NU Project to Boost Biotech Efforts, Save Money

LINCOLN - Three University of Nebraska campuses are joining forces to enable cutting-edge biological research and develop the state's biotechnology industry, while saving money through increased efficiency and cooperation.

A federal grant will fund the Nebraska Informatics Center for the Life Sciences, a one-stop-shop for the all the sophisticated tools and expertise needed in informatics. That's the scientific field that takes the reams and reams of raw data research scientists generate, and turns it into user-friendly information researchers can use to get the answers they set out to find.

For example, in genetics scientists can analyze changes in 15,000 genes at the same time, said Tom Rosenquist, vice chancellor for research at the University of Nebraska Medical Center.

"The volume of information that comes out of that is beyond the capacity of most people, of most systems, of most universities to analyze," Rosenquist said. But informatics holds a key to this problem because it lets the research scientists collect their data, while people trained in data analysis crunch the numbers and produce useful information that can lead to a new drug or new product.

No state funds will be required for the project. A $2.4 million National Science Foundation grant will fund the first three years, and more grants will be secured for operations after that.

Informatics requires powerful computers and specialized software. Duplication of these expensive resources at the University of Nebraska Medical Center, University of Nebraska-Lincoln and University of Nebraska at Omaha will be eliminated, and informatics experts at each campus will work together more than they have in the past.

"Definitely this can significantly promote research and education in the state by providing expertise that doesn't exist in any single university campus," said Simon Sherman, a UNMC professor who will direct the new informatics center. The deputy directors are Heshim Ali at UNO and Ruben Donis at UNL. About 40 professors from the three campuses are to participate, along with several faculty members from Creighton University.

The informatics center is expected to provide:

• Easy access to computer tools used in biological research, as well as databases containing the latest information about molecules of current interest to scientists


• Improvements to undergraduate, graduate and post-graduate education to prepare students for study and work in the biotechnology field


• Help for developing Nebraska biotechnology companies, by providing access to cutting-edge computer resources and information

The University of Nebraska Board of Regents is set to formally approve creating the informatics center at its Oct. 19 board meeting in Lincoln.

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This article originally appeared in Nebraska StatePaper on October 12, 2001.

Vaccine Tries to Keep Non-Hodgkin's Lymphoma in Remission

Editor's Note: This is the fifth story in a five-part series about clinical research at the University of Nebraska Medical Center. To learn more what clinical research is and the role it plays at UNMC, read the introduction to this series.

OMAHA - There's two places in the United States you can try an experimental vaccine made from your own tumor cells for one type of non-Hodgkins lymphoma: California's Stanford University, or the University of Nebraska Medical Center.

Choosing between the two was Jim Benson, an engineering professor from Kentucky. He's got stage four lymphoma, the worst stage; his cancer is in several lymph nodes in his neck and groin and has spread to his blood marrow. He wanted to be in a Phase II clinical trial for the vaccine, where all patients get the vaccine. That meant California or Nebraska. In Phase III trials, available at locations other than Stanford and UNMC, you could get the vaccine, or a placebo.

Nebraska, being closer to Kentucky, was the obvious choice because of the multiple trips he had to make for treatment and blood tests. He knew he could expect a short flight to Omaha, but didn't know the other benefit of seeing the nurses and doctors at the medical center.

"The level of empathy and concern, friendliness of the actual staff that's running the actual trial, is exceptional," Benson said recently from his room in the Lied Transplant Center, where he was resting after blood tests before catching a late-morning flight back to Kentucky.

Benson, 47, has follicular lymphoma, a common variety that makes up 15 percent to 20 percent of all non-Hodgkin's lymphoma cases. It's the one variety of non-Hodgkin's being targeted by vaccine trials, including one run by UNMC's Dr. Julie Vose. Non-Hodgkin's lymphoma is not a single disease, but a category of several closely related cancers of the lymphatic system. That's one of the most important parts of the immune system; it protects the body from disease and infection. A watery fluid called lymph contains white blood cells. The lymph flows through a network of vessels branching through the body, and filters through small organs called lymph nodes. When you're sick and get "swollen glands" on your throat under your jaw, those are some of your lymph nodes working to beat your illness.

How could a vaccine treat or cure cancer? Vaccines take a very small amount of a disease-causing bacteria or virus and put it in the body, where the immune system can practice defending the invader without being overwhelmed by a full-blown attack. The immune system "remembers" how to respond to that bacteria or virus. So when influenza, say, or diptheria attack the next time, the immune system can respond better and faster.

Turns out the immune system can be trained to remember and effectively attack follicular lymphoma, too. A company in California, Genitope, uses a patient's own cancer cells to make him or her a custom vaccine. It's a slow, painstaking process. First doctors take a biopsy, or sample, of a lymph-node tumor from a readily accessible spot -- say, under the arm. Using genetic engineering and cell cloning, the sample cells are modified slightly and joined with KLH, a substance found in mussels (a sea mollusk) to which nearly everyone's immune system responds. The patented technique takes six months to complete.

It's still ready in plenty of time. Clinical-trial patients go through a standard six-month course of chemotherapy treatment to put their cancer in remission, then rest for another six months while their immune systems recover from the poisonous onslaught of the chemotherapy drugs. Only then are they given the vaccine injection -- once a month for four months, then once more three months after the fourth shot. Patients receive two subcutaneous (just beneath the skin) injections in the same spot each time. One is the vaccine/KLH combination, another a protein called Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) that helps the body identify foreign substances.

Follicular lymphoma responds well to chemotherapy, going into remission in many instances. Unfortunately, it seems to always come back. The vaccine therapy being tested at UNMC aims to stop that, but it takes quite a bit of patience to work with this treatment.

"Since the patients take 10 years to relapse, you have to wait a long time to find out beneficial results," Vose said.

This Phase II trial of the follicular lymphoma vaccine is just one of three trials Vose is now running. The doctor's busyness has meant a wealth of opportunity for her assistant, nurse Susan Blumel. She finds potential trial participants, gets and keeps them enrolled, juggles insurance requirements and travel schedules, and writes frequent reports to the medical center's Institutional Review Board and the Food and Drug Administration. As if that were not enough, she also gives the vaccine shots.

Blumel, a certified clinical research coordinator, has had the opportunity to further her career by writing abstracts and giving talks about her and Dr. Vose's work. All the while, she gets to be right there at the patient-care level seeing real people get potentially life-saving treatment. Follicular lymphoma may be a very slow-growing cancer, but it still means death 7 to 10 years after diagnosis.

"It's very fulfilling working with patients on this level, because we're looking for better ways to treat lymphoma," Blumel said.

Blumel credits Vose with a knack for finding clinical trials that have a lot of potential. This trial, for example, adds on to the traditional regimen for treating lymphoma, yet holds very little extra danger for the patient.

"We're trying to prolong remission with relatively low risk," Blumel said.

Blumel has respect for the trial participants, who fly in from all over the country to see whether they can help themselves and people like them.

"These people are in remission," she said. "They could choose not to do anything. So the people that participate in the trial, I think, are future-lookers."

Benson, the Kentucky professor, looked to the future when he volunteered -- the future of lymphoma patients he'd befriended through support networks.

"That's one of the reasons we made the decision," Benson said. "Because even though they tout this disease as a 60-year-old disease (affecting people that old and older) … these people range from 31 years old to 51 or 53.

"If this can help anybody with that much life left, that's good thing."

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This story originally appeared in Nebraska StatePaper on July 27, 2001.

Tiny Radiation Beams Spare Cancer Patients Some Side Effects

Editor's Note: This is the fourth story in a five-part series about clinical research at the University of Nebraska Medical Center. To learn more what clinical research is and the role it plays at UNMC, read the introduction to this series.

OMAHA - With his throat cancer at its worst, Wayne Tobias couldn't even swallow water. After special radiation treatments available only one place in Nebraska, he's eating steak.

Even with his sense of taste deadened temporarily, Tobias has it better than many of the cancer patients who have gone before him. Because his radiation comes in hundreds of tiny beams aimed just at his tumor, he still has something most of us take for granted: saliva. He'd likely have a permanent case of dry mouth with traditional radiation.

He's also still got his voice, and just minutes after his latest treatment at the University of Nebraska Medical Center, he's happy to use it telling just how happy he is about eating steak again.

"It's about like getting my life back," he said. "Makes me think when I get my sense of taste back, I'm really going to enjoy that."

Tobias, 72, drives to Omaha from Hastings regularly to receive Intensity Modulated Radiation Therapy, a leap forward in cancer treatment available at just 80 hospitals nationwide, and just UNMC in Nebraska. The terrifically expensive and powerful machine doesn't aim a single-strength, wide beam of radiation at the tumor as in traditional therapy -- which hits and damages healthy tissue in the process. Instead, computers analyze a CAT scan of the cancerous area and figure out ways to fire hundreds of very narrow, but very powerful, beams that dodge critical healthy structures around the tumor. Like Tobias' salivary glands, voice box and -- most importantly -- his spinal cord.

"Our goal is always to deliver radiation where you can have better targeting, and spare more normal tissue," said Dr. Ken Zhen. He's one of the most experienced hands with the IMRT, having started using it in Iowa in 1998, just one year after the Food and Drug Administration approved it. He came to UNMC in 2000.

Zhen and his colleagues in radiation oncology are doing clinical research to determine how well the IMRT technique works. It's slow going; doctors need to wait 2-3 years to definitely see whether patients are cured, or suffer recurrences. Most of the data so far are on cancers in the head and neck areas, because it's easy to immobilize that part of the body. Just a tiny bit of movement can put that salivary gland you were hoping to avoid right in the path of a destructive beam.

Conversely, there's little data on using IMRT against moving targets -- such as the prostate gland, which shifts position based on bowel and bladder contents, even respiration. But another, even newer technology at UNMC is solving that problem. Called BAT, for B-mode Acquisition and Targeting, this new machine uses ultrasound imaging to find the prostate gland, then spits out a bunch of numbers that are punched into the treatment table to position the patient just so for his radiation therapy. In a great improvement for patient comfort, the ultrasound wand is applied externally to the lower abdomen, instead of inserted into the rectum.

Dr. Charles Enke is the main man with the BAT machine, which actually is all black with a big stylized bat-wing logo on the front. Men get a metal bat lapel pin when they complete their treatment.

"There is a significant amount of data emerging that indicates that the likelihood of prostate cancer control can be increased by 20 to 40 percent at 5 years by increasing the prostate dose over standard radiation doses," Enke said.

BAT works in concert with IMRT to help direct radiation beams around two critical structures near the prostate, the rectum and the bladder. The rectum's especially sensitive, and too much radiation can create a hole in it. That sentences patients to the inconvenience of a colostomy bag, external storage for the body's solid waste. Damaging the bladder can require an external bag to collect urine.

After treating 61 patients with BAT, Enke has found he can apply radiation doses of 7,600 to 7,800 rads, instead of the 6,800 to 7,100 rads many radiation therapy centers must use to avoid dangerous side effects.

Traditional therapy uses marks on the skin to indicate where the prostate was when doctors first located it and applied the initial radiation does. But preliminary results from a study Enke is conducting indicate the prostate may move as much as 10.4 millimeters from this location. Using the BAT machine, he's found, can reduce uncertainty about the prostate's location to 1 or 2 millimeters.

IMRT, with assistance from BAT in some cases, doesn't just make it possible to dodge healthy tissue. Doctors can also direct more powerful radiation at the tumor, the better to kill it faster. Think back to traditional radiation for throat cancer. Compared with IMRT, it's like putting fire hoses on both sides of your face and turning them on full blast. Sure, the tumor in the middle of your throat gets a full dose of radiation, but so do your salivary glands and spinal cord, because the radiation has to pass through those structures on its way to the spinal cord. So you have to limit the radiation sent to the tumor, because surrounding tissue can only withstand so much abuse. But with IMRT, which is like a very fine stream, you can send a tremendously powerful jet into the tumor because it's targeted to miss the parts you want kept alive. As the radiation emitter rotates around the patient, these tiny beams eventually stab through all parts of the tumor. (All this careful precision means IMRT treatment takes 30-40 minutes per treatment, while conventional therapy takes just 15 minutes.) If the fire hose and fine stream examples don't work for you, think of it this way: On a stage with 200 performers, you could light them all with one huge lamp. Or, you could use 200 spotlights , varying the color and intensity of each light to create a pleasing effect.

The idea behind IMRT therapy has been around for 20 years, Zhen said, but had to wait for computer technology to catch up with it. Medical physicist Ayyangar Komanduri explained that traditional radiation therapy can be planned with pen and paper, because there are just a few parameters to compute. But it's nearly impossible to analyze complex body scans and plot hundreds of precise coordinates without a computer's help.

"It's like trying to manage a bank account with several investors in place," Komaduri said. "How would you manage that without putting it into an accurate spreadsheet?"

For Tobias, the Hastings throat cancer patient, it's not just all this fantastic technology that's made the difference in his recovery.

"They've been wonderful people up here," he said. "They treat you like you're Warren Buffett or somebody."

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This story originally appeared in Nebraska StatePaper on July 26, 2001.

Rheumatoid Arthritis Treatment Pioneer Looks to Go One Better

Editor's Note: This is the third story in a five-part series about clinical research at the University of Nebraska Medical Center. To learn more what clinical research is and the role it plays at UNMC, read the introduction to this series.

OMAHA - The doctor who pioneered the most popular treatment for rheumatoid arthritis is at it again, using genetic analysis to find even better therapies customized to individual patients.

The University of Nebraska Medical Center's Dr. Jim O'Dell in 1996 published a landmark study in The New England Journal of Medicine showing a three-drug combination was more effective at treating rheumatoid arthritis than single drugs or two-drug combinations in use at the time. Now, he's testing new therapies using genetic samples taken from hundreds of participants in his many clinical studies.

O'Dell's aim: Know from the start which drug combination will work for a particular patient, instead of letting the debilitating disease march through a patient's body for as long as a year while doctors try different treatment approaches.

Rheumatoid arthritis is a disease where the body's joints deteriorate, causing pain and disability. It afflicts more than 2 million Americans.

The future of rheumatoid arthritis treatment is to stop giving patients the drug combination that works in 70 percent of people like them, and start giving them the combination that works in 95 percent of similar people, said O'Dell, who directs the five-state Rheumatoid Arthritis Investigational Network. Ideally, the chance of harmful side effects would be very low -- like 2 percent.

Existing therapies, as greatly improved as they are, work slowly. Doctors need at least 3 to 4 months each to see whether one's working -- meanwhile, damage could be spreading from the small joints of the hand to the large joints of the elbows and knees. A painful but bearable inconvenience that might be stopped at the hands could be allowed to proceed throughout the body, causing partial or total disability.

"If I have to utilize a year in finding out the proper course, then that patient's going to be paying for that 10 years later," O'Dell said.

O'Dell's key to quickly determining the right treatment is his database of data and genetic material from the people who have participated in his arthritis-drug studies.

"What Jim O'Dell has is the best sample population in the world," said the director of clinical studies who works with him, Geoff Thiele.

O'Dell has data on patients before and after treatment with a variety of drugs; people who responded and didn't respond to certain treatments; and on people who were in control groups and received a placebo rather than the drug or drugs being tested. With all this information in hand, he can look at 20 different factors in the blood that can influence whether a person gets rheumatoid arthritis. This gets down into some tiny, tiny minutiae. For example, O'Dell has discovered how to treat the small number of people who get a certain trait they could only have inherited if both their parents had it. People have to have a certain subset of a feature on their cells, out of many possibilities, to be susceptible to this kind of rheumatoid arthritis. But there's an advantage: O'Dell has already found the drug combination that works best for them, so they don't have to try a bunch of approaches before hitting the right one.

Thiele and his assistants work in the laboratory on genetic samples from the people who have participated in O'Dell's studies. That way, when they come up with a theory that a certain treatment strategy worked because of traits unique to some people in the study, they can test the samples to see whether those traits are indeed present.

Barb Counihan, diagnosed with rheumatoid arthritis in 1979, is somewhat of a walking history of arthritis care. She received injections of gold (that's right, the metal) for 14 years, then took the steroid prednisone, then methotrexate and aspirin, and finally O'Dell's three-drug combination. She's been participating in O'Dell's clinical studies since 1995.

Counihan, an accountant at KMTV in Omaha, said she's grateful that world-class treatment for her arthritis can be found a short trip across town.

"Terrifically, immensely grateful for that," she said. "You don’t have to travel to another major city to get care."

She's also glad that while she's getting the best treatment for herself, her body's reaction to the drugs is helping doctors understand how similar people will fare.

"I'm excited that I can be a part of that study, and help patients in the future," she said.

O'Dell's next step is to compile a national database of rheumatoid arthritis patients, to put together on a large scale what he's done on a small scale. The larger the sample size, the more accurate the results. He's working now to get a National Institutes of Health grant for the effort.

"I could go and take 500 patients who responded to one treatment, 500 who didn't, and see if there's a common genetic trait," O'Dell said.

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

Versatile Tiny Bubbles Hold Promise Throughout the Body

Editor's Note: This is the second story in a five-part series about clinical research at the University of Nebraska Medical Center. To learn more what clinical research is and the role it plays at UNMC, read the introduction to this series.

OMAHA - In the hands of Dr. Tom Porter, miniscule bubbles smaller than red blood cells can make the heart beat normally again, test blood flow to that organ, break up blood clots and deliver drug treatments with microscopic precision.

They're called microbubbles, and they're versatile little things. Just four or five millionths of a meter in size, they can carry drugs inside or on their surface. When doctors intentionally break them inside a patient's body with ultrasound waves, their tiny explosions can shear off bits of clots blocking arteries. Not only are they effective, but every application of them is easier on the patient than the standard treatment they may one day replace.

The microbubbles are being used in two human clinical trials at the University of Nebraska Medical Center right now: terminating heart-rhythm disturbances and breaking up clots in renal dialysis grafts. The first use could reduce the need for electric shocks to pace the heart, and the second use could fix a complication patients experience when undergoing kidney hemodialysis.

The bubbles are a protein shell with a gas inside. They first contained air, but Porter and his team determined they'd hold up better filled with denser gases like fluorocarbons. UNMC makes its own bubbles with ultrasound waves.

"Ironically, it's ultrasound that creates the bubbles and that destroys them," Porter said.

This destruction seems to be able to act like a pacemaker to restore normal heart rhythms. There are many different abnormal heart rhythms, which can be dangerous. Some traditional ways of treating abnormal heart rhythms are external shocks and internal pacemaker devices. Patients must be sedated to receive external shocks, while inserting a pacemaker requires surgery. Microbubbles can be injected like medication, and manipulated with harmless ultrasound waves like the ones used to view a developing fetus inside a pregnant woman.

"In essence, it's simplifying the process and making it safer for the patient," Porter said.

Small waves are created when ultrasound makes microbubbles expand and then suddenly collapse. These waves seem to be able to pace the heart into normal rhythm, Porter has found. The waves also can erode the surface of a blood clot in an artery, such as one leading to the heart. One of the traditional ways to deal with arterial blood clots is by inserting a ballon into the artery and inflating it. But this technique can damage the artery, leading to the formation of scar tissue that can just exacerbate the blockage.

If this balloon insertion procedure, called balloon angioplasty, has already occurred, microbubbles can prevent additional blockage from developing. They can carry a special gene therapy to the precise problem area of the artery and at that spot, and only that spot, block a protein that can cause further narrowing of the artery.

"If we give a gene … we only want it to work in one area of the body," Porter said.

Clots can also be troublesome in patients undergoing hemodialysis. In this procedure, a person's blood is filtered through an external machine, instead of by the kidneys. A common way to extract the blood and then reinfuse it is through an arterial-venous graft. In a surgical procedure on the arm, doctors graft together an artery, which takes blood out to the body from the heart, and a vein, which returns blood to the heart. So blood flows into the artery, out into the dialysis machine, and then back into the vein.

Sometimes this graft between the artery and vein can get blocked with a blood clot. That can mean another surgery to create another graft elsewhere on the arm. Because these grafts take a long time to heal before they can be used for hemodialysis, it's more than just a little inconvenient to get a graft clot.

Enter the microbubbles again. Porter has a Phase I clinical trial going to determine whether they can break up clots so patients can continue using the same graft, and don't need more surgery to create a new one. He'll have to overcome some challenges to make this work; one of them is preventing small pieces of clot from traveling into smaller blood vessels and blocking them, which would create new and potentially more serious problems.

Microbubbles' ability to deliver drugs to specific locations could greatly improve chemotherapy for cancer. Chemotherapy drugs are powerful poisons used to kill cancer cells. But they must be used with extreme caution because they're toxic to healthy cells, too. Spilling one kind of chemotherapy on bare skin while trying to inject it into the body, for example, can eat away the skin. But if these poisons were contained inside microbubbles and released only when they reached the tumor, side effects from chemotherapy could be reduced.

Working closely with this cutting-edge research for three years has been Porter's assistant David Kricsfeld, who will take an already bulging resume with him when he starts medical school next month.

"A lot of investigators, when we go to these national meetings … they're amazed at how we have all these applications of microbubbles going on at once," Kricsfeld said.

What makes this possible is Porter's drive and intelligence, Kricsfeld said.

"Who would have thought that this may help break up blood clots, or help deliver drugs?" he said.

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

Clinical Research Turns Laboratory Ideas into Reality for Patients

OMAHA - Basic medical research like sequencing the human genome and transforming stem cells into blood, bone and brain tissue makes headlines because the ideas involved are so new, so cutting-edge, so "Gee whiz!" But at research hospitals across the country, including the University of Nebraska Medical Center, it takes clinical research on volunteer subjects to determine whether the latest big idea can help real human beings.

In a five-part series beginning today, StatePaper will tell you about the clinical research that makes up almost a third of the externally funded science UNMC does each year. You'll learn about doctors testing:

• A popular anticoagulant drug (also known as a blood thinner) to see whether it can safely be given in small doses over a long term to prevent recurring blood clots


• "Microbubbles" manipulated with harmless ultrasound waves that can pace the heart, deliver medications with pinpoint accuracy and break up clots


• Patient-specific rheumatoid arthritis treatments which could more quickly halt that debilitating disease's march through the body


• Machines that use pinpoint precision to safely deliver higher levels of cancer-killing radiation than ever before possible


• A vaccine made from patients' own tumor cells to prevent the recurrence of non-Hodgkin's lymphoma

"Clinical research is critically important because it does apply the knowledge gained (through basic research) at the bedside," said Dr. Harold Maurer, chancellor of the medical center.

Dr. Tom Rosenquist, interim vice chancellor for research, explained the difference between basic and clinical research.

"The basic science research addresses sort of fundamental questions about the biology of cells and tissues and genes and DNA those kinds of things that we predict may have some value for disease prevention or treatment. But you don't know ahead of time," Rosenquist said.

Out of that basic research can come ideas for new drugs.

"Most of the clinical research that we do here relates to either drugs or methods of applying the drugs to various diseases," Rosenquist said. "… [R]esearch that you apply directly to human beings to see if you get any improvement in their disorder."

Clinical trials are usually funded by pharmaceutical companies or medical equipment manufacturers, which want to find out whether their latest inventions are useful. Volunteers get the trial treatment and any associated examinations, like blood tests, free of charge from the company. But patients and their insurance companies are responsible for the costs of other care. For example, in the non-Hodgkin's lymphoma vaccine study you'll read about in Part 5 of this series, patients are responsible for undergoing a six-month course of chemotherapy before receiving the trial vaccine.

There are three stages of clinical research:

• Phase I: A very small trial where the drug is given to perhaps a dozen patients who have terminal diseases and are not expected to survive. Patients agree to take the new drug without any expectation that it will help them, although it might. At this stage, scientists want to know whether the drug has harmful side effects. Healthy people may also take very small amounts of the drug to determine its toxicity.


• Phase II: Participating at this stage are a small number of patients, perhaps 50, who haven't had luck with existing treatments. This trial determines not only whether the drug is safe for humans, but whether it's effective at treating the targeted medical condition.


• Phase III: Thousands of patients at sites across the country may participate at this stage, which tests the effectiveness of a drug over a long period of time.

Rosenquist said it's usually easy to recruit volunteers for each phase.

"I think the reasons that the seriously ill patients want to participate are pretty self-evident," he said. "Those who are not convinced they may derive any benefit themselves are doing this out of a sense of duty to their fellow man."

That’s the same motivation for many in Phase II and Phase III trials.

"It makes you feel to good to participate," Rosenquist said.

UNMC values each of the volunteers who work with the dozens and dozens of trials going on at any one time.

"They're indispensable. Absolutely. Nothing can be done to advance the science without them," Rosenquist said.

Maurer agreed. "Without them, without the patients participating, there would be no research," he said.

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This story originally appeared in Nebraska StatePaper on July 23, 2001.

Medical Mechanic Haire Maintains the Body’s Highways

Editor's Note: This is the first story in a five-part series about clinical research at the University of Nebraska Medical Center. To learn more what clinical research is and the role it plays at UNMC, read the introduction to this series.

OMAHA - Mechanic and medical researcher Dr. William Haire is approaching dangerous blood clots in the body somewhat like the way a street maintenance engineer approaches potholes in the road.

While the engineer wants to use as little patching material as possible to plug the holes in the road, Haire wants to use as little medicine as possible to control the clots that plug up blood vessels and can kill. The engineer's aim is to stretch the city's always-limited maintenance budget. Haire wants to make a good clot-busting drug, Coumadin, work even better by finding the lowest effective dose -- one that keeps harmful clots from forming, but prevents the bleeding complications that make the therapy tough to manage. Coumadin has a narrow therapeutic range. There's not much wiggle room between a dose that's helpful, and a dose that's harmful.

When he's not treating patients for the common medical conditions of deep-vein thrombosis (usually, clots in the leg) and pulmonary embolisms (a clot that affects the lungs), Haire can be found working in his garage restoring 1946-1948 Plymouth automobiles. Or, he might be designing album covers and stage props for local rock bands. These mechanical and artistic hobbies help him think about new ideas for practicing medicine.

"The body is nothing more than just a very, very complex machine. But it takes an artistic, kind of out of the box approach, to understand some of the subtle complexities of this machine," he said.

Haire's penchant for the complexities of blood clots won him a role in a National Institutes of Health study of the popular anticoagulant drug Coumadin. He's known nationally for his work with blood clots. The affable Haire wouldn't volunteer this information, but when asked he'll confirm that he's one of a very few University of Nebraska Medical Center researchers ever asked to write two guest editorials for the prestigious New England Journal of Medicine. Both were on blood clots, a passion of Haire's and a national health problem. About 500,000 Americans a year develop deep-vein thrombosis -- a blood clot in one of the body's large veins, usually in the leg. Pieces of these clots can break off and travel all the way to lungs and block that organ's tiny capillaries. That's called a pulmonary embolism, and can be fatal. About half the blood clots patients suffer are ideopathic, meaning doctors can't find a cause.

It’s these ideopathic blood clots that concern Haire and researchers at 60 other sites nationwide. Paul Ridker of Brigham and Women's Hospital in Boston, principal investigator for the study, said he looked for the top scientists across the country when setting up the project.

"And obviously Bill was one of those people," Ridker said.

