His Brother's Keeper

by Jonathan Weiner

  The next morning in the Galaxy auditorium there were spiral notebooks and pens stacked neatly beside the gleaming regular and decaf coffee urns. There were heavy curtains drawn across the port-holes, to allow for showing slides from the PowerPoint projector that Cohen had carried aboard with his luggage. Most of the talks were technical (“Cytogenetic Diagnosis: What do we do now?”) and concerned matters like the latest techniques for the biopsy of embryos, the freezing and thawing of embryos, the implantation of embryos. Lee Silver sat just behind the PowerPoint projector with a new Mac laptop open on his chair arm, speed-typing his notes. “You realize that if any right-to-lifers were here,” he whispered to me, “they would be going absolutely bonkers. What they’re doing is experimenting on living embryos. This is illegal in most countries.” It is also forbidden in the United States if the work is done with government grants from the National Institutes of Health or the National Science Foundation. But because it was funded by Cohen’s private clients at the IVF clinic, it was legal, and it furthered the cause that he returned to again and again: his goal of 100 percent implantation rates.

  To me, the talks began to get interesting when Cohen’s chief scientist turned to the question of longevity. Suppose the telomeres, the very tips of our chromosomes, really do turn out to be the key to long life, as some biologists have suggested. If that happens, should they begin selecting human embryos for the ones with the longest telomeres, selecting for Methuselahs?

  “Aging,” Jacques said musingly from the podium, after his chief scientist’s talk, gesturing with his cup and saucer at a slide on the wall. “Aging is a disease—but not considered as such by ethicists. If you’re a potential parent, would you not be happy to give the best to your child?

  “Do we do this?” he asked. In his clinic they already selected babies based on their odds of living an average life span. Should they begin to select babies based on whether they would live longer than average? “And do we talk about this in public?” This would be the first time their clinic moved from selecting embryos to avoid diseases to selecting embryos to enhance their quality of life—unless the world did agree to call aging a disease. “The question is, how to proceed with this in terms of advertising so we don’t get shut down.”

  “You have to realize how fast people go through enormous opinion changes,” Silver said reassuringly from his seat by the projector.

  “Do we want to do this?” Cohen repeated. “I mean, we all know who will come first,” he said, and gave the group a big, warm, amused, confidential grin. He was thinking of those die-hard clients, the rich and crazy ones, God bless them, who always want the latest.

  That was Sunday. When I found my way to the lecture hall on Monday morning, I saw that Jacques Cohen was on the podium again, listening to a speaker. The lecture in progress sounded technical. I sat down in the back row of seats and tried to follow what was going on.

  Speaker: “Mrs. Smith had genetic abnormalities. I can mention that name because it’s so generic. Her name really was Mrs. Smith….”

  Cohen, a few minutes later: “And she chose to deliver just then, yes?”

  Voice from audience, with satisfaction, as if to convey an arrival after a long haul. A foreign-accented drawl: “Ma-a-a-y-y-y 28.”

  They were talking about something called cytoplasmic transfer by injection.

  I started listening more closely.

  Cohen said he knew of only a few other groups who were succeeding in their cytoplasmic transfers. “The groups in California announced doing it—for PR reasons,” he said. Then, in reply to a question from the audience, he said, “The parents are informed, they get many hours of training, they sign forms of very well-informed consent.”

  I strolled up to the PowerPoint projector and leaned over Lee Silver, who was typing madly on his laptop. “What’s going on?” I whispered.

  Silver whispered back, electrifyingly, “Gene therapy! He’s talking about the first babies born with genetic engineering. They make it work. I don’t know if even they themselves appreciate that!”

  This was the same project that Cohen had mentioned over our dinner at Princeton, when the world was talking about the birth of Dolly. Dolly was created by nuclear transfer. In that procedure, the nucleus is extracted from an egg, and another nucleus is transferred in. But these babies were made by cytoplasmic transfer. In this procedure, cytoplasm is extracted from a fertile egg and transferred into an infertile one. It is something like taking egg white from one egg with a syringe and injecting it into another.

  Most of the DNA in a cell is packed inside the nucleus. But there is some DNA in the cytoplasm, too. The mitochondria, the energy packs that float in the cytoplasm, carry their own DNA. So the babies that Cohen’s group made by cytoplasmic transfer had inherited DNA from two eggs and one sperm. That is, they carried genes from three parents.

  So this was yet another kind of genetic engineering, as Silver said. You could argue that these babies represented not one but two firsts: the first successes of gene therapy, and the first germ-line gene therapy ever done on human beings.

  After Cohen, the next speaker was Rick Adler, the team’s microscopist. He explained that he had been examining the eggs in their cytoplasmic transfer project with the new wonder tool in the lab, the confocal microscope. Twenty-five years before, the wonder tool had been the electron microscope. But with that, you could only look at a dead, stained cell. With the confocal microscope, you could look at a live cell, and because the imaging is done by a computer, you could see things right away.

  As Rick explained all this, there was a little hmmm of interested approval. “Turn the lights down a little bit more.”

  When Rick looked at the embryos in their cytoplasmic transfer project, he said, he noticed that the blebs, the fragments around each embryo, were extremely “hot.” “Lit in red, in this picture. Lots of mitochondria there. This is the embryo I happened to be looking at when Cohen walked by the room,” Rick said. “And he went bananas.”

  During a break, I went out with Silver to an upper deck of the Galaxy, aft, and in the Orion Lounge, Silver told me why Jacques Cohen had gone wild.

  “The question is, what allowed these women to get pregnant,” Silver explained. Through the injection of cytoplasm, only a small percentage of the mitochondria entering the fertilized egg came from a third party. But in the embryo that Rick had examined, about fifty percent of the mitochondria had come from a third party. That was why the confocal microscope image had shocked Cohen. “The only way that could happen is they’re being selected,” Silver said. The mitochondria from the donor mother had been selected in the egg as the embryo grew, while the mitochondria from the birth mother had been rejected. In other words, it was the mitochondrial genes of the third party that allowed that baby to be born.

  “So it looks like gene therapy!” Silver cried. “They’re scared to death, because it’s genetic engineering and Jacques knows it. And the whole world thinks that’s horrible, horrible, horrible. And maybe it’s not so horrible, horrible, horrible. And that’s maybe one reason Jacques wanted you here—to say that maybe it’s not horrible.”

  During the next break, I found Cohen and Silver and a few others standing by the door to the auditorium. “This is genetic engineering!” Silver was saying, in a voice like a headline.

  “We keep trying to avoid the term,” said one of the young scientists in Cohen’s group, Jason Barritt.

  “Oh, it’s genetic engineering. That’s correct,” said Cohen.

  “Congratulations!” Silver cried, again in sixty-point type, and shook Cohen’s hand.

  “You have changed the genetics,” Cohen continued, cautiously. “But not the nuclear genetics. Which is what everyone is worrying about. These are very subtle changes.”

  Cohen was reminding Silver that he had injected only cytoplasm, not a nucleus, into the egg. The third-party DNA came from the mitochondria, not the nucleus. The distinction mattered very much to Cohen. If the procedure they w
ere performing was germ-line gene therapy, then it was banned by international agreements. But since Cohen had injected cytoplasm that contained mitochondria that in turn contained DNA, he felt that he had not broken the ban.

  Silver himself seemed to think that was just quibbling. He was not interested in arguing whether or not Jacques had broken a ban. He was interested in the next step. He said he could imagine that giving the egg an injection of mitochondrial DNA from a healthy young woman could produce a baby with more energy, better endurance. He urged Cohen to select for those qualities in the cytoplasm donors.

  Cohen was surprised. “So you think that we should actually select for…?”

  “If you need an egg donation,” said Silver, “you might as well choose the best you can.”

