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Chapter 31-32

CHapter 031
The fact-findinghearing 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 toNature. I think this deserves a better platform thanScience, which is a little down at the heels these days. I'll call over toNature 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.
CHapter 032
Madame Bond,"the first-grade teacher said, "your son is a delightful boy, but he is having trouble with his math. Addition comes slowly to him; subtraction is even more difficult. However, his French is much improved."
"I am glad to know that," Gail Bond said. "The move here from London was hard for him. But I must admit, I'm surprised about his difficulty with math."
"Because you are a scientist, you mean?"
"I suppose so, yes. I work at the Institut National here in Paris," she said, "and Evan's father is an investment banker; he works all day with numbers."
"Well," the teacher replied, "as you are a geneticist, I am sure you know everything is not in the genes. Sometimes the child of a great artist cannot draw. But I must tell you that it does your son no good if you do his homework for him."
"Sorry?" Gail Bond said. "Do his homework?"
"Well, this must be the case," the teacher said. "You or someone else in the household."
"I don't understand."
"Evan's homework is always perfect. But when there is a quiz in class, he does poorly. Evidently, someone is doing his homework for him."
Gail Bond shook her head. "But I don't know who it could be," she said. "My son comes home from school and only the housekeeper is there when he does his homework. She doesn't speak much French. I return at five, and by then his homework is finished. Or so he tells me."
"You do not review it?"
"No. Never. He says there is no need."
"Well," the teacher said, "he is getting help from somewhere." She took out the homework sheets and spread them on the desk. "You see? Every problem, on every sheet. Perfect."
"I see," Gail said, staring at the papers. "And these stains..." There were small green and white stains on the paper, droplets.
"Often these marks are present. Usually at the bottom of the sheet. As if something were spilled."
"I think I know who is helping him," Gail Bond said.
"Who?"
"It's someone from the lab."
She unlocked thedoor to the apartment and heard Gerard call, "Hello, sweetheart," exactly as her husband did.
"Hi, Gerard," she said. "What's new with you?"
"I need a bath."
"I'll see that you get one," she said. She walked into the hallway where Gerard was standing on his perch. He was a transgenic African grey parrot, now two years old. While he was a chick, he had received a variety of human genes, so far with no noticeable effect.
"You look good, baby, I've missed you," Gerard said, again imitating her husband's voice.
"Thank you," she said. "I have a question for you, Gerard."
"Okay, if you insist."
"Tell me. What is the answer to thirteen minus seven?"
"I don't know."
She hesitated. "What is the answer to thirteen take away seven?" That was how Evan would phrase it.
Promptly, the bird said, "Six."
"Eleven take away four?"
"Seven."
"Twelve take away two?"
"Ten."
She frowned. "Twenty-four take away eleven?"
"Oh. Oh. Oh," the parrot said, moving on the perch. "You try to trick me. Thirteen."
"What's one-oh-one take away seventy?"
"Thirty-one. But we never get so many numbers. Most is two numbers."
"We?"
Gerard said nothing. He ducked his head rhythmically. He began to sing, "I love a parade..."
"Gerard," Gail said, "does Evan ask you for help?"
"Oh sure." And then a perfect imitation of Evan: "Hey, Gerrie, come and help me. It's too hard for me." Then a whine: "It's toohaaard... "
Gail said, "I have to get the video camera."
"Am I a star? Am I a star?"
"Yes," she said, "you are a star."
He spoke in an American drawl: "We're sorry we're late but we had to pick up our son Hank."
"What movie is that?" she said.
The same drawl: "Now Jo, just take it easy."
"You're not going to tell me, are you?" she said.
"I need a bath," Gerard said, "before any filming. You promised me a bath."
Gail Bond hurried off to get the camera.
During his first yearof life, Gerard showed little effect from the human transgenes that had been injected into him as a chick by Yoshi Tomizu and Gail Bond in the laboratory of Maurice Grolier at the Institut National in Paris. This was not surprising. The successful injection of transgenes was a tricky business, and required dozens, even hundreds, of attempts before it worked properly. That was because multiple conditions had to be fulfilled for the gene to work in a new environment.
First, the gene had to be incorporated correctly into the existing genetic material of the animal. Sometimes the new gene was incorporated backward, which had a negative effect, or none at all. Sometimes it was inserted into an unstable region of the genome, and triggered lethal cancer in the animal. That was rather common.
Furthermore, transgenics was never a matter of inserting a single gene. Researchers also had to insert the associated genes necessary for the primary gene to function. For example, most genes had insulators and promoters. The promoters might make proteins that switched off the animal's own genes, to allow the new addition to take over. Or they might enhance the workings of the injected gene itself. The insulators kept the new gene separated from the genes around it. They also made sure the new genetic material remained available within the cell.
Complex as they were, these considerations didn't take into account the further intricacies that might arise from messenger RNAs within the cell. Or from the genes that controlled translation. And so on.
In reality, the task of injecting a gene into an animal and making it work more closely resembled debugging a computer program than it did any biological process. You had to keep fixing the errors, making adjustments, eliminating unwanted effects, until you got the thing working. And then you had to wait for downstream effects to show up, sometimes years later.
That was why the lab felt that Gail Bond should take Gerard home, and keep him as a pet for a while. To see if any positive or untoward effects showed up. Home rearing was especially important because African greys were highly intelligent - generally considered as intelligent as chimpanzees - and with a far greater capacity for language. Using sign language or computer keyboards, a few nonhuman primates had mastered about 150 words. But that was merely average for a grey parrot. Some grey parrots had as many as a thousand words. So they needed the kind of interaction and stimulation found in a human environment. They couldn't be left in an animal holding facility, around mice and hamsters, or they would go mad from lack of stimulation.
Indeed, animal activists believed that many grey parrot pets were mentally disturbed as a result of insufficient interaction. It was as if they had been held in solitary confinement, year after year. A grey parrot required at least as much interaction as a human being. More, some scientists argued.
Gerard was finger-trained as a chick, and began talking early. He already had quite a vocabulary when Gail, who was thirty-one and married to an investment banker, brought him home to her apartment. As Gerard came into the living room, he said, "Hey, nice place, Gail. Way to go." (He had unfortunately picked up bits of American slang from watching television at the lab.)
"I'm glad you like it, Gerard," she said.
"I was just saying that," the parrot said.
"You mean you don't like it?"
"I mean I was just saying that."
"Okay."
"Just an observation."
"Right. Fine."
She immediately made notations in a logbook. Gerard's speech might prove highly significant. One of the goals of the transgenic experiment was to see to what extent scientists could modify the intelligent behavior of non-human animals. Primates were off-limits - too many rules and regulations - but people weren't so sensitive about parrots. There were no ethics committees to supervise parrot experimentation. So the Grolier lab worked with African greys.
Among the things they were looking for was evidence of self-awareness in the parrot's speech. Parrots were known to be self-aware. They recognized themselves in mirrors. But speech was different. Parrots did not reliably use the wordI when referring to themselves. Generally, when they used the personal pronoun it was to quote someone else.
The question was whether a transgenic parrot would ever use the wordI unambiguously. And it seemed to Gail Bond that Gerard had just done exactly that.
It was a good start.
Her husband,Richard, showed little interest in the new arrival. His sole reaction was to shrug and say, "Don't look for me to clean that cage." Gail said she would not. Her son was more enthusiastic. Evan immediately began to play with Gerard, putting him on his finger, and later on his shoulder. As the weeks went on, it was Evan who spent time with the bird, who bonded with it, who kept it on his shoulder much of the time.
And, it seemed, who got help from the bird.
Gail set upthe video camera on a tripod, adjusted the frame, and turned the camera on. Some grey parrots were able to count, and there were claims that some had a rudimentary understanding of the concept of zero. But none was able to do arithmetic.
Except Gerard.
She had to work very hard to conceal her excitement. "Gerard," she said, in her calmest voice, "I am going to show you a picture and I want you to tell me what it says." She showed him one sheet from her son's homework, folding it to reveal a single problem. She covered the answer with her thumb.
"I did that already."
"But what does this say?" Gail asked, pointing to the problem. It was fifteen minus seven.
"You have to say it."
