||Jueves 26 de Mayo de 2005, Ip nº 110
|How to Farm Stem Cells Without Losing Your Soul
Por Clive Thompson
William Hurlbut clicks his laptop, and an x-ray pops up on the projection screen behind him. It's a picture of a tumor in a woman's ovary - a ghostly blob floating near the spine. In the middle are several strange, Chiclet-shaped nodules. "Those white opacities," Hurlbut says, "are actually fully formed teeth."
A few audience members blanch. Though we're in an ordinary conference room in Rome, it feels like church. The seats are filled with some of the Vatican's top thinkers, including a dozen men in clerical dress, a nun in a flowing brown habit, and a Dominican priest whose prayer beads quietly clatter. Hurlbut, a bioethicist from Stanford, has traveled here to tell them about a new way to create human embryonic stem cells.
As you might expect, the Vatican is vehemently opposed to embryonic stem cell science. President Bush is also wary, and two years ago he all but banned federal funding for it. But most medical scientists remain convinced that stem cells hold the key to a new kind of healing: regenerative medicine. Embryonic stem cells are pluripotent, meaning that they have the ability to develop into any type of human tissue. If that capacity could be harnessed and directed, injury and disease need no longer be crippling. For example, new neurons grown from stem cells might reverse the damage from Alzheimer's and repair severed spinal cords. But the research requires growing - and destroying - embryos in the lab. Hurlbut, however, claims he has a method for harvesting embryonic stem cells without killing human embryos.
The proof is projected on the screen. The x-ray shows a teratoma, a naturally occurring tumor that grows from an egg or sperm cell. Like an embryo, a teratoma produces stem cells. But the teratoma does not have the right balance of gene expression to create a fully integrated organism. So it grows into a dense ball of teeth, hair, and skin, a ghastly grab bag of organs like some randomly constructed Frankenstein. Hurlbut points to the x-ray. "They're about the ugliest thing in medicine," he says, "but they might offer us a solution to our stem cell dilemma."
In a bit of diplomacy that may satisfy both the scientists and the theologians, Hurlbut advocates genetically altering cloned embryos so, like a teratoma, they wouldn't have the DNA necessary to become viable humans. For the first few days of existence, they would grow normally and produce stem cells, but then die when a critical embryonic component - say, a placenta - failed to emerge. "They would have no coherent drive in the direction of mature human form," Hurlbut tells the crowd. "It's analogous to growing skin in a tissue culture. Such an entity would never rise to the level of a human being." You could grow them in vats, kill them at will, and never risk offending God. As both a medical doctor and a deeply religious Christian, Hurlbut borrows from each side: It's a theological breakthrough in the form of a scientific technique.
When he wraps up his presentation, the applause is long and loud. The priests chatter about the idea as they storm the cappuccino stand outside the conference room. "A number of Catholic thinkers are very open minded on this. It might not have any moral red flags. It might work," says Father Thomas Berg, a senior fellow at an ethics think tank called the Westchester Institute, who flew to Rome from New York for this two-day conference. Father Gonzalo Miranda, bioethics dean at Rome's Regina Apostolorum Pontifical University, tells me that Hurlbut could be the first scientist to break the logjam over stem cells: "He's humble, and he cares about ethics."
I ask Miranda whether Vatican leaders would really support the creation of entities that are almost human but not quite. "The hypothesis is not absurd," he says. "I think if they understand it, they would accept it." The priests are forming into little groups to discuss the idea. Seeing this, a severely jet-lagged Hurlbut finally comes to life. "For the first time," he says, grinning, "I think we can really do this thing."
Central to this debate is the perennial question: When does life begin? Science and religion have radically different answers. Scientists know that nerve and brain cells emerge shortly after conception. As a consequence, stem cell researchers generally agree that research should be done on embryos less than two weeks old. "Up to 14 days, you don't have a creature with a brain in it, so you can't even consider it to be, say, brain-dead," says Michael Gazzaniga, who heads Dartmouth College's program in cognitive neuroscience. "If you accept that, then there's no problem using embryos for research." The premise here is that the brain makes a person a person, a tradition that stretches back to Descartes' "I think, therefore I am."
Christian critics have a more clear-cut view: God endows every embryo with a soul at conception. So intentionally destroying an embryo is murder - even if it's only one-cell big. Theologians typically define the embryo in terms of its human "trajectory." Since every fertilized egg cell has the inherent potential to become a fully formed adult, they argue, interrupting that process at any point - from conception to birth to nursing home - is to disrupt a sacred process.
Hurlbut has sided with pro-life theologians ever since finding faith in his twenties. (He describes himself as a "generic Christian" who goes to church at a variety of services.) "This idea that an embryo becomes a person only at day 14 is truly pseudoscientific," he says. "It's completely arbitrary." He's a vocal opponent of abortion, a position that hasn't won him many fans on the Stanford campus, where he helped develop the university's bioethics curriculum in 1989. "I've gotten a lot of heat," he says. "I can't say I've liked it."
Ironically, Hurlbut's idea came about not in spite of his piety but because of it. Instead of dismissing the theological concept of an embryo's trajectory to humanhood, he seized it, seeing a scientific opportunity. Would it be possible, he wondered, to engineer embryos that didn't have human potential yet otherwise behaved normally?
Last summer, Hurlbut read about an experiment by Janet Rossant at the University of Toronto. Rossant created mouse embryos with DNA lacking in CDX2, the gene responsible for forming the trophectoderm, or skin on a blastocyte, which is the early form of an embryo. These developed normally at first, and Rossant extracted usable stem cells from them. But when their trophectoderms failed to form, the embryos died. Their life path, Hurlbut argues, showed only a "partial trajectory," and thus they were never capable of developing into mice anyway. Could a similar thing work in humans?
Hurlbut began corresponding with colleagues to ask about the technique's feasibility in humans. He showed me a letter from Rudolph Jaenisch, a leading MIT gene scientist, agreeing that it was "entirely possible with current science" and worthy of consideration. Evan Snyder, director of the Burnham Institute, a major center for stem cell research in California, is also intrigued by the idea and told Hurlbut he'd be willing to repeat Rossant's study to help verify that it's a viable alternative. "Give me a couple of mice and some grad students," he says, "and I could check it out for $200,000 or less."
Once Hurlbut determined that the science showed promise, he began courting high-powered religious leaders, including William Levada, the Roman Catholic archbishop of San Francisco, urging them to take a look at this new way of generating human stem cells. Levada sent a letter to Bush urging him to take Hurlbut's ideas seriously. "This proposal offers hope," he wrote, "that there may be a solution to an area of great challenge and controversy."
As promising as it may be, Hurlbut's line of reasoning leads to some hair-raising ethical conundrums. Imagine that scientists could engineer an embryo so that it would grow into an entire body, minus the cerebral cortex. Could scientists then kill it and use its parts to eliminate the wait for donated organs? As the debate over Terri Schiavo demonstrated, many religious thinkers regard people with minimal brain function to be fundamentally human. So where should the line be drawn when it comes to building "minimal" embryos? Could Hurlbut's non-embryos be considered humans who had been sadistically engineered to be disabled at conception? Is an embryo-like entity a person, normal for its first few days of development, only to be killed off in a form of genetic murder?
Hurlbut, a member of the President's Council on Bioethics, defended his idea at a March meeting of the group in Washington, DC. I watched from the gallery on the second floor of the Sphinx Club, where it was held.
The council was created in 2001 specifically to guide stem cell policy. Its other members include some of the most influential conservative ethicists in the US. There's Leon Kass, the imposing University of Chicago bioethicist who was appointed chair by Bush; Francis Fukuyama, the worldly Reagan-era pundit and author of The End of History and the Last Man; and Charles Krauthammer, the acerbic syndicated columnist and one of the first well-known neocon thinkers.
The meeting started off civilly, but when Hurlbut's proposal came up for discussion, the tone turned harsh. Krauthammer, in particular, said the concept made his skin crawl. "It's repugnant and weird and somewhat human - a border attempt to produce a human," he said. "It's an attempt to produce a human that went wrong. A teratoma is a tragedy. I don't think we should be producing tragedies." Paul McHugh, the psychiatrist in chief at Johns Hopkins, agreed with Krauthammer. "I share the idea that it's a kind of pollution of the human genome," he said. "There is something morally creepy," shuddered Michael Sandel, a Harvard professor of government, "about genetically engineering a mutant embryo-like being."
As the members blasted away, Hurlbut stewed. But when it was his turn to speak, he launched into a high-minded defense of his altered embryos. He acknowledged they are "unbeautiful." But so, he noted, is disease. "We do things in medicine that are strange and unintuitive," he said. "We give people a dose of disease for vaccination. We grow sheets of skin from bits of foreskin. We do things that are not easily and intuitively aesthetically pleasing for a greater good, which is healing."
By the end, the council wasn't convinced, but most agreed that Hurlbut's idea should be carefully tested on animals. This is where most of the priests in Rome ended up as well. They support Hurlbut's concept, but only because they feel they have no other option. "If Brave New World weren't already here, I wouldn't go near this," said Father Berg, who witnessed the drama from the audience. "But because Brave New World is here, maybe this is a way out."
A week after Hurlbut's visit to Rome, I meet with him for dinner at an Italian restaurant near his home in Woodside, California. He looks exhausted. After visiting Italy and DC, he flew to Massachusetts for a meeting with Governor Mitt Romney, and in a few days he'll pitch his idea on The O'Reilly Factor. All the travel has kept him from his wife, who at the moment is in her final days of pregnancy. "Erica feels like I'm never around," he tells me morosely, as he tackles a grilled-lamb salad.
Over the course of the meal, I realize that it's not really the barnstorming that's getting him down - it's the blowback. "I'm not a political person. I wasn't brought up to be in the press. I didn't seek out the spotlight," he says. "I was raised to believe that old rhyme: 'Fools' voices and fools' faces are often seen in public spaces.'" He seems genuinely stunned to discover that his real fight isn't with either the Vatican or even the President's Council. Ironically, his biggest opponents are those he says he's trying to help: embryonic stem cell researchers.
