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Stem cells - without the ethical division BY ERIC HAND St. Louis Post-Dispatch ST. LOUIS - There's stem cell research. And now there's research on making stem cells. Goals for the former include far-off cures for diabetes and severed spinal cords. The latter's goal is to create embryonic stem cells - without ever creating (and destroying) embryos. A human embryo, the size of a pinpoint, holds unique moral weight for some ethicists - and some constituencies. The embryonic stem cells that come several days later also have hefty potential for saving lives because they can turn into the specialized cells for all the body's organs. The conundrum has pushed some scientists down five carefully thought-out cellular and ethical paths, paths that could open up and allow stem cell researchers to have their cake and eat it, too: guilt-free embryonic stem cells. On Feb. 10, Sen. Jim Talent, R-Mo., gave the ideas a boost when, in a Senate speech, he withdrew support from an anti-cloning bill. He now proposes a $20 million prize to the first institution that harvests genetically matched stem cells without cloning a human embryo. Some scientists question the proposal, saying it's already easy to get stem cells for research: Use the tens of thousands of frozen human embryos destined for disposal at fertility clinics. The House has already passed legislation allowing such work. The Senate hasn't followed, so President George W. Bush's restriction still stands: Federally funded research can be done only on the two dozen or so usable stem cell lines created before Aug. 9, 2001. Some researchers say those lines are tainted. "The field of stem cell research has been crippled by the lack of quality stem cell lines," said Dr. Robert Lanza, the medical director at Boston-based Advanced Cell Technology Inc. While Lanza wants more stem cell lines available, he is nonetheless the scientist behind one of the alternative technologies. He says he can create stem cells from a one-cell biopsy, or live sample, of an embryo after it has divided into eight cells, something called a blastocyst. For about a decade, some in-vitro clinics have taken this one cell to test for genetic diseases. Lanza wants to let the cell divide in two. One would be for the test. The other then would be coaxed into stem cells. The seven-cell blastocyst would be placed back into the womb to develop normally. He published results in October showing he could do it with mouse embryos. Now, he says, he has done it with human embryos. He says that was easier. Those results have not yet been peer-reviewed or published. He acknowledges some problems - worries about the health of children born from an embryo missing one-eighth of itself. "How do you know 30 or 40 years downstream there's not some subtle consequence?" he asked. That's one reason the Catholic church could never accept the procedure, said Tadeusz Pacholczyk, education director at the National Catholic Bioethics Center in Philadelphia. Pacholczyk also wonders whether the one-eighth cell, left to develop, could become an identical twin. Lanza says it is unlikely that the cell has that total power. Robert George, a Princeton University politics and law professor on Bush's bioethics council, said the council has much skepticism for the biopsy approach - because of the health risks, and also because the stem cells would only be a genetic match for the person born from the surviving embryo. Stanford University physician William Hurlbut is promoting another idea, called altered nuclear transfer. Talent cited it as one of the promising techniques. In one ANT method, a gene is turned off in the nucleus of a skin cell, a gene that makes an outer cell layer that eventually becomes the placenta. That altered nucleus is placed in an egg cell missing a nucleus. The egg divides for a few days, creating stem cells, but dies when it can't develop the outer cell layer. A lab at the Massachusetts Institute of Technology announced in October in the journal Nature that it had done it with mice. Hurlbut says he has the support of moral philosophers, even some Catholic ones, but others find fault. "They're using cloning to essentially sabotage the development of human embryos - to deliberately create crippled embryos," Lanza said. Cloning has little to do with stem cells, but the two issues collide in the process of somatic cell nuclear transfer, where a skin cell nucleus is placed in an empty egg to create genetically customized stem cells. This is what South Korean researcher Hwang Woo Suk claimed to have done, but his work has since been discredited as a fraud. The method still holds promise because the created stem cells would be genetically identical to the skin cell donor and thus less likely to be rejected by the immune system. "We need a technique to get a genetic match," George said. ANT follows the same cloning process, but pre-emptively changes genes in the skin cell. When placed in the egg, Hurlbut says, the result is a like a tumor that makes stem cells, not alive in the human sense but a "biological artifact." Hurlbut says ANT is a broad concept that could include methods where other genes are altered, resulting in something that all ethicists agree is less than an embryo. "Above all else, ANT is a call for creative science," said Hurlbut, who is a member of President Bush's Council on Bioethics. Scientists seem to be answering that call, coming up with at least three other paths through the ethical maze. One process, called parthenogenesis, already occurs in species like frogs and turkeys. In parthenogenesis, the Greek word for "virgin birth," a female's egg divides without fertilization. The egg's 23 chromosomes are doubled. In humans, eggs induced to divide this way become cysts and die. Some scientists say stem cells harvested before the egg dies could be a good match for the donor woman. Others question the health of such stem cells because they lack a full set of chromosomes. Several years ago, scientists published results showing they gathered stem cells via parthenogenesis in primates. Lanza says the idea shouldn't be discounted: Starting with fewer chromosomes means stem cells would be more "generic" and less likely to be rejected by individuals' immune systems. Parthenogenesis is one of the types of stem cell research banned from federal funding. Another idea - still just an idea proposed by Columbia University professors - would aim to save still-living single cells from an embryo that stops dividing and dies in its early stages (four to eight cells). Those cells, like Lanza's biopsies, could be used to make stem cells. But the stem cells wouldn't be a genetic match for anyone, so their usefulness could be limited, George said. George said that everyone on Bush's bioethics council believes that an idea known as dedifferentiation will be the best in the end. Dedifferentiation is a reprogramming or turning back of the clock for cells so that they regain the power they had as stem cells. Newts do this, mysteriously, when their tails are cut off. The tail cells "remember" how to become stem cells again. The tail grows back. Last year, Canadian researchers identified some of the newt genes responsible for regeneration and are trying to find equivalent genes in humans. Harvard University researcher Kevin Eggan also has had some success. Last year, he published results showing that he had reprogrammed skin cells into becoming stem cells by fusing them with stem cells from one of Bush's approved lines. Going backward to create stem cells is easiest for people like George and Pacholczyk to accept because they believe human life is a continuum that moves forward at the moment an embryo is created. "We want science to be good science," says Pacholczyk, who is excited at the way ethics has stimulated science. Other scientists, such as Washington University's Steven Teitelbaum, believe that the treatment of incurable diseases is more important than a "pinpoint-sized ball of undifferentiated cells." Efforts like ANT are a diversion from already existing ways of getting stem cells from embryos, he said. It remains to be seen how Talent's proposal will affect a bill by Sen. Arlen Specter, R-Pa., which would open up frozen embryos for stem cell work and match the bill passed last year by the House. Specter has 40 co-sponsors. Senate Majority Leader Bill Frist, R-Tenn., has indicated he would push for a vote this spring. Lanza, who believes that life begins about a week after fertilization when an embryo is implanted in the womb, says existing and alternative approaches to harvesting stem cells could co-exist. Perhaps Specter's bill and Talent's proposal both will go forward. "This research needs to be pursued side by side," Lanza said. ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn