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CHAPTER 031

The fact-finding hearing of the Bioethics Review Panel at the National Institutes of Health in Bethesda was carefully structured to feel collegial and unintimidating. Everyone sat at the same long table in the third-floor conference room of the main building, a familiar setting, with notices for upcoming seminars tacked on the walls and the aging coffeemaker sputtering in the corner. The coffee was notoriously awful; nobody drank it.

The six scientists on the review panel dressed a little more formally for this meeting. Most had put on jackets; one even wore a tie. But they sat slouched and relaxed as they talked to the person being investigated, Dr. Ronald Marsh, forty-one, who sat at the same table with them.

“And how, exactly, did this twelve-year-old girl die?”

Dr. Marsh was a professor of medicine at the University of Texas in Austin. “She suffered from congenital transport factor deficiency.” CTFD was a fatal genetic deficiency. “This girl was treated with diet and renal dialysis from the age of nine months. She showed some stunting of growth but no mental retardation. She and her family both wanted this procedure, in the hope that she could have a normal life. Not be tied to a machine forever. As you know, it’s not much of a life, especially for a young kid.”

Those around the table listened impassively.

“And looking to the future,” Marsh continued, “we all recognized that she could not be maintained through adolescence. Hormonal changes were already affecting her metabolism. She was certain to die in the next three to four years. It was on that basis that we undertook the procedure to insert the gene into her body.” He paused. “The risks were known.”

One of the scientists said, “These risks were discussed with the family?”

“Of course. In detail.”

“And with the patient?”

“Yes. She was a bright girl. She was the one who first proposed the procedure. She read about it on the Internet. She understood that the risks were enormous.”

“Did you give the family an estimate of those risks?”

“We did. We told them the chances of success were on the order of three percent.”

“And they went ahead anyway?”

“Yes. The daughter pushed them. She felt that if she was going to die anyway, she might as well take the chance.”

“She was a minor…”

“Yes,” Marsh said. “But she was also the one with the disease.”

“You got signed releases?”

“Yes.”

“We’ve read those releases. Some of us felt the releases struck an unrealistic positive tone, minimizing risks.”

“The releases were prepared by the hospital’s legal department,” Marsh said. “And you will notice the family signed off on a statement that they had been fully informed of the risks. What they were told is also noted in the patient’s charts. We would not have proceeded without fully informed consent.”

During that speech, the head of the panel, Dr. Robert Bellarmino, slipped into the room and eased into a seat at the end of the table.

“So you did the procedure?” Dr. Marsh was asked.

“We did.”

“What vector was used?”

“Modified adenovirus infusion, in combination with standard Barlow immunosuppression protocols.”

“And the outcome?”

“She spiked a fever almost at once. It ran to 107 degrees. She had signs of multiple organ system failure on the second day. Liver and kidney function did not recover. She died on the third day.”

There was a short silence.

“If I may make a personal comment,” Marsh said, “this has been a shattering experience for all of us at the hospital, and shattering for me personally. We had cared for this girl since infancy. She was…beloved by everyone on the staff. She was a little ray of sunshine, whenever she came into the clinic. We attempted this risky procedure because she wanted it. But at night I ask myself, was it the right thing to do? And I always feel I had an obligation to take that risk with the patient, if that was what she wanted. She wanted life. How could I deny her that chance?”

A cough. “But, uh, your team had no experience with gene transplantation.”

“No. We considered sending her to another team.”

“Why didn’t you?”

“No one else would do the procedure.”

“What did that tell you?”

Marsh sighed. “Have any of you seen a patient die of CTFD? Their kidneys necrose. Their livers shut down. Their bodies swell, turn a purple-gray color. They can’t breathe. They’re in agony. They take days to die. Should I have waited for that to happen to this lovely girl? I didn’t think so.”

There was another moment of silence at the table. The mood was distinctly disapproving. “Why is the family suing now?”

Marsh shook his head. “I haven’t been able to speak to them.”

“They have stated in court documents that they weren’t informed.”

“They were,” Marsh said. “Look: we all hoped it would work. Everybody was optimistic. And parents can’t really accept the truth-that a three percent success rate means ninety-seven percent of the patients die. Ninety-seven percent. It’s almost certain death. They knew that, and when their hopes were dashed, they felt cheated. But we never misled them.”

After Dr. Marshleft the room, the panel met in closed session. Of the seven members on the panel, six were outraged. They argued that Marsh was not telling the truth now, and had not told the truth before. They said he was reckless. They said that he gave genetics a bad name, which the field now had to overcome. They spoke of the Wild West, of his going off half-cocked.

They were clearly moving toward censure of Marsh, and recommending that he lose his license and his ability to apply for government grants.

The head of the panel, Rob Bellarmino, said nothing for a long time. Finally, he cleared his throat. “I can’t help but reflect,” he said, “that these arguments were exactly the same as those first voiced when Christiaan Barnard did the first heart transplant.”

“But this isn’t the first of anything-”

“Going off half-cocked. Not seeking proper authorization. Liable to lawsuits. Let me remind you,” Bellarmino said, “what Barnard’s original statistics were. His first seventeen patients died almost immediately. He was called a killer and a charlatan. But now, more than two thousand heart transplants are performed every year in this country. Most live five to fifteen years. Kidney transplants are routine. Lung and liver transplants that were considered outrageous a few years ago are accepted now. Every new therapy passes through a hazardous, pioneering stage. And we will always rely on courageous individuals, such as Dr. Marsh, to take risks.”

