Cellular Divide

Научная статья

Биология и генетика

To see the cells of a four-day human embryo, you stain them with a few drops of dye, slip them under a 20- to 40-magnification microscope and peer through the eyepiece. There they are: a hollow sphere of roundish balls, snuggled up against each other like sticky blueberries, pollen grains or vibrant red raspberry drupelets...



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Cellular Divide

Harvested From Embryos, Stem Cells May Cure Alzheimer's, Parkinson's And A Host Of Other Diseases. But Now The Cells Are At The Heart Of A War Pitting Pro-Life Purists Against Research

By Sharon Begley | NEWSWEEK                                         From the magazine issue dated Jul 9, 2001

They're not much to look at, really. To see the cells of a four-day human embryo, you stain them with a few drops of dye, slip them under a 20- to 40-magnification microscope and peer through the eyepiece. There they are: a hollow sphere of roundish balls, snuggled up against each other like sticky blueberries, pollen grains or vibrant red raspberry drupelets (depending on which stain you used). The 40 or so cells that constitute the embryo look a little fuzzy, dusty even, as if they had been rolling around on a dirty floor. But that, of course, is only the beginning of what you see. If you are a passionate right-to-life activist, you see in the cells an incipient human life, one deserving all the rights and respect of any other human, chief among those the right not to be destroyed and not to be used as a means to an end. If, though, you suffer from a currently incurable disease like Parkinson's or Alzheimer's, or love someone who does, then those cells look very different: they look like the seeds of hope, tiny miracles able to dance on the head of a pin.

In those two clashing views lie the makings of the latest embryo war. This time, it's not about abortion: the embryos whose cells, called stem cells, hold the promise of treating often fatal illnesses come not from clinics where pregnancies end but from those where they begin: in vitro fertilization (IVF) centers, which fuse sperm with eggs in a petri dish, and where "spare" embryos, too numerous to implant in the womb of the would-be mother, are otherwise discarded. Even though stem cells do not come from aborted fetuses (which are defined as older than nine weeks, with a shape and incipient organs), the moral and theological issues inherent in using human embryos in research press the same hot buttons. As a result the White House, which hoped it had done its right-to-life duty by pulling financial support for organizations that offer abortion counseling overseas and by supporting every piece of pro-life legislation introduced in Congress, has been dragged into the heart of an issue it very much hoped to avoid.

Sometime in the coming weeks, President George W. Bush is expected to decide whether to allow federal funding for research on stem cells taken from human embryos (following story). So far, he has remained true to his campaign stance opposing the research. In February he ordered a review of the Clintonian compromise under which federal money could be used to conduct such research, but not to obtain the embryonic cells in the first place. And this spring the administration canceled the inaugural meeting of a National Institutes of Health (NIH) committee that was to review applications for federal grants to study human embryonic stem cells. As long as Bush puts off a decision, the status quo--under which the research has come to a virtual standstill except in labs funded by biotech firms and other private money--will continue.

That infuriates an awful lot of politicians as well as ordinary folks who have decided that "pro-life" need not mean "no stem-cell research." In recent polls, 57 percent of abortion opponents have said they support embryonic stem-cell research. So have 72 percent of Roman Catholics. Sen. Orrin Hatch, as anti-abortion as they come, argues that "a frozen embryo stored in a refrigerator in a clinic" just isn't the same as "a fetus developing in a mother's womb." Former Florida senator Connie Mack, a pro-life Catholic and a Republican, has broken with his church and his party to support the research. "For me, as long as that fertilized egg is not destined to be placed in a uterus, it cannot become life," he says. But it can, perhaps, bestow life. "Anyone who would ban research on embryonic stem cells will be responsible for the harm done to real, alive, postnatal, sentient human beings who might be helped by this research," argues biologist Irv Weissman of Stanford University. "Opponents are sacrificing these people to keep from destroying embryos in fertility-clinic freezers" that will be thrown out anyway.

