Tailoring Therapies: Cloned human embryo provides stem cells

Scientists have for the first time used cloning to create human embryos that live long enough in a laboratory dish to have their stem cells harvested. The feat could set the stage for physicians to produce cells and tissues, tailored to a patient’s genetic identity, that can treat a wide variety of human illnesses. The accomplishment also provides a road map for how to clone a person, an even more divisive undertaking.

The new work, performed in South Korea, represents “a major advance in stem cell research . . . . It could help spur a medical revolution as important as antibiotics and vaccines,” says Robert Lanza of Advanced Cell Technology (ACT), a company in Worcester, Mass., that’s also investigating the promising stem cell strategy dubbed therapeutic cloning.

“However, now that the methodology is publicly available,” Lanza adds, “I think it is absolutely imperative that we pass laws worldwide to prevent the technology from being abused for reproductive-cloning purposes.”

While some fertility doctors and a religious cult have claimed success at creating a pregnancy via cloning, they’ve offered no convincing proof. In contrast, the South Korean research is being reported at the meeting of the American Association for the Advancement of Science in Seattle and will appear in the March 12 issue of Science. “This is reality,” says stem cell researcher John Gearhart of Johns Hopkins University. “Here is a bona fide, refereed journal saying that a human embryo has been cloned and a cell line derived from it.”

The South Korean team, led by Woo Suk Hwang of Seoul Nation University, initially collected 242 eggs from 16 volunteers. The investigators removed each egg’s chromosomes and, to replace that DNA, fused the egg with another cell from the same woman. They used cumulus cells, which normally surround eggs in the ovary.

Next, the biologists treated the eggs with two chemicals to trick them into dividing as if fertilized by sperm. The eggs then grew in the lab dish until they became blastocysts, which are balls of about 100 cells.

No human-cloning experiment previously reported in a scientific journal had generated embryos that survived this long. Once Hwang and his colleagues optimized experimental conditions, about 25 percent of the eggs reached the blastocyst stage.

For example, they settled on a 2-hour delay between fusing a cumulus cell with an egg and chemically activating the product. This window may give the egg time to reprogram the incoming DNA to act more like the DNA of a fertilized egg than like that of a cumulus cell.

The blastocyst stage is the point at which physicians performing in vitro fertilization typically implant an embryo in a woman’s uterus. Instead, the South Korean scientists harvested cells from the interior of their cloned blastocysts and discarded the remainder. From 1 of their 30 blastocysts, they obtained a line of long-lived cells that resemble embryonic stem cells in appearance and bear the same surface proteins. The harvested cells also demonstrated a hallmark of embryonic stem cells: When grown in lab dishes or transplanted into mice, these cells multiplied and produced many cell types, such as bone and muscle.

The Science report is a “solid paper. It’s repeating in human what has been done in mouse for a while,” says Rudolph Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Mass. “However, I would have liked to have seen the experiment done differently.”

Jaenisch says he was concerned because the researchers used an egg cell and a cumulus cell from the same woman instead of adding a different person’s DNA to replace the chromosomes removed from each egg. That decision left open the slim chance that the stem cells came from an egg that had retained its original DNA.

A detailed analysis of the DNA in the stem cells largely rules out that possibility, Gearhart and Jaenisch agree. Hwang’s team showed that the DNA in the stem cells had distinct paternal and maternal sets of chromosomes, as cumulus cells do, rather than the two copies of a single set of chromosomes that would result from an unfertilized egg cell forming a blastocyst.

Although ACT has yet to publish a report of a cloned human blastocyst, Lanza says that the South Korean success is “consistent with our own results.” Therapeutic cloning appeