For more than a decade, Dr. Brack Hattler has labored on a tiny device with big potential - an artificial lung to breathe for people when their organs fail.
The lung showed promise in cows. But Hattler was nervous about the risky next step - testing it in people. "We didn't want to be making corrections in a live patient," said the University of Pittsburgh transplant surgeon.
So he turned to a group that scientists have mostly shied away from: the living dead.
Hattler is one of a small but growing number of researchers conducting studies in people just declared brain-dead or who are "nearly dead" - terminally ill patients being kept alive only by machines.
Since Hattler's request, the university has formed a special review board to handle such research proposals. The Committee for Oversight of Research Involving the Dead, created last fall, has already approved eight requests.
The University of Chicago and the M.D. Anderson Cancer Center in Houston also have studies in progress that involve the living dead. The research ranges from testing experimental medical devices to tracing the path of drugs through the body.
"From a pure science point of view, this is just too good a research population to ignore," said Dr. Michael DeVita, an internist and member of the Ethics Committee at the University of Pittsburgh Medical Center.
Proponents of the research argue that it allows scientists to explore questions that are impossible to answer with animals and cadavers, the usual subjects in risky research. As long as researchers obtain proper consent and are respectful, many ethicists concur, working on the living dead isn't much different from using someone as an organ donor.
"While it may seem macabre or in some ways bizarre, it's still better to reduce the risk living humans face," says Arthur Caplan, an ethicist at the University of Pennsylvania. "We're not talking about row after row of brain-dead people like in the movie Coma."
But not everyone is comfortable with the practice. Jacqueline Glover, associate director of the Center for Health Ethics and Law at West Virginia University, worries about the potential for abuse.
'Who will be next?'
"The research is undeniably valuable, but where will we stop?" she said last year in the Hastings Center Report, a leading bioethics journal.
"If we start with the already dead patient and move to the nearly dead patient, who will be next?"
M.D. Anderson's decision to work not just with the brain-dead but also with the dying - "terminal-wean" patients who will die once life support is withdrawn - has provoked criticism.
"Terminal-wean patients are not dead," says DeVita, the Pittsburgh ethics board member. "They can feel pain. They can feel anxiety. They can be aware."
As a result, he says, Pittsburgh has declined to permit such research.
Wadih Arap, an oncologist at M.D. Anderson who is conducting studies on brain-dead and nearly dead patients, acknowledges those concerns. He worries, for example, that a subject might die during an experiment when relatives are not present.
"This is one of our darkest fears," he says. "We're very concerned about a family not being able to say its proper goodbyes."
Still, he says, the scientific lessons are worth the risk.
Decades of discussion
The idea of experimenting on the brain-dead is not new. In a provocative 1974 essay in Harper's Magazine, Dr. Willard Gaylin discussed the potential use of such "neomorts," as he called the newly dead. Bodies would be artificially maintained in cavernous "bioemporiums" for research or as a source of organs. It's a concept that author Robin Cook later wove into the plot of his novel Coma.
In the 1980s, doctors published two studies using brain-dead subjects, drawing intense criticism. "The yuck factor plays a big role here," says Caplan, who suspects that since then most institutions haven't wanted to deal with the thorny ethical issues.
A few years ago, executives at AbioMed, a Massachusetts company developing an artificial human heart, decided against testing its device in brain-dead subjects. "I think it's fair to say that it was someplace they didn't want to go," said Edward Berger, the company's vice president for strategic planning and policy.
Researchers at other medical institutions, including those at the Johns Hopkins University and the University of Maryland, say they are not planning studies either. But Dr. Michael Klag, who oversees clinical research at Hopkins, said he plans to watch the current experiments closely.
No national guidelines or laws exist for research on the brain-dead. So officials at M.D. Anderson and Pittsburgh say they have spent considerable time developing their own.
Under these guidelines, researchers can experiment on live subjects only if their organs are found unsuitable for transplant, typically because of cancer or an infection such as HIV. Researchers also cannot be involved in the decision to declare death or in recruiting families for their experiments.
"The dying process is considered sacrosanct," says Rebecca Pentz, an Emory University ethicist who helped develop M.D. Anderson's policies. "We wanted to make sure we weren't harming patients or families at a time when they were vulnerable."
'Knowing it's a gift'
At Pittsburgh, Hattler's first subject was a woman in her 40s who had been in a car accident. After doctors declared her brain-dead, an organ donor team arrived but found she had a hepatitis infection that made her organs unsuitable.
So the donor team asked the woman's family if Hattler could include her in a test of his artificial lung, which is designed to replace bulky ventilators. They agreed.
About 1 a.m., as the family watched, Hattler and his team - in an excess of caution - gave the woman a local anesthetic to numb her skin. Then they began threading the catheter-like device through a leg vein until it neared her heart. The device pumped oxygen into the woman's blood and filtered carbon dioxide out.
Five hours later, after drawing several blood samples and completing tests, Hattler quietly packed up and left. Doctors switched off the machines, and 15 minutes later the woman's heart stopped.
"You approach this knowing it's a gift," Hattler says. "So you treat it with respect."
Most researchers say they make every effort to be considerate and collect data as quickly as possible so they don't interfere with grieving families. "Everybody wants to get it over with," says Arap, the M.D. Anderson oncologist. "We are very sensitive to that."
Before beginning each of his three studies, Arap choreographed his team's movements to the tiniest detail, making sketches and practice runs until they could collect data in less than an hour.
In an effort to create more effective cancer drugs, Arap is trying to understand how cells navigate the body's complex network of blood vessels to arrive in specific destinations. After years working in mice, he has determined that cells rely on a sort of biological ZIP code system to reach their destination.
But to see if the same held true in humans, he would need to snip out numerous organ tissue samples - a procedure that would have been unethical in a healthy volunteer.
His first experiment was on a man with cancer. Forty minutes after his team rushed into the brain-dead man's hospital room, they had finished injecting their chemicals and collecting tissue. "One of the nurses commented it looked like an episode of ER," Arap says.
He says his studies have turned up a promising new drug target for prostate cancer. He has published some of his results in the journal Nature Medicine.
Pittsburgh's Hattler, meanwhile, has found that his artificial lung seems to perform just as well in people as it does in cows. His experiments also have showed him that he needed to make the device a little smaller. Next year he is planning to test it in human subjects in Europe.
"There's as much benefit to this as donating an organ. When you donate an organ, you benefit one person," Hattler says. "If you are part of bringing forward a whole new technology, you can benefit thousands."