The PREVENT study, as it's called, is fairly simple and quite convenient for participants. Patients who have been on long-term anticoagulant therapy with Coumadin get to stay on the drug for free, at a lower dose the researchers hope proves effective. Blood testing is needed just once every two months, and the testing machine is portable so study participants need not leave their home or work.

Some of these ideopathic clots run in the family and can recur over a patient's lifetime. By joining the study, participants can help themselves avoid future clots, and perhaps be of aid to their families as well.

"So Grandpa may be helping to answer questions that will be helpful to grandson or granddaughter," Haire said.

That chance to help others helped motivate Robert Volz to join the Coumadin study.

"It appears there's very minimal risk for doing it, and yet the outcome could be very beneficial," Volz said.

Doctors diagnosed Volz, vice president for facilities at Ameritrade in Omaha, with a deep-vein thrombosis of the right leg after he had taken just a one-hour plane ride to Denver. After six months on the standard Coumadin treatment, Volz wondered what should be his next step for preventing a second blood clot -- especially since doctors couldn't exactly place the cause of his first one. His doctor said he didn't know the best long-term option -- but there was a study at UNMC trying to find out.

Taking his traditional Coumadin treatment, Volz had to drive from Ameritrade in west Omaha to UNMC in central Omaha first weekly, then monthly, for blood tests. Now on the Coumadin study, someone from the medical center drives out to Ameritrade. A finger prick and five minutes later, it's goodbye for another two months.

"That's as good as it gets," Volz said. "It's awfully nice where someone's coming to you."

Haire's assistant John Schneider, a first-year medical student, is often the one driving out and doing the finger-pricking. Besides the scientific knowledge, Schneider said, he's gaining important experience dealing with all kinds of patients. He works with everyone from vice presidents like Volz to blue-collar mechanics. It's a big leg up for medical school, he said.

"Being exposed to that, I think, has really benefited me," he said.

Looking at what doctors now understand about blood clots, and what they hope to learn, is fascinating stuff. Think of the body's blood vessels like a road network, Haire says. The body's natural processes have blood vessels breaking all the time, and quickly sealing up when the blood clots as it should. This is like roads developing potholes that the roving street maintenance crew quickly fills (well, maybe not as quickly in some cities as in others). Clots also form when the body's injured; say, by a cut. Clots keep you from losing a lot of blood because they plug the hole from which the blood is leaking. It's when the natural clotting process gets out of control that problems start to occur. Then, clots can form where there are no holes to plug -- again, most often deep in the veins of the leg.

Conditions like trauma, serious illness and pregnancy can all lead to these harmful blood clots. What doctors have found in the past five years is that patients who get a clot tend to be at risk for another clot. So now they need to figure out exactly what this risk is, and whether there's a dose of the anticoagulant drug Coumadin that can be used long-term to prevent more harmful clots, while still keeping the blood's beneficial clotting tendencies around. If the balance isn't kept just right, and a patient's blood doesn't clot readily enough, he can bleed too much -- which leads to organ damage, organ failure and even death.

"It's a problematic medicine in that it's effective, but it's difficult to safely control over a long term," Haire said.

That blood testing we've been talking about is to measure a patient's prothrombin time, which means the time it takes his or her blood to clot. The term's usually shortened to "pro time," and the value is measured in units that go up or down from 1.0, which is the average clotting time for a human. When doctors are treating a blood clot with Coumadin, they're usually aiming for a pro time of 2.0-3.0, which means the blood is clotting two to three times slower than normal. The Coumadin study at UNMC wants to see whether a pro time of 1.5 can still be effective. Maintaining that kind of a pro time requires less Coumadin, so patients stay farther away from the "knife edge," as Haire puts it, between the drug's helpful and harmful dosages.

Coumadin and other anticoagulants, by the way, are not blood thinners -- even though doctors and nurses sometimes call them that to keep things simple for patients. Such drugs don't thin the blood, that is, change its viscosity. In fact, Haire said, only with some rare conditions does the blood's viscosity change. And anticoagulants don't prevent clotting outright, they simply slow down the process so the body can get it under control. Clotting is out of control when a clot forms somewhere other than where the bleeding problem is.

"If you will, (treatment with anticoagulants) is like adding a governor to your engine to make sure the engine can't go too fast," Haire said.

There's a tendency to blame bleeding complications solely on Coumadin, but people who do so forget that in order to bleed, there needs to be a hole in some blood vessel. In most bleeding incidents with Coumadin patients, a condition unrelated to the drug caused the bleeding -- such as a duodenal ulcer, a colonic polyp, or a kidney stone. Say a kidney stone scratches a person's ureter, and the bleeding doesn't stop fast enough because the Coumadin he's taking has slowed the clotting. The patient sees blood in his urine, and blames it on the drug.

"But did the Coumadin cause the bleeding? No," Haire said.

But the bleeding's still a problem, especially in older patients who are at the most risk for blood clots. They often have underlying diseases and weaker organs, both related to aging, that make it less likely they'll survive losing a lot of blood. That makes it even more important to find a long-term dose of the drug that can stave off dangerous bleeding complications.

One notable aspect of the entire PREVENT study is the diversity of its participants. While many clinical studies consist mostly of white men, PREVENT has almost half women, and 19 percent minorities. Haire has plenty more room for volunteers in the Omaha program, and he'd be glad to take calls from interested people at (402) 559-7599.

"I'll take a hundred more next week," Haire said.

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This story originally appeared in Nebraska StatePaper on July 23, 2001.

Leukemia, Lymphoma Patients Sought to Test 'Mini-Transplants'

LINCOLN - The University of Nebraska Medical Center needs 40 cancer patients to help test a new "mini-transplant" procedure researchers think will be far less toxic than traditional allogenic bone-marrow transplants.

