January 3, 2006             (Chicago Sun-Times)

BY JIM RITTER Health Reporter

Doctors see benefits, but also fear public ‘yuck factor’

Medical researchers are expressing a growing interest in studying a surprising population of subjects -- dead people.

Researchers say they can test new drugs, medical devices and surgical procedures on people who have just died.

Life-support equipment can keep a cadaver's heart and other organs functioning until a research procedure is completed. Unlike clinical trials on living patients, there's no danger of harming a person with a risky experimental treatment.

For example, researchers could induce an irregular heartbeat in a brain-dead patient and see whether an experimental drug helped restore a normal beat. They also could test new ways to do joint replacement surgery or place breathing tubes.

"There are enormous potential benefits," said Mark Wicclair of the University of Pittsburgh's Center for Bioethics and Health Law and West Virginia University philosophy department. "We're probably at a point where it's going to be done more frequently."

But research on the recently dead creates ethical concerns, such as making sure families freely give their consent and avoiding doing anything ghoulish.

"Even though people are dead, we still have ethical principles we apply to them in terms of respectful treatment," Wicclair said.

Wanted to donate organs

Research on brain-dead patients has been going on for at least 25 years, often with little oversight. Now, in response to the growing interest, an expert panel has proposed a set of voluntary guidelines. The guidelines, written by 15 researchers, ethicists, doctors and patient and religious advocates, were published recently in the journal Nature Medicine.

"Respect for persons, a pivotal principle in research ethics, should be extended to the recently dead," the guidelines state.

Two legal definitions of death apply in all 50 states: The traditional definition, in which the heart has irreversibly stopped beating; and brain death, in which brain activity has ceased. A person with no brain activity is legally dead even if life support equipment can keep the heart and lungs working. (A person in a persistent vegetative state, such as the late Terri Schiavo, has brain damage but is not brain dead).

Here is a sampling of studies under way that illustrate how the recently dead are being used in research:

*Testing an artificial lung. Patients who are unable to breathe on their own are put on mechanical ventilators. But the machines can cause pneumonia and other complications, which can be fatal. Dr Brack Hattler of the University of Pittsburgh is developing an artificial lung device that might reduce such complications. Unlike ventilators, the device would enable patients to talk and eat.

The device is inserted into a big vein in the chest. A console outside the body delivers oxygen to the device, where it diffuses into the blood. The device also removes carbon dioxide. It had been tested on animals but was still too risky to try on living people.

Hattler received permission from families to test the device on four brain-dead traffic accident victims. The artificial lung was tested on them for as long as six hours.

"We learned quite a bit," Hattler said.

The families all had wanted to donate their loved ones' organs, but the organs weren't of a high enough quality. The study "was a different way of donating," Hattler said. "It was a way of maximizing the good that could come out of a sad situation."

*Rapid autopsies. Researchers around the country are performing rapid autopsies on patients who gave their consent before dying. Autopsies conducted a few hours after death are proliferating because fresh tissue can yield insights into such diseases as multiple sclerosis, cancer and Alzheimer's.

At Johns Hopkins University, for example, Dr. G. Steven Bova is doing molecular-level studies on prostate cancer that has spread to other parts of the body. In such cases, patients typically die at home.

‘People want to help’

Bova enrolled 32 patients who lived within two hours of Hopkins. Families agreed to transfer the body to the hospital as quickly as possible after the patients died. Autopsies began, on average, just five hours after death.

About one-third of the men Bova approached gave their consent. "People want to help," Bova said. "They don't want their kids to go through the same thing."

*Improving organ transplants. It typically takes 12 to 16 hours from the time an organ donor is declared brain dead to the time organs are removed. During that period, the body is kept on life support to keep organs fresh. Nevertheless, cells release chemicals called cytokines that degrade kidneys and other donatable organs.

Researchers at the University of Texas at Houston and University of Pittsburgh are testing a machine, similar to dialysis, that removes cytokines from the blood. So far, researchers have tested the system for four hours on eight brain-dead subjects. If the system works, it might increase the supply of usable organs available for donation, said University of Pittsburgh researcher Dr. Ramesh Venkataraman.