"Can you look at this paper and tell me the answer?" she said.
"You have to say it," Gerard repeated. He was hopping from one leg to the other on his perch, getting irritable. He kept glancing at the camera. Gerard didn't like to be embarrassed.
Gail said, "It says fifteen take away seven."
"Eight," the parrot replied, at once.
Gail resistedthe temptation to turn to the camera and shriek with delight. Instead, she calmly turned the page to reveal another problem. "Now. What is twenty-three take away nine?"
"Fourteen."
"Very good. And now..."
"You promised me," Gerard said.
"I promised you?"
"Yes, you promised me," he said. "You know..."
He meant the bath.
"I'll do that later," she said. "For now..."
"You promised me." Sulky tone. "My bath."
"Gerard, I am going to show you this next problem. And ask you: What is twenty-nine take away eight?"
"I hope they are watching," he said, in an odd voice. "They'll see. They'll see and they'll know and they'll say, 'Why, she wouldn't even harm a fly.'"
"Gerard. Now, please pay attention. What is twenty-nine take away eight?"
Gerard opened his mouth. The front doorbell rang. Gail was close enough to the bird to know that Gerard himself had made the sound. He could imitate all sorts of sounds perfectly - doorbells, phone rings, toilet flushes.
"Gerard, please..."
The sound of footsteps. A click, and a creak as the front door opened.
"You look good, baby, I've missed you," Gerard said, imitating her husband's voice.
"Gerard," she began.
A woman's voice: "Oh Richard, it's been so long..."
Silence. Sound of kissing.
Gail froze, watching Gerard. The parrot continued, his beak hardly moving. He was like a tape recorder.
The woman's voice: "Are we alone?"
"Yes," her husband said. "Kid doesn't come back until three."
"And what about, uh..."
"Gail is at a conference in Geneva."
"Oh, so we have all day. Oh, God..."
More kissing.
Two pairs of footsteps. Crossing the room.
Her husband: "You want something to drink?"
"Maybe later, baby. Right now, all I want isyou. "
Gail turned, and switched the video off.
Gerard said, "Now will you give me my bath?"
She glared at him.
The bedroom door slammed shut.
Creaking of the bedsprings. A woman squealing, laughing. More creaking springs.
"Stop it, Gerard," Gail said.
"I knew you would want to know," he said.
"I hate thatfucking bird," her husband said, later that night. They were in the bedroom.
"That's not the point," she said. "You'll do what you want, Richard. But not in my house. Not in our bed." She had already changed the sheets, but even so, she didn't want to sit on the bed. Or go near it. She was standing on the other side of the room, by the window. Paris traffic outside.
"It was just that one time," he said.
She hated it when he lied to her. "When I was in Geneva," she said. "Do you want me to ask Gerard if there were other times?"
"No. Leave the bird out of it."
"There were other times," she said.
"What do you want me to say, Gail. I'm sorry, all right? I'm sorry."
"I don't want you to say anything," she said. "I want you not to do it again. I want you to keep your fucking women out of this house."
"Right. Fine. I will do that. Can we drop it now?"
"Yes," she said. "We can drop it now."
"I hate that fucking bird."
She walked out of the room. "If you touch him," she said, "I'll kill you."
"Where are you going?"
"Out."
She metYoshi Tomizu at his apartment. They had begun their affair a year before and had resumed it again in Geneva. Yoshi had a wife and child in Tokyo, and he would be returning there in the fall. So it was just a friendship with privileges.
"You feel tense," he said, stroking her back. He had wonderful hands. "Did you argue with Richard?"
"Not really. A bit." She looked at the moonlight coming in through the window, surprisingly bright.
"Then what is it?" Yoshi asked.
"I'm worried about Gerard."
"Why?"
"Richard hates him. Really hates him."
"Oh, he wouldn't do anything. It's such a valuable animal."
"He might," she said. She sat up in bed. "Maybe I should go back."
Yoshi shrugged. "If you think..."
"I'm sorry," she said.
He kissed her lightly. "Do what you think is best."
Gail sighed. "You're right," she said. "I'm being silly." She slid back down under the covers. "Tell me I am being silly. Please."