The technique developed by Drs. Steven Pavletic and Greg Bociek aims to reduce the risk and side effects of graft-versus-host disease - a potentially fatal side effect of allogenic transplants. In traditional transplants, bone marrow from related and unrelated donors is used to create a new, cancer-free immune system in the patient. The UNMC technique transplants bone marrow only from related donors, and uses much lower doses of radiation and very mild chemotherapy. Bone marrow is the source of the body's white blood cells, the immune system that fights infection.

Think of it this way: You've got two overlapping circles, with the patient standing in the middle of the overlap. One circle represents "graft vs. cancer," the good outcome doctors are looking for where donor bone-marrow cells attack the patient's cancer. The other circle represents "graft vs. host," the bad outcome doctors hope to avoid where donor cells attack other tissues in the patient's body. By carefully balancing transplanted cells, radiation and drug treatment, the UNMC doctors hope to have the patient touching as much as possible of the good circle and as little as possible of the bad circle.

"Our protocol is designed to be very non-aggressive," Pavletic said.

The UNMC approach also involves a new use for an old leukemia drug, pentostatin. "The drug plays an important role in suppressing the patient's immune cells during the transplant process," Pavletic said. This is another key thing to understand about the mini-transplants. Previously, doctors have used heavy doses of radiation and chemotherapy to essentially destroy a patient's immune system, so there will be a clear path for the foreign donated bone-marrow cells to do their work and not be rejected by the patient's own immune system. With mini-transplants, it's only necessary to suppress the patient's immune system -- putting him or her in far less danger of complications.

Those eligible for the study include patients who are responding to standard treatments, but whose disease is at a high risk of coming back; patients older than 60; those who can't tolerate high doses of radiation and chemotherapy; and those whose cancer returned after an autologous stem-cell transplant.

"We use this therapy with patients who otherwise have very little hope. Instead of no chance for survival, we hope we can achieve a 30 to 50 percent cure rate. We want to find something for these patients," Pavletic said.

For progress on cancer therapies to continue, Pavletic said, people need to continue to enroll in clinical trials like the one UNMC plans. He cited the Food and Drug Administration's recent unusually rapid approval of Gleevec, an oral therapy for some patients with chronic myeloid leukemia. Pavletic was the principal investigator for UNMC's portion of the national Gleevec study.

"The approval of Gleevec in two years was the most rapid FDA approval ever," Pavletic said. "This is one of the reasons why it is important for patients to participate in clinical trials.

"If we didn't have patients, we wouldn't have any of this information yet. Some people have reservations about participating in clinical trials like 'I'm going to be a guinea pig,' and so on. It's natural to have these reservations. But all these trials are therapeutic.

"The bottom line is we are doctors. We don't offer a trial if we think there is something better."

For more information about the study, call Karen Taylor at (402) 559-6729.

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This story originally appeared in Nebraska StatePaper on

UNMC Scientists Seek Patent for Potential Parkinson's Vaccine

LINCOLN - A University of Nebraska Medical Center research team including Dr. Howard Gendelman and a star graduate student are awaiting a patent on what could be a vaccine for Parkinson's disease.

Gendelman discussed his and graduate student Eric Benner's Parkinson's discoveries Wednesday at an Omaha seminar hosted by Nebraskans for Research. It was the first time Gendelman had publicly discussed the matter since December, when StatePaper exclusively reported limited details about the potential vaccine.

"This is kind of the first comprehensive effort to tackle Parkinson's research in this way," Gendelman said.

Parkinson's disease, a degenerative brain disorder, afflicts more than 1 million Americans with muscle stiffness, tremors, slowness of movement, poor balance and walking problems. Actor Michael J. Fox and former Attorney General Janet Reno have the disease.

Few new details about the potential vaccine beyond what StatePaper has already reported were available Wednesday. Gendelman said he must keep quiet about specifics or risk losing the patent. (As with all patents, approval isn't a sure thing.)

Unfortunately, things that must be kept quiet include how the vaccine would work, and on what kind of patient.

"The crux of how the vaccine works is all under patent," Gendelman said.

But Gendelman was able to release these new points of interest:

• If the patent is approved, proving the concept behind the potential Parkinson's vaccine will take about five years. Laboratory work on cell cultures is already underway. Experiments on mice that have been given a Parkinson's-like condition could begin soon. The timetable for human trials will depend, as always, on the Food and Drug Administration.


• The illegal trade in the street drug heroin actually has a positive side effect. A chemical used to purify heroin -- methylphenyltetrahydropyridine, or MPTP -- gives mice a condition close enough to human Parkinson's disease to be useful for research.


• Cells from aborted human fetal tissue are not being used in the Parkinson's vaccine research. (Gendelman uses fetal cells in other research projects.) If fetal cells were used in the vaccine research, Gendelman said, they would be used to prove the vaccine works, not to manufacture the vaccine itself.

As StatePaper reported in December, the research into the potential vaccine got started with Benner's idea to use a vaccine to get immune cells, called T-cells, into the area of the brain affected by Parkinson's. Once in the damaged environment, these T-cells actually secrete chemicals that reduce the damage that's occurred. For reasons that are still unknown, these T-cells only do this in damaged areas, not healthy ones.

Collaboration between Gendelman, Benner and scientists in New York and Israel has been key in developing the ideas behind the potential vaccine. Benner has worked with the renowned Movement Disorders Division at Columbia University's Columbia-Presbyterian Medical Center in New York. Gendelman's contributions come in part from his Fulbright Scholar experiences studying spinal-cord regeneration at the famous Weizmann Institute of Science in Israel. Gendelman's ideas on the potential vaccine also are an outgrowth of his "Dr. Jekyll and Mr. Hyde" approach to other degenerative brain disorders like Alzheimer's disease and AIDS-related dementia.

