Doctor Who Broke Restriction on Fetal Tests Under Attack

Twelve days ago Curt Freed, a neurobiologist at the University of Colorado Health Sciences Center in Denver, led a team that implanted brain cells from an aborted fetus into the brain of a 52-year-old victim of Parkinson’s disease in hopes of improving the man’s condition. It was the first time this operation was performed in the United States.

But despite their ardor for the technique itself, most of Freed’s colleagues, gathered here this week for the annual meeting of the Society For Neuroscience, are not pleased with him.

It is not that Freed was the first to attempt the operation: It has already been performed an estimated 35 times in other countries, most notably Mexico, Cuba and Spain. It is not even jealousy that he was the first in the United States, although hints of the green monster of envy are visible in the statements of others poised to do the procedure.

The problem is when he did it.

In May, the National Institutes of Health imposed a moratorium on all federally sponsored research involving fetal tissues and convened a panel to consider the ethical issues involved with using a material whose ultimate source is voluntary abortions. That panel, chaired by retired U.S. District Judge Arlin Adams of Philadelphia, is scheduled to present its report to the NIH in mid-December.

Bad Timing

“Curt’s timing couldn’t possibly have been worse,” said neurobiologist Roy A. E. Bakay of Emory University in Atlanta, echoing a sentiment that is apparently widely felt.

Although Freed conducted the transplant with private funds, the operation “was a real slap in the face to the panel,” said neurobiologist Don Marshall Gash of the University of Rochester School of Medicine. “He flouted the moratorium and jeopardized the panel’s chances of coming up with acceptable voluntary guidelines.”

Freed’s action intensified an ongoing debate about the effectiveness of surgery as a therapy for Parkinson’s disease, the government’s role in testing the efficacy of such a procedure and the use of fetal tissues in research. Few of those issues seem likely to be settled soon.

And underlying that debate is the very real fear that the government may enact laws rather than voluntary guidelines covering the use of fetuses or may even ban their use.

‘Obey the Law’

“I think we have to pay attention to the moratorium . . . to assure the public we will adhere to any guidelines and that we, too, obey the law,” said neurobiologist Barry G. Hoffer of the University of Colorado, who is both a member of the Adams panel and an intense rival of Freed.

“In Curt’s defense, I have to say that . . . he had the right under the law to do what he did,” said Murray Goldstein, head of the NIH branch of the National Institute of Neurological and Communicative Diseases and Stroke in Bethesda, Md., which funds fetal transplant research. “But I think it would have been more socially acceptable to await the recommendations of the panel.”

Discussing the imbroglio in his first extended interview since the transplant operation, Freed denied making a political statement in the timing of the operation.

“I am in no way in any battle with any person or committee,” Freed said. “I did this strictly for scientific reasons.” And the political considerations? “I guess what I have done will have to speak for itself,” he said.

Parkinson’s disease is a debilitating ailment that afflicts more than a million Americans, most of them over the age of 50. It causes severe trembling, muscular rigidity and, in some 30% of the cases, impairs thought processes.

Its cause is not known, but the symptoms are produced by the death of brain cells that produce a hormone called dopamine, which helps transmit nerve impulses between brain cells. For more than a decade, researchers have been demonstrating that transplanting dopamine-producing cells into the brain of rodents and primates can eliminate many of the symptoms of Parkinson’s.

Nonetheless, researchers were startled two years ago when neurosurgeon Ignacio Madrazo of La Raza Medical Center in Mexico City announced at the annual meeting of the Society For Neuroscience that he had successfully restored mobility to two Parkinson’s patients by implanting tissues from their own adrenal glands into their brains. The adrenal tissue secretes dopamine that would not normally reach the brain because of the blood-brain barrier, which protects fragile brain tissues from noxious chemicals in the blood.

Use of the technique has spread rapidly and more than 200 Parkinson’s patients worldwide have now received adrenal grafts. But the jury is still out on the technique’s value. Some researchers like Madrazo, who with 50 patients have treated far more people than anyone else, report spectacular results in as many as a third of their patients. Perhaps another third receive a little benefit or remain stable, but the remainder continue to deteriorate.

Other scientists are not optimistic. “The results have not been impressive,” neurologist Anders Bjorklund of the University of Lund in Sweden told the neuroscientists.

One problem is that each neurosurgeon has performed the operation in a slightly different manner and has used different standards to assess their patients before and after the operation, said neurologist Jack B. Penney of the University of Michigan. Combining everyone’s data to determine the technique’s value “will be extremely difficult,” he said.

Fetal Cells More Effective

But whether the adrenal transplant is effective may already be a moot point. One thing on which virtually everyone agrees is that animal studies clearly show that fetal brain cells are much more effective than adrenal tissues in reversing Parkinson’s disease. Because the fetal cells are young and still growing, they survive much better than adult cells after the transplant. They are also less likely than adult tissues to provoke an immune response that would lead to rejection.