Studies such as these appear to meet ethical guidelines. They respect the dead and don't raise what ethicists call the "yuck factor."

But bodies don't always receive the respect they deserve. In New York, authorities recently said hundreds of bodies may have been cut up in funeral homes, and body parts such as skin and tendons sold without families' permission.

Ethicists also point to a 2004 New York Times investigation that found that research cadavers had been "mangled in automobile crash tests, blown to bits by land mines or cut up with power saws to be shipped in pieces around the country or even abroad."

However, there's no clear dividing line between acceptable and yucky. Hospitals therefore should appoint committees with diverse memberships "to figure out where the yuck line is," said Dr. Michael DeVita, a critical care specialist at the University of Pittsburgh who chairs the university's committee that oversees research on the dead.

Virus study uses subject on life support

The federal government closely regulates research on living people. And now there are voluntary guidelines for research on the recently dead. 

Herschel Minatra fell into a third category when his family enrolled him in a study at the University of Texas' M.D. Anderson Cancer Center.

Minatra was alive but unconscious, and so sick with complications of cancer that his family was about to take him off life support.

M.D. Anderson researcher Dr. Wadih Arap said that in research projects, the soon-to-be-dead can ethically be treated the same way as the recently dead. But some ethicists disagree, arguing there should be a separate set of guidelines for research subjects that are about to be taken off life support.

Arap used Minatra in a study on targeting drugs to specific sites in the body. Arap injected genetically modified viruses that had identification tags and moved through the body like drugs. Researchers performed biopsies to determine what organs the viruses went to. Researchers tried their best to minimize the visibility of the incisions.

Arap said targeting drugs to only those organs where they're needed could reduce side effects. For example, chemotherapy drugs would go only to tumors, diabetes drugs to the pancreas and Alzheimer's disease drugs to the brain.

Minatra was an old cattleman who had battled lung, colon and skin cancer on and off for more than 30 years. He was grateful to M.D. Anderson doctors for keeping him alive for so long, and "would have been very happy to help the hospital in some way before he died," said his granddaughter, Wendy Morgan.

Minatra had been in the hospital for surgery for a recurrence of his lung cancer. The operation was successful, but complications set in, and after a second surgery, Minatra was put on life support. Doctors said he would never recover enough to care for his wife, who was nearly blind and could not walk. So the family decided to remove life support.

The family enrolled Minatra in the study after receiving assurances he would feel no pain.

"I believe very strongly that programs like this are vital to advancing medicine," Morgan said. "When circumstances present themselves for a dying person to help future generations, they should take that chance."

Guidelines suggest limiting projects to one day

Ethicists agree that strict limits should be placed on the use of dead people as research subjects.

They worry, for example, about possible "biomort emporiums," where cadavers would be kept on life-support equipment for days or weeks.

"We all thought that would be pretty horrifying," said Emory University ethicist Rebecca Pentz, who chaired a 15-member expert panel that recently proposed voluntary guidelines on research with the recently dead.

The guidelines recommend that studies be limited to one day, unless there are "valid scientific reasons" for longer time periods.

Other proposals

"The prospect of prolonged storage of ventilated and profused bodies for research is deemed abhorrent to many and risks undermining public support for research with the recently deceased," the guidelines state.

These are among the other proposed guidelines:

*The body "should be kept covered to the extent possible and [research] procedures should be as minimally invasive as possible." Any disfigurement should be explained ahead of time to the family.

*Research should be approved and overseen by a review board. One-fourth of the board should consist of lay members, "including representatives from ethnic, minority and religious groups."

*Organ transplants have a higher priority. Therefore, research generally should not be done on potential organ donors if the research would damage donatable organs.

*To avoid conflicts of interest, research doctors should not be involved in decisions about withdrawing life support from a patient who might be eligible for research.

*Payments or other incentives to participate in research should not be offered.

*Researchers should try to obtain consent from the patient before the patient dies. If that's not possible, the next of kin should provide consent. If the deceased patient had previously agreed to the research, but the family still objects, the family's wishes generally should be honored.

*Research should have the potential to answer important questions. Otherwise, it "disrespects subjects and wastes resources."

Jim Ritter
 jritter@suntimes.com