“But so many rules were broken-”

“What would you do to Dr. Marsh?” Bellarmino said. “The man can’t sleep at night. You see it in his face. His beloved patient died under his care. What greater punishment will you inflict? And who are you to tell him he did the wrong thing?”

“The ethics rules-”

“None of us looked in that little girl’s eyes. None of us knew her life, her pain, her hopes. Marsh did. He knew her for years. Will we now stand in judgment of him?”

The room was quiet.

In the end, they voted to censure the University of Texas legal staff, with no penalty for Dr. Marsh. Bellarmino had turned them around, one of the panel said later. “It was classic Rob Bellarmino. Talking like a preacher, subtly invoking God, and somehow getting everyone to push the envelope, no matter who got hurt, no matter what happened. Rob can justify anything. He’s brilliant at it.”

But in fact, before the final vote was taken, Bellarmino had left the room, because he was late for his next meeting.

From the bioethicspanel meeting, Bellarmino returned to his lab, where he was meeting with one of his postdocs. The kid had come to him from Cornell Medical Center, where he had done remarkable work on the mechanisms that controlled chromatin formation.

Normally, the DNA of a cell was found inside the nucleus. Most people imagined DNA in the form of a double helix, the famous twisting staircase discovered by Watson and Crick. But that staircase was only one of three forms that DNA might take within the cell. DNA could also form a single strand, or a more condensed structure called a centromere. The particular form was dependent on the proteins associated with the DNA.

This was important because when DNA was compressed, its genes were unavailable to the cell. One way to control genes was to change the chromatin of various sections of DNA.

So, for example, when genes were injected into new cells, steps also had to be taken to keep the chromatin in an available form, through the use of added chemicals.

Bellarmino’s new postdoc had done breakthrough research on methylation by certain proteins, and their effect on chromatin structure. The kid’s paper, “Genome-Protein Accessibility Control and Adenine Methyltransferase,” was a model of clear writing. It was bound to be important, and would make the kid’s reputation.

Bellarmino was sitting in his office with the kid, who was looking eager as Bellarmino scanned the paper. “Excellent, just excellent.” He tapped the paper. “I think this work does great credit to the lab. And of course to you.”

“Thank you, Rob,” the kid said.

“And you have the seven co-authors in place, and I am appropriately high on the list,” Bellarmino said.

“Third,” the kid said, “but if you felt second position was warranted-”

“Actually, I am remembering a conversation we had a few months back, in which we discussed possible methylation mechanisms, and I suggested to you-”

“Yes, I remember…”

“The very mechanisms you elucidate here. I feel rather strongly that I should be the lead author.”

The kid blinked. “Umm…” He swallowed.

“That ensures the paper will be cited more often,” Bellarmino said, “which is important for a contribution of this magnitude. And of course the exact listing is just a formality. As second author you will be understood to have done the footwork here, the fill-in-the-gaps labor. From your standpoint, it’s really a win-win. You will get greater citations, and you will see much larger grants coming your way.” He smiled. “I can assure you of that. Your next work will be entirely independent. And in a year or two, I’ll be supporting you for a lab of your own.”

“I, uh…” The kid gulped. “I understand.”

“Good, good. Make these changes, shoot it back to me, and I’ll submit it to Nature. I think this deserves a better platform than Science, which is a little down at the heels these days. I’ll call over to Nature and make sure the editor understands the importance of this paper, and see that we get immediate publication.”

“Thanks, Rob,” the kid said.

“Anytime,” Rob Bellarmino said.

“wet art” on display

Transgenic Organisms in Galleries

Living Creatures for Sale in London, South African artist Laura Cinti displayed a transgenic cactus that contained human genetic material, and grew human hairs. Cinti said, “The cactus with all its hairs coming out is showing all the desires, all the signs of sexuality. It doesn’t want to be trapped. It wants to be released.”

When asked about the public reaction to the cactus, Cinti said, “Bald men are particularly interested.”

Artist Marta de Menezes created modified butterflies where one wing was different from the other. She said, “People were very shocked at first. They didn’t think it was a good idea.” She said that, next, she would make the stripes of zebra fish vertical instead of horizontal so the fish would look more like zebras. These changes would be inherited.

Finnish artist Oron Catts grew pig wings in culture from pig bone marrow stem cells. He said the artist’s team played music to the pig cells to make them grow. “We downloaded lots of pig songs…and played them to the cells.” He said the cells seemed to do better with music.

Chicago-based artist Eduardo Kac created a transgenic rabbit called Alba that glowed green. The fertilized egg of an albino rabbit was injected with GPF, the gene for green fluorescent protein from a Pacific Northwest jellyfish. The animal that grew from the egg now glows. A furor resulted. Kac observed that “[the rabbit] does make some people uncomfortable,” but noted that GPF is a common research tool and has been injected into yeast, molds, plants, fruit flies, mice, and cow embryos. Kac said he was looking forward to making a fluorescent dog.

Alba died prematurely of unknown causes. So did the transgenic cactuses.

In 2003 the first transgenic pet was offered for sale to the public. A red-fluorescing zebra fish, it was created by Dr. Zhiyuan Gong in Singapore, and licensed to a company in Austin, Texas. It was marketed under the name GloFish, after two years of review by federal and state agencies, which concluded the fish were safe, so long as they were not eaten.