Again, Madrazo was in the forefront, reporting in January that he had observed clinical improvement in two Parkinson’s patients given fetal brain cells. But Mexico is a Catholic country where abortion is forbidden, and Madrazo has not been able to obtain tissue for other patients.

Neurosurgeon Hilda Molina of the Hospital Hermanos Ameijeiras in Havana, Cuba, has implanted fetal tissue in 10 patients. Molina was not at the meeting here, but Bjorklund, who has been consulting regularly with her, said that the four patients who have now been observed for at least six months show “clear improvement.”

Fetal tissues have also been implanted eight times in England, six times in Spain and an undetermined number of times in China. At least two U.S. researchers have announced that they planned to do the procedure: neurobiologists Irwin J. Kopin of the National Institute of Neurological and Communicative Diseases and Stroke and D. Eugene Redmond of Yale University.

In fact, it was Kopin’s application to NIH officials for permission to conduct a fetal cell transplant more than a year ago that ultimately triggered the current moratorium. Freed, in contrast, had never announced plans to perform the operation and had even frequently argued that the adrenal transplants were premature--a position that he still holds.

Freed’s procedure, furthermore, “is not new and not innovative,” Kopin said. “It’s hard to see why he did it at this time, unless he had the objective of being spectacular.”

Freed bristles at the suggestion that his procedure is not innovative. “How can Irv (Kopin) know that? We haven’t told anyone the details of the surgery, and we won’t until we write a scientific report after we have monitored the patient for at least six months.”

In fact, Freed has spread the implanted tissue over a much wider area of the brain than other researchers have so that more of the patient’s brain will receive dopamine. “There are a lot of other things that we have done differently. We think we have been very innovative. Other researchers will be pleased when they read our report.”

Time for Human Experiments

Freed also disavows a desire to be spectacular. “The time had simply come for human experiments,” he said.

“We started working with monkeys four years ago with the goal of doing a human transplant, and we’ve progressed steadily toward that goal. We found that the procedure is safe and behaviorally effective in monkeys. We’ve taken monkeys whose hands were completely disabled and restored normal function. Other people have seen the same thing. All the pieces were in place. We were ready to take the next step.”

The timing of the operation had nothing to do with the Adams panel’s deliberations or, as some critics have charged, with the then-impending neurosciences meeting, he said. “We’ve been following this patient’s progress for the last five months to get a baseline so we will know if the operation benefited him. We had a one-month ‘window’ ” in October and November when everyone on the team would be available for the operation, when the operating room would be available and when the abortion clinic would be able to provide tissue.

“I spent one day a week for three weeks sitting in the clinic, drinking coffee all day and looking at tissue that was unacceptable,” Freed said. “If I hadn’t found some useful tissue (on the fourth day), we wouldn’t have had another window until after the first of the year and this uproar would never have happened.”

Freed emphasizes that he followed all the rules as they were written. He said he obtained appropriate permission from the university’s institutional review board, as well as from his dean and the chancellor. He checked in with the NIH frequently to make sure that he was interpreting the moratorium correctly, that it prohibited only a transplant with government funds. He also followed the ethical guidelines that the Adams panel is expected to recommend--most notably that the woman’s decision to have an abortion be completely separated from the decision to use the tissue for therapy.

“I was fortunate that I had $150,000 that was given to me a couple of years ago by a wealthy philanthropist who had Parkinson’s,” he said. “That money is being used to pay all the patient’s hospital bills.”

Time, Freed believes, will provide a measure of vindication. “People may be upset with me now, but in six months, everyone will want to know what happened to my patient.”

Denies Political Motive

Although Freed argued that he had “no political motivation” for the operation, he does admit to some strong opinions about the moratorium.

“I don’t think science can wait, or should have to wait, because of an outstanding political question,” he said. “When the government restricts scientific research, even though it doesn’t prohibit it, that casts a pall over the entire research community.”

Other scientists would prefer to avoid such bold statements. “Curt is not the spokesman we want for this issue,” said Gash, of the University of Rochester School of Medicine. “We feel a delicate balance right now in trying to set up voluntary guidelines. . . . He’s providing fodder for the right-to-life people.”

“This jeopardizes the integrity of the scientific community in its negotiations with people who have a right to disagree with us,” Kopin said. “If we can’t influence our own people to conform to a moratorium, then people will wonder how we can get them to conform to voluntary guidelines.”

Freed, meanwhile, says he is “very comfortable with my position. The minute we finished the operation, I knew we had done the right thing. I’m surprised and disappointed by the intensity of the negative reaction, but I’d do it all over again in a minute.”