  So now we were moving in one easy step from germ-line gene therapy as a medical treatment to germ-line gene therapy as an enhancement: the deliberate attempt to engineer better and fitter human beings.

  Young Jason Barritt noticed me scribbling away, leaning against the wall. “He’s writing his next book!” he warned Cohen.

  “I’ll choose stupidity,” Cohen said to me, lightly. “Can you make a note of that? Ignorance is bliss.”

  “Your next book,” Jason said to me again, with a significant glance at Cohen.

  “That’s OK,” Cohen assured him. “He’s under contract.”

  “There’s an invisible zipper right here,” I said, idiotically, running a finger across my lips.

  “It’s the hand,” Jason said. “I want the hand to slow down.” He reached over and tapped my hand as I scribbled in my notebook. He was worried about the media, he told me. “No offense,” he said.

  “He’s not the media,” said Silver.

  Cohen said he thought bioethicists’ resistance to their work was probably going to get worse, not better. “I went to the Internet again to get slides for this week’s talks,” he said. “The anger is amazing. And these people are—” A small smile and nod to Silver.

  “—our colleagues,” Silver said.

  They talked for a while about a few of the famous biologists who hated Assisted Reproductive Technology, ART.

  “This started a long time ago,” Silver said. “People rejected medicine. People rejected vaccines!” he said, speaking in the tones of one of Galileo’s comforters.

  “But we don’t really want to be the ones rejected,” said young Jason.

  That night at dinner, Cohen, Silver, and most of Cohen’s team and guests sat at Table 600 in the corner of the Orion Restaurant wearing dark suits and evening dresses. Cohen had been invited to join the captain’s table for dinner, but he had chosen to dine with his team. Sitting at the center of the table, with Silver at his side, Jacques Cohen raised his wineglass.

  “To you,” he said to Silver. “Thank you for joining our group this week.”

  Everyone drank the toast. Then Silver raised his glass.

  “To more playing God!”

  Eighteen

  “My Husband, Doctor

  Frankenstein”

  I had thought I was getting away from gene therapy. Instead I had sailed right into it. If that operation of Cohen’s was the first genetic engineering of human babies, then it would have to be regarded as one of the most extreme tests of our bioethics. And when I went back to the Heywoods, I would see how complicated the ethics get even when we are talking about what might look like a very simple story at the edge of medicine.

  But while we are on the boat, and talking blue sky, I have to pause to tell a story that I think represents one of the greatest extremes of all.

  Genetic engineers like to say—I heard them say it several times on the Galaxy—that playing God with the fate of the human species is impossible. Genetic engineering is too expensive and labor intensive. There are billions of people on the planet. How could anyone ever engineer more than a small handful of fertilized human eggs? A dozen, a hundred, or even a thousand would be a drop in the gene pool. The drop would vanish without a trace.

  I first heard that argument made by Lee Silver in one of his classes at Princeton in the Lewis Thomas Laboratory, a few years before the birth of Dolly. I was sitting in the back of the hall, as usual. The average age in the room was twenty-one, Mary Shelley’s age when she published Frankenstein.

  At that time, I was fresh from my time in the Galápagos. Sitting in the back of the lecture hall that night, I realized that the conventional wisdom underestimates our power to influence human evolution.

  In the Galápagos, it did not take many finches to start a new line: All it took was one lost flock. A million years ago, a few birds were blown out to sea on freak winds, and landed on the bare new lava of the islands. There they were cut off from their kind. At first they were isolated only by geography. Then they were isolated by their genes. They evolved what is known in the jargon as reproductive isolation. They diverged, and diverged some more, and today there are a dozen species of Darwin’s finches.

  To create a new human species, genetic engineers would not have to engineer billions of babies. All they would need is to engineer reproductive isolation in a few babies. All they would need is fifty Adams and fifty Eves. No one could predict the fate of those hundred babies, of course, but by definition they would be a new species, as separate from the rest of us as Neanderthals, Homo habilis, and Cro-Magnon.