It turns out most scientists don't want Hurlbut's "help" in creating a more moral stem cell line. In December, the New England Journal of Medicine published an editorial by three leaders of the Harvard Stem Cell Institute attacking Hurlbut's proposal. "We believe that it is flawed," the authors argue, claiming that his logic is "ill defined." What's more, the article asserts, the technique would never work. Even if scientists managed to successfully create the altered embryos and harvest stem cells from them, they would still have to reach into those stem cells and reinstall the gene they removed at the outset, otherwise the stem cells would themselves turn into doomed, useless mutants. The entire procedure, says Douglas Melton, lead author and codirector of the Harvard institute, "is incredibly difficult to do." Others are more hopeful. "It's possible," says Andrew Fire, a leading genetics expert at Stanford. "Complex, but it's possible, certainly."
The critics freely admit their concerns aren't merely scientific - they're also political. Melton and his Harvard colleagues worry that Hurlbut's Christian-friendly proposal is a wolf in sheep's clothing, that the religious right will promote it as the only ethical path for research and push politicians to redirect federal research money into Hurlbut's technique. "Some have suggested that this is a device to force a de facto moratorium in the field," Melton says. "You'd spend millions trying to perfect this new thing, instead of doing the work with what we know now." Hurlbut scoffs at the notion that his proposal is a diversion. "We're talking about an issue that's tearing the country apart. Suppose it costs $100 million to solve this?" he asks. "It'd be worth it."
Other top scientists also worry about what happens if Hurlbut succeeds. Paul Berg, a Nobel laureate biochemist at Stanford, has encouraged Hurlbut to test his theory with experiments (in part to prove how hard it would be). Berg also vows to fight any attempt to divert funds from conventional stem cell research, and he quietly implies that Hurlbut is grandstanding: "I think Bill revels in the considerable publicity he has received by seeming to have found a way to calm the waters."
Hurlbut's supporters throw these bricks right back at the critics. They accuse stem cell research traditionalists of hoodwinking the public by promising cures they cannot deliver. "I've never been so disgusted in my profession as in the last five years," says Maureen Condic, a specialist in adult stem cells at the University of Utah. "They're saying, 'We're going to cure all these diseases; we're going to stop Michael J. Fox from shaking; Christopher Reeve was going to walk again. It's all lies." What Hurlbut's enemies won't admit, Condic says, is that many of them are not particularly interested in solving someone else's ethical problem. "They're like, 'I'm not going to have some Bible thumper telling me what to do.' They don't want to have any moral constraint at all, which is why they're terrified of Bill's success," she says.
For his part, Hurlbut is particularly incensed that his detractors keep oversimplifying his proposal. They maintain that the experiment on mice - knocking out CDX2 - wouldn't work in humans. Hurlbut insists he's never claimed it would. He says he cited CDX2 only as an example of what's possible; in humans, he suspects, you'd need to knock out some other gene, and only experiments will figure out which one.
Will the experiments ever run? The religious approval is growing. So the trail ahead must now be blazed by scientists. The challenge, Hurlbut has discovered, is not in charting a way forward that respects the moral qualms of the religious. The challenge is in getting scientists to take the high road.
4 Ways to 'Ethically' Harvest Stem Cells
A draft paper by the President's Council on Bioethics surveys four ways to derive embryonic stem cells without destroying human embryos. The goal: Be practical but "ethically uncontroversial." - C.T.
1. Alter Embryonic Cells
Proposal: Take human DNA and remove the genes an embryo needs to fully develop. Create embryos with the altered DNA. They will produce usable stem cells but die soon thereafter. Spiritually speaking, Hurlbut argues, these almost-embryos are not human, so harvesting their stem cells poses no moral dilemma.
Pro: Many religious leaders are enthusiastic. If the source isn't human, it doesn't have a soul.
Con: The genetic manipulation is very difficult.
2. Rescue Embryonic Cells
Proposal: Embryos are considered dead when they stop dividing. But it's possible to remove healthy stem cells from a dead embryo - think organ donation.
Pro: Technologically simple. And there's a steady supply from in vitro fertilization.
Con: No one agrees on what the embryonic "moment of death" looks like, so the procedure might kill viable embryos.
3. Biopsy Embryonic Cells
Proposal: Take an in vitro embryo just before it's implanted in the mother and remove a few stem cells. Such biopsies are routinely performed when parents want to verify their embryo doesn't harbor a genetic disease.
Pro: If the embryos aren't harmed, and the stem cells work, it's win-win.
Con: Ethically dicey. The procedure could lead to birth defects.
4. Reprogram Adult Cells
Proposal: Take a cell from an adult and regress it back to the pluripotent stage, an embryonic phase from which the cell can theoretically develop into any adult cell. Presto! Embryonic stem cells created without using embryos at all.
Pro: If the technique works as proposed, it would have zero ethical problems.
Con: Scientists can't even guide a stem cell development forward, much less backward. Worse, regress the cell too far back and it could turn into … a viable embryo. Whoops.
|| 01/06/2005. Wired Magazine.