The cells that make up days-old embryos embody a world of potential. Four days after fertilization, the embryo is a hollow ball of cells called a blastocyst. Cells in the outer layer are destined to become the placenta. Those in the inner layer have not yet decided what they will be when they grow up: they are "pluripotent," able to differentiate into any of the 220 cell types that make up a human body, from the kidney, heart and liver to the skin, neuronal and pancreatic. These are the famous embryonic stem cells. For a few short days they are blank slates waiting for destiny (or the complex interplay of genes and biochemistry) to write their future.

And that is the source of their power. A decade ago research on lab animals revealed that stem cells taken from animal embryos are astoundingly versatile. They grow in the lab, proliferate like rabbits and turn into specialized cells such as neurons. But no one had turned the same trick with human cells. Then, in November 1998, researchers at the University of Wisconsin at Madison and at Johns Hopkins University announced that they had independently cultured stem cells taken from human embryos. In particular, they had stopped human embryonic stem cells from differentiating and, instead, kept them merrily growing in lab dishes while maintaining their pluripotency. It was as if someone had fired the starter's pistol. The next month John Gearhart, the lead Hopkins scientist, testified before Congress that embryonic stem cells might one day treat Alzheimer's disease, Huntington's disease, stroke and spinal-cord injury, as well as diabetes and muscular dystrophies: in each case, stem cells would be coaxed to turn into the appropriate cell and transplanted into a patient. By last December, Gearhart and Geron Corp., which funds his work, had figured out how to turn human embryonic stem cells into 10 kinds of cells, including heart muscle, skin cells and the immune system's T cells. Last week they were up to 110. "We have the technology to make infinite quantities of literally all cellular tissue in the body," says Geron CEO Dr. Thomas Okarma.

One early hope--that embryonic stem cells could be used to seed organ farms, growing livers, hearts and other body parts--is fizzling, however. Organs have intricate structures, with ducts and valves everywhere, and so will probably be tough to grow outside a body. Stem cells transplanted into a patient, however, are another story. In the two years since the discovery that human stem cells can be grown in the lab, their potential has only expanded, according to the NIH. Injecting stem cells into a liver could produce new liver cells, rejuvenating an organ decimated by cirrhosis or hepatitis. Stem-cell therapy might cure rheumatoid arthritis and osteoarthritis by replacing wrecked cartilage; it could supply new skin to treat life-threatening burns. Stem cells coaxed to produce cardiac muscle cells could replace cells damaged by chronic heart disease. "It is not unrealistic to say that [stem cell] research has the potential to revolutionize the practice of medicine," says Dr. Harold Varmus, former NIH director. How soon? Okarma guesses that clinical trials in which cells grown from human embryonic stem cells are implanted into patients are at least three years away.

The NIH, the chief supporter of biomedical research in the United States, has yet to award grants for studies using human embryonic stem cells. Some research is underway--Wisconsin has shipped its cells to some 30 research groups--but it is all privately funded, and therefore subject to minimal government oversight. Several researchers have told NEWSWEEK that since "spare" embryos are often inferior, and thus might not harbor healthy stem cells, some biotech firms are recruiting anonymous "gamete donors" to provide sperm or eggs. The former fertilize the latter. Presto: embryos to order, and to harvest stem cells from. The Biotechnology Industry Organization says it is unaware that any company is creating embryos in order to experiment on them. Another problem is that private companies are more likely than academics to hide their failures. And any therapies they develop, warns Dr. Evan Snyder of Harvard University, "will be exceedingly more expensive than you get with federally funded research."

So far, stem cells have proved a godsend to rats and mice, at least. Transplants of embryonic stem cells have enabled animals that suffered spinal-cord injuries to move their legs and partially support their body weight: the stem cells, taking a cue from their new surroundings, morphed into neurons. The cells have enabled rats that suffered strokes in the brain's motor cortex to move again: the cells home in on the lesion, mature into neurons and form the connections necessary for movement. Rats with the rodent versions of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (Lou Gehrig's disease) improved somewhat.