You can read more about Gendelman's theories in this story, but here's the gist. Gendelman says brain cells called glia, in the vast majority of cases, act like the good Dr. Jekyll, helping the brain function. But sometimes the glia can be transformed into the evil Mr. Hyde, hurting the brain. In the classic story, the evil persona isn't permanent - Mr. Hyde turns back into Dr. Jekyll. The analogy to that story is fitting, because Gendelman's research has found ways to turn the evil glial cells back into good ones.

Also notable in this is the rarity of having a graduate student join a world-renowned researcher as co-discoverer of a patent. Even in the unlikely event the patent isn't approved, just being listed on the application will be one heck of a resume booster for Benner.

"He's unbelievable. We let this kid roll and he's performed spectacularly," Gendelman said. "He had a significant role in the discovery."

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This story originally appeared in Nebraska StatePaper on May 30, 2001.

$3 Million Grant Boosts Rapid-Autopsies Effort

LINCOLN - Dr. Howard Gendelman has received a prestigious national grant award that will help his University of Nebraska Medical Center research team continue developing rapid-autopsy techniques for brain-disease treatment.

The $3 million Javits Neuroscience Investigator Award is the second major award Gendelman has received in a year. Last March, Gendelman was named a Fulbright Scholar and studied nerve regeneration for eight months at the world-renowned Weizmann Institute in Israel.

Javits winners make up a rather exclusive club. One of last year's Nobel Laureates in medicine, Paul Greengard, received the award in 1985.

Gendelman's research center is one of just a handful in the world pursuing rapid autopsies as an alternative source of brain tissue for research into Alzheimer's disease, Parkinson's disease and AIDS-related dementia. UNMC launched a search for alternatives after controversy erupted 16 months ago over Gendelman's use of aborted fetal tissue in his brain-disease research. Anti-abortion activists who think the research encourages abortions have lobbied the Nebraska Legislature to ban the use of aborted fetal tissue. A ban proposal failed last year, but a similar one is pending this year.

Gendelman said the Javits Award represented crucial national recognition and validation of his rapid-autopsy efforts, which he began a relatively short time ago in February 2000. When he was under consideration for the award last year, he said, the program he'd built from scratch was in its infancy.

"If I don't get the money at the national level, this research ends," he said.

Rapid autopsies performed within an hour of brain donors' deaths have yielded two of the three types of brain cells required in Gendelman's research. Gendelman and just a few other scientists have managed to derive viable astrocytes and microglia, two types of brain-support cells, from rapid autopsies. But the brain's all-important "thinking" cells, the neurons, have so far eluded everyone. Gendelman returned to Nebraska this week from Arizona, where he and his research team studied rapid-autopsy techniques at the science center that pioneered them, the Sun Health Research Institute.

A national committee of scientists reviewed Gendelman's entire body of work, rapid-autopsy efforts included, and decided to fund it for an unusually long length of time -- seven years. Grants other than the Javits Award normally don't run longer than five years.

"It puts a stamp of approval that we trust the quality of his research enough that we believe he will continue to be productive over the next seven years," said Al Kerza-Kwiatecki, program director for infectious diseases of the nervous system at the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health. His institute administers the awards.

Kerza-Kwiatecki continued: "That's quite a benefit to give a scientist this kind of vote of confidence, as it's very time-consuming to make scientists submit new documentation every couple years so their progress can be monitored."

UNMC Chancellor Dr. Harold Maurer congratulated Gendelman and his research team. "I think the Javits Award sends a strong message that UNMC is making impressive strides in its research efforts on neurodegenerative disorders," Maurer said. "It is among the best in the nation, and we are very proud of this accomplishment. The fact that a large portion of the proposed work will come from alternative sources other than fetal cells demonstrates the commitment and progress made by our scientists."

The $3 million Javits Award doesn't end the financial challenges facing UNMC's practically brand-new rapid-autopsy program. The Javits grant fund scientific experiments on the brain tissue obtained from rapid autopsies, but does nothing to help in the extremely expensive and time-consuming process of conducting the rapid autopsies. The logistics are challenging; because brain donors don't always die during business hours, a large team of doctors, nurses, technicians and scientists must be kept on call 24 hours a day to collect brain tissue on a moment's notice. (For more on the challenges involved, see StatePaper's article "Rapid Autopsies the Tool in Arizona, Nebraska Quest for Neurons.")

UNMC has already spent $400,000 on developing the program, but more money is needed to fund the ongoing logistical needs. Gendelman said he's applying for other national grants to that end, and other fundraising efforts are still under discussion.

In 1983, Congress created the Senator Jacob Javits Awards in the Neurosciences. They were established to honor the late Sen. Jacob Javits of New York, who suffered from Lou Gehrig's disease. Awardees must have demonstrated exceptional scientific excellence and productivity in one of the areas of neurological research supported by the National Institute of Neurological Disorders and Stroke, have proposals of the highest scientific merit, and be judged highly likely to be able to continue to do research on the cutting edge of their science for the next seven years.

Gendelman said everyone at his research center, and people like the UNMC chancellor and University of Nebraska president who supported it, deserved credit for the Javits achievement. "Any award of this nature is never a single person. I would love to take credit for everything I do. But the truth is this is an award for our entire team, this research center.

"It's the team, again not me, who's turned the adversity into triumph. I couldn't be more proud of the people who have worked with me."

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This story originally appeared in Nebraska StatePaper on March 10, 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.

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.