Eggan has also been itching to use cloning technology to create embryonic stem cells that could be used to model the development of various diseases, especially diabetes and ALS. The idea is that, by placing an adult cell from a diabetic, for example, into a human egg cell, the egg cell could turn back the clock of the adult DNA, or reprogram it, to its initial, pristine state. In this way, the development of the disease, too, could be traced back to its genesis. These cloning experiments (known as somatic cell nuclear transfer), in addition to being unambiguously nonpresidential, require a rare and precious starting material: healthy human egg cells. And those cells have been hard to come by.
In May 2006, Eggan’s lab received approval from Harvard to seek healthy human eggs from female donors, a first step toward using research cloning to create new stem cell lines. As soon as the lab got the green light, advertisements began to appear in The Boston Globe, The Harvard Crimson, and other local publications, seeking egg donors. The ads stimulated lots of inquiries, but actual donors? When asked recently, Eggan maneuvered his thumb and index finger into a big, fat zero. After nearly a year of recruitment efforts, not a single woman consented to donate her eggs for stem cell research.
Were they morally opposed to the research? Hardly, Eggan says. The problem, he believes, is that Harvard Stem Cell Institute researchers, following ethics guidelines, decided not to pay women to donate their eggs for research. Paying for human eggs, many bioethicists argue, commodifies a human resource; Sandel, for example, a proponent of both research cloning and embryonic stem cell research, opposes the idea of financial inducement for what he calls “human reproductive capacity.”
But this bioethically correct approach has run straight into a buzz saw of market economics. Fertility clinics typically pay women $5,000 or more to donate their egg cells, in a procedure that is time-consuming, medically arduous, and not without health risks. “People respond to our ad, but they don’t move forward,” Eggan admitted. “It seems like people really want to do it, but don’t feel they can justify the amount of time it would take without compensation. Needless to say, that’s been a source of considerable frustration.”
Faced with this litany of obstacles, you might think that Eggan’s lab represents another variation on the theme of delay. But that would underestimate the scientific ingenuity in solving problems. On the same day last January that conservatives in the House of Representatives tried unsuccessfully to criminalize the very experiments Eggan wants to do, he tapped his fingers on a thick manuscript sitting on his desk. “This is going out tomorrow,” he said, of a paper that ultimately made the cover of Nature last June. Its news was outlined, in schematic form, on the huge whiteboard in Eggan’s office. The drawing depicted a stunningly unexpected way to create embryonic stem cells—without using or needing an unfertilized egg.
“Everyone thinks we need oocytes to do somatic cell nuclear transfer,” Eggan said. Biologists have assumed that an adult cell could be “reprogrammed”—that is, cloned—only by an egg cell.
But Eggan and his colleagues went on to perform experiments suggesting that the mysterious elixir responsible for reprogramming was not geographically static but instead moved around inside the cell, depending on the phase of cell division. It tended to be sequestered in the nucleus but migrated out into the cell’s gelatinous exurbs, or cytoplasm, when the cell was about to divide. “Maybe at the one-cell or two-cell stage,” Eggan and his colleagues reasoned, “there’s still some of that stuff in there. . . .” And if they picked the right moment of cell division, when these powerful reprogramming factors were still floating around in the periphery of the cell, they might be able to use drugs to temporarily freeze the cell in the middle of division, stick in the needle of a micromanipulator to suck out the embryonic DNA, squirt in DNA from an adult animal, and then kick-start the process of reprogramming—hours, perhaps even days after an egg had been fertilized.
That is exactly what the team has demonstrated in mice, creating cloned animals from a fertilized egg. “You can [both] clone animals and make embryonic stem cell lines using this technique,” said Eggan, who is now testing the technique—nonpresidentially, of course—in human cells.
Eggan paused to write a number on the whiteboard: 90,000. “There are 90,000 IVF procedures every year in the United States,” he said. “Let’s say there are, conservatively, five oocytes from each cycle. That is maybe 450,000 eggs, right? A large proportion of those oocytes will get too much sperm. We’ll say it’s 5 percent.” He then paused to write another number on the board: 20,000. In IVF clinics, these overfertilized eggs are routinely culled after inspection and thrown away; their chromosomal irregularities make them unsuitable for implantation. “That’s like between 20,000 and 25,000 eggs that get thrown away in the U.S. every year at that stage,” Eggan continued. “They have abnormal numbers of chromosomes, and they would develop abnormally, and so you can’t use them. Even God doesn’t want these. But our method would allow them to be used. Twenty-five thousand eggs every year . . . ”
Each one, formerly doomed to be tossed away as medical waste, could be used to clone embryonic stem cells that might tell stories about common diseases and how they get started. As he headed out the door of the lab that day, Eggan barely contained his excitement. “It could,” he said, “change everything.”
That phrase, lamentably, has been used repeatedly during the six-year debate on alternative strategies. But it was nice, for a change, to hear it not from a politician or a pundit but from a scientist actually doing stem cell research.