In a big surprise, scientists have discovered that even cells that seemed irrevocably committed to one job were capable of a midlife career switch. They have long known that many kinds of tissue include adult stem cells whose job it is to produce more cells of that kind: adult liver stem cells give rise to liver cells, adult skin stem cells give rise to skin, and so on. The cell divides, producing one differentiated cell (skin, say) and one stem cell, thus maintaining its biological seed corn. But lately, "multipotent" adult stem cells--capable of turning into more than one kind of cell--have been popping out all over. In mice, adult bone-marrow cells have produced neurons, liver cells, lung cells and gastrointestinal cells. When implanted into the hearts of mice that had suffered heart attacks, adult stem cells from bone marrow developed into cardiac cells and replaced damaged tissue. Last August, Ira Black of the Robert Wood Johnson Medical School reported that he had gotten bone-marrow stem cells from rats, which ordinarily become muscle, fat, tendons, ligaments or cartilage, to become neurons instead; implanted into rat brains, the cells survived and formed functional connections. "This overturns long-hallowed dogma," says Black. "We can induce adult stem cells to become novel cell types, such as neurons."

If human stem cells are equally versatile, "it raises the possibility that all of us are harboring the seeds of our own self-renewal," says Black. Last autumn, researchers announced that stem cells in human bone marrow had been transformed into neuronal cells. Adult blood stem cells seem able to spawn both brain and bone cells. "Stem cells from one tissue, like bone marrow, can actually be reprogrammed into cells that can repopulate muscle or brain," says Dr. Jeffrey Leiden, who recently left Harvard to become chief scientific officer for Abbott Laboratories. "That was completely unexpected, and it really opened up the number of diseases that can be treated by using adult stem cells." Humans also have adult blood stem cells, liver stem cells, neuronal stem cells and the like--all able to produce only that kind of cell but, still, produce it they do. "There are lots of studies, with more coming out, showing that you can take cells from one part of the body, grow them in culture, transplant them to another part of the body, and they turn into cells of that part of the body," says biologist Fred Gage of the Salk Institute.

To opponents of using embryos, this ends the debate. Why "kill anybody," as Sen. Sam Brownback put it, referring to stem cells from IVF embryos, when you can instead tap into willing adults with hardly more fuss than drawing blood? But adult stem cells may not live up to their name. They seem to proliferate more slowly than the embryonic ones, and so might not provide an ever-renewing source of new cells to replace those lost to, say, arthritis. Also, the studies on human adult stem cells may be flawed, says Gage. One biologist even calls them "crap science": although scientists think they induced bone-marrow cells to become brain or bone cells, in fact precursor cells of those tissues might have been present in the bone marrow all along. "No paper shows definitively any adult stem cell in humans turning into anything else," says Stanford's Weissman. "Looked at carefully, a lot of the claims have fallen apart." Last month, in fact, Margaret Goodell of Baylor College of Medicine backed away from her 1999 claim that she induced human muscle stem cells to become blood cells. "It's baloney that adult stem cells are all we need to make regenerative medicine real," says Okarma. A new NIH report concludes that embryonic stem cells may be superior to the adult variety.

Which is why scientists covet the six or so colonies of human embryonic stem cells growing in labs around the world, says Dr. James Thomson, whose Wisconsin lab started one of the first colonies. These lines might provide endless quantities of stem cells, obviating the need to harvest more embryos. "You can imagine a system where you don't have to keep going back to embryos," says Harvard's Snyder. But until enough such cell lines are established, Thomson says, "if the destiny of embryos at IVF clinics is to be thrown out, and couples are willing to donate them to research instead, it's hard for me to believe that throwing them out is a better ethical decision."

We have more questions than answers about the medical benefits of embryonic stem cells, either as the salvation of people with incurable diseases or as sources of knowledge about tragedies like birth defects. (Gearhart's original motivation for establishing a line of human embryonic stem cells was to discover what goes so wrong in a fetus as to cause Down syndrome.) It may indeed turn out that doctors will be able to work therapeutic magic with stem cells derived from adults. And it may turn out that embryonic stem cells will fall short of their promise. But we won't know either of those if American research on embryonic cells remains effectively off limits. That may be the most tragic consequence of squelching what is, more than anything, a quest for knowledge. We simply don't know how embryonic cells might help people who are suffering and dying today. By banning the research, we uphold the most extreme view of the sanctity of life, but at a price: foreclosing the possibility of doing all we can to improve the lot of the living.


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