Half Human, Half Cow, All Baloney

Britain has recently become the latest battleground of what appears to be a momentous struggle for the human soul. On one side are scientists who would usher in a brave new world of weird human-animal hybrids. On the other side are religious leaders and politicians of conscience who would draw the line once and for all against these perceived monstrosities. One of the most outspoken religious figures is Cardinal Keith O'Brien, leader of the Roman Catholic Church in Scotland. He launched an extraordinary attack during his Easter sermon on Prime Minister Gordon Brown. By supporting a bill that would legalize experiments in which scientists implant human DNA into a cow's egg cell, Brown was endorsing "experiments of Frankenstein proportion," said O'Brien. Facing mounting disapproval from the public at large, a rebellion in his own party and threats of resignation from three Catholic cabinet ministers, the prime minister was forced to retreat and allow Labour M.P.s to "vote their conscience" on the issue of animal-human embryos. Last month, while Parliament was debating the bill, the BBC broke the news that Newcastle University scientist Lyle Armstrong had successfully created just such a hybrid embryo.

The ensuing imbroglio, the latest battle in the tiresome war over stem-cell research, was great fodder for the tabloids. What neither side in this peculiarly British tussle understands is that the embryonic-stem-cell war is over, and the public is the big winner. A new technology has removed the entire basis of this longstanding dispute, though neither side is widely aware of it.

To understand what has happened, it's important to remember the original goal of the work of Armstrong and his biologist colleagues. They have never had any intention of creating hybrid animals or babies, of course, but rather to generate human embryonic stem cells, which have the power to turn into any type of human cell—liver, bone marrow, muscle, brain and so forth. To this end, scientists have tried to exploit knowledge of the molecular signals that naturally guide embryonic development. If scientists could master these signals, the thinking goes, they could one day have a means of transforming a clump of stem cells into perfectly compatible tissue for transplantation into a particular patient. Such a breakthrough would allow doctors to grow replacement organs or limbs, or replace brain tissue damaged by Parkinson's.

Many scientists have assumed that unfertilized eggs are an essential ingredient in the process of making patient-compatible embryonic stem cells. But human eggs are difficult to obtain and procuring them has raised ethical concerns. Armstrong was working to circumvent these problems by seeking an alternative method of making stem cells. He took an easy-to-come-by cow's egg, removed the genetic material and replaced it with human DNA from an ordinary skin cell. The resulting hybrid began behaving like a human embryonic stem cell.

Catholics reject standard embryonic-stem-cell work because it involves the creation and manipulation of human embryos. But Cardinal O'Brien and other Christian leaders object to this new research on different grounds: that the scientists were violating human dignity by combining human and animal ingredients in a weird ungodly hybrid life form.

While Armstrong and other cell biologists were pursuing the hybrid approach, other scientists have been taking a different approach to stem-cell research. They began with the assumption that a just few specific proteins in the unfertilized egg bear full responsibility for reprogramming a skin cell and causing it to become an embryonic cell. After all, it's proteins—not genes—that makes liver cells different from brain cells and muscle cells. Every cell in your body contains a complete and identical copy of your genome, but your liver cells may run one part of your genome's program while your muscle cells run another. In each case there's a prime mover—a single protein or set of proteins that makes a cell behave as a liver or a brain cell, or an embryonic cell. By decoding and isolating the prime movers of embryonic cells, stem-cell scientists hoped to do away altogether with a requirement for eggs of any kind. With the right proteins, they could kick start their own embryonic stem cell.

This work had just gotten underway when Ian Wilmut created Dolly, the first cloned sheep, in 1996. In recent years, sophisticated molecular tools of genomic research have allowed scientists to sift through hundreds of protein candidates for the embryonic prime mover. In June 2006, a Japanese group led by Shinya Yamanaka reported the first successful result with mouse skin cells, and between November 2007 and January 2008, Yamanaka's group and two American groups led by James Thomson and George Daley at Harvard University all reported the successful reprogramming of human skin cells into a state that is indistinguishable from human embryonic cells. Over the last several months, progress made along this new scientific path has been breathtaking. The laboratory of Rudolf Jaenisch at MIT has taken in the lead in developing therapies with this new technique in mice, demonstrating a cure for a mouse version of sickle cell anemia and alleviating the symptoms of Parkinson's disease in mice.

What these scientists can now do is essentially to take any type of cell and turn it into the equivalent of an embryonic stem cell—without needing embryos or egg cells. So what exactly are these new cells? Cells are fundamentally defined not by where they come from, but by their program of gene activity. In this sense, the new cells should be called embryonic stem cells. And since they are genetically identical to the person who provided the original sample, they are technically embryonic cell clones of that person. But scientists have discovered the power of words to elicit positive or negative emotional responses. "Clone" and "embryo" are words to be avoided. And so by consensus, the new cells are being called induced pluripotent stem cells.

Of course, there are still some obstacles to overcome before induced pluripotent stem cells reach the mainstream and can be tested in clinical trials. For example, the current technology is based on inserting reconstructed genes into the cell's chromosomes, which could induce unwanted side effects. But new methods are sure to be devised for introducing the prime movers without altering the cell's chromosomes. In a few years, the field of stem-cell research will incorporate these findings. Research on stem cells will continue apace, and the entire stem-cell controversy of recent years will fade away in Britain, the United States and everywhere else. The cow-human hybrid approach will merit no more than a footnote, as an also-ran technology, in the history of scientific advances. Of course, some diehard embryo research advocates—scientists and supporters alike—may have a hard time adjusting to life without a cause to fight. Partisans on both sides may find that the struggle for the human soul is a difficult habit to kick.

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