October 18, 2005

A More Moral Stem Cell?

Continued from page 1

By Erika Jonietz

In fact, PGD experts believe the procedure holds little additional risk beyond that inherent in IVF, since removing a single cell from the embryo does not significantly decrease the chances it will implant. However, they do doubt it will be easy to make Lanza’s technique work in humans.

"A human single cell is much more difficult to grow in culture" than mouse cells, says Santiago Munne, director of Reprogenetics, a private genetics lab that specializes in preimplantation genetic diagnosis. Currently, only 10 percent to 20 percent of attempts to induce a single cell from a human embryo to divide are successful, Munne says. If the cell does not divide overnight, it may die or undergo alterations that close the window of opportunity to do PGD analysis.

"If you are paying for PGD, you want every embryo diagnosed," he says. "I would never recommend this to a PGD patient of mine." And removing more than one cell from the embryo isn't an option either, Munne says, since that reduces the embryo’s viability by half.

Lanza says the co-culture technique should induce the separated cells to divide more reliably, obviating Munne's concerns and creating a new source of embryonic stem cells. His group has already begun studies using donated IVF embryos and existing embryonic stem cell lines; Lanza says it will take a year or two to complete these studies. Still, he acknowledges that it's not a sure bet: "We hope our approach can be perfected in humans," he says. "But a lot of people don't have time for us to work this out. I think it would be tragic not to pursue all of the options and methods that are available to get this technology to the bedside."

One of those other options -- reported in the second Nature paper -- is a technique demonstrated by MIT biologist and Whitehead Institute member Rudolph Jaenisch and Alexander Meissner, a graduate student in his lab. Called altered nuclear transfer, the method adapts a cloning technique researchers in Korea have already used to produce stem cell lines tailored to specific patients.

In the original technique, called somatic cell nuclear transfer, researchers transfer the genetic material from an adult cell into an egg stripped of its own DNA. The egg "reprograms" the adult DNA, creating an embryo with genetic characteristics identical to those of the donor. (The same technique was used to create Dolly, the world's first cloned mammal, and many subsequent clones.)

In 2002, William Hurlbut, a medical ethicist at Stanford University and member of the President's Council on Bioethics, proposed altering that process to produce pluripotent stem cells -- stem cells with the same potential as embryonic stem cells -- without creating human embryos. Hurlbut's idea involved altering either the nucleus of the adult cell, the cytoplasm of the egg, or both before they are joined in order to prevent the formation of an embryo. If researchers can succeed, says Hurlbut, "[it] could allow a true win-win solution to this -- not a compromise, but a solution."

In 2004, Hurlbut suggested that turning off a gene called CDX2, which is involved in the earliest stages of embryonic development and is required for the embryo to form a placenta and implant in the uterus, might be one way to prevent clones from developing into viable embryos. In their Nature paper, Meissner and Jaenisch showed that by turning off CDX2 in the nucleus of the donor cell before transferring it into the stripped-down egg cell, they could create an embryo that failed to develop properly -- but which could still be used create a normal embryonic stem cell line. "What one gets is a clone which has no chance to ever develop into a fetus," says Jaenisch. "But it still can make an embryonic stem cell."