  A few days after I had that notion, I dropped by Silver’s office in Lewis Thomas and asked him what he thought of my idea. He listened for a few moments and said, softly and dramatically, “Shut the door.”

  “It wouldn’t be easy, but in theory it could be done,” he told me. “It’s a fantastic idea.” And on the spot, he thought of a way to do it. “There’s a case in mice,” he said. In 1972, in a certain lonely valley in Switzerland, the Valle di Poschiavo, Silver said, a biologist discovered mice that have only twenty-six chromosomes. Normal mice have forty chromosomes. The mice in that valley look exactly like normal mice, and they have exactly the same genes as normal mice, but a few of their chromosomes have shuffled and fused. They have the same encyclopedia, so to speak, with a few volumes mis-shelved or stuck together. “But the incredible thing is that these are new mice,” Silver said. “They can’t breed with other mice.” In the jargon of evolutionary biology, they are a cryptic sibling species—a hidden new line of life. They have evolved reproductive isolation.

  Lee thought that in principle, genetic engineers could do something like that to a very young human embryo, say a male. They could go in at the eight-cell stage and make pieces of chromosome 2 trade places with pieces of chromosome 13. They could shuffle three or four volumes of the encyclopedia. Then they could engineer the identical shuffle in the chromosomes of forty-nine more male embryos and fifty female embryos. When they grew up, those fifty Adams and Eves would be able to make babies only with each other. Their line would be cut off from the rest of the species, just like the mice in the lonely Swiss valley. Misplaced chromosome segments like these are known as chromosomal translocations. Evolutionists have studied translocations for years as one plausible mechanism in the creation of reproductive isolation and the origin of new species. Once reproductive isolation occurs, the myriad random mutations that take place in each generation can add up, and the isolated population and the main population slowly diverge.

  “That’s the way I would do it,” Silver said. “No reasonable person could be in favor of this happening. But biologically it could be done.”

  I thought that over. Then I called a few other molecular biologists. Each one thought it was a wild idea and on the spot each one thought of another way to create an isolated human species. Molecular biology was moving so fast that it was capable of experiments as outrageous as anything in the literature of science fiction. Naturally, I thought of that dark night in another valley in Switzerland, in 1816, when Mary Shelley laid her head on a pillow and dreamed her famous nightmare. She saw a young man, she wrote afterward, “a pale student of unhallowed arts,” kneelin
g beside a body that he had put together in secret. The body stirred, and the student ran off, hoping that the thing he had made would die again, praying that while he slept the strange spark he had lit would go out. “He sleeps; but he is awakened; he opens his eyes; behold, the horrid thing stands at his bedside, opening his curtains and looking on him with yellow, watery, but speculative eyes.”

  I also thought of the celebrated dark night in England in 1885, when Robert Louis Stevenson thrashed in his bed and cried out in horror. Frightened as he was, when his wife woke him up he was bitter and indignant. “I was dreaming of a fine bogey tale!” he said. In his dream, a doctor had mixed a potion and transformed himself into a murderer. That nightmare was the beginning of Dr. Jekyll and Mr. Hyde.

  No one could create a new species of human being in 1816, or change human nature in 1885. But now pale students had new tools. Early in 1995, the New York Times had run a story by William Stevens with the headline: “Evolution of Humans May at Last Be Faltering.” “Is human evolution ending,” the story asked, “…Or will humankind, armed with the tools of molecular biology, seize control of its own evolution?” I thought I knew the answer.

  Mary Shelley did not know anything about chromosome translocations, of course. She dreamed her dream several decades before the monk Gregor Mendel inferred the existence of genes in his monastery garden. So she built an adult from spare parts, rather than an egg from spare parts. Otherwise the two scenarios are essentially the same. In the novel, Doctor Frankenstein’s creature begs him to make him a bride: “My companion must be of the same species and have the same defects. This being you must create.”

  So much for the pieties of the One Hundredth Psalm: “Know ye that the Lord he is God: It is he that hath made us, and not we ourselves.”