure speedy delivery of the tissues.

The Colorado researchers use the tissues in their own labs to study the distribution of immune cells within areas of demyelination and to look for infectious agents -- especially viruses -- that might trigger an immune response.

This bank's tissues are also used by outside institutions here and abroad. Once, when scientists reported finding traces of the HTLV-1 virus in MS patients, another group at the Pasteur Institute in Paris called the Rocky Mountain MS Center asking for brain tissue to use in checking out the finding. The tissue was immediately sent to Paris, a few weeks later the Pasteur team had done the experiment, and the results were reported in Nature within a few months -- breakneck speed, for science publishing.

Drs. Murray and Burks are planning to take blood samples from patients who have agreed to be donors later. Dr. Murray explains: "We want to be able to analyze their white blood cells for the presence of any viruses that may be there now, or for any immune dysfunction. We hope to generate a DNA bank on these patients, too. We plan to have complete profiles on them during the active phase of their disease. We may then correlate this with the tissue obtained later. It will be most helpful to us in analyzing the course of the disease."

Dr. Burks often addresses MS groups, soliciting their cooperation in donating brain tissue. At first, he says, he was a little uncomfortable doing this, but then he discovered the patients were much more at ease than he was. They seemed uniformly eager to contribute something personally to MS research.

A Philadelphia tissue bank that uses all donated tissue for its own research is at the Wistar Institute. There, a group of 18 virologists, immunologists and neurologists working under the direction of Dr. Hilary Koprowski are trying to isolate a virus from tissues of people with MS. They are operating on the theory that MS is caused by a slow-acting virus that enters a person before the age of 15 and is activated later in young adulthood. Alternatively, the disease may itself be a delayed reaction to a common virus.

The Wistar scientists collaborate with a group at the University of Pennsylvania, which has a 33-year old MS clinic. Together the two institutions have created an MS Research Center. Here, a search has been continuing for the presence of the HTLV-1 virus in MS tissues. Quantities of brain tissue are needed for this work. "We really don't know which brain is going to be the key to the riddle of MS," says Dr. Lucy Rorke, neuropathologist who aids the tissue bank. "We are finding out very interesting things in our research, even though the cause of the disease still eludes us. The important point is that we are constantly developing new techniques for studying tissues. The more we have to work with, the more valid our conclusions are going to be."

She concedes that research projects don't always turn out as expected. One early study conducted by Wistar proved no exception. Previous work with other virally induced diseases had suggested it was possible to reproduce aspects of MS in experimental animals by injecting brain cells from MS patients into them. This was done over several years at the Southwest Medical Foundation in San Antonio.

"The bottom line was that we never succeeded in producing anything like MS in these animals," says Dr. Rorke. "The problem may be that we didn't wait long enough for something to happen. Since the animals did not develop MS, the project was terminated."

Healthy brain tissue is the battle cry of Dr. Edward Bird, who runs the McLean Hospital Brain Tissue Resource Center in Belmont, Massachusetts.

"Most people don't think their brain is of any use after death," Dr. Bird comments. "But of course they're wrong. It's very valuable. One small piece of tissue can be distributed among 100 different investigators. So brain donations go a long way."

The neurologist was so concerned about the tissue shortage that he co-authored a letter with Dr. Edward Stopa to the January 5 New England Journal of Medicine calling for contributions from fellow doctors. He wrote that although healthy brains had made up 20% of all donations to the bank during its first five years, they have now dropped to an "alarming" level of 3%. Ironically, he added, this shortage of "control" brains seemed to be occurring at a time when requests for such tissues have increased substantially.

Calling for fellow physicians to "consider seriously the possibility of donating their brains for research after death," -- establishing a trend for others to follow -- he also noted that an ample supply of human tissues might reduce the need for many studies now performed on laboratory animals.

Dr. Bird, who established England's only tissue bank at Cambridge, believes that Americans are more loath than Europeans to donate brain tissue. "They readily donate their kidneys or livers or hearts," he said, "but they seem to have some reluctance to part with their brains." He adds, "I think it's very important to educate people about the tremendous advances being made in neurological disorders by scientists who depend completely on brain tissues that have been donated by people who care about future generations."

Dr. Tourtellotte of Los Angeles puts it more succinctly. "Everybody has to die. I have to. What better way to do it than to make a precious resource -- your brain -- available to future generations? I tell my MS patients they certainly don't have to donate their tissues if they don't want to. But they should at least consider the possibility. They should know we're here."
COPYRIGHT 1989 National Multiple Sclerosis Society
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Copyright 1989, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Title Annotation:includes information on how to donate brain tissue
Author:Shaw, Phyllis
Publication:Inside MS
Date:Sep 22, 1989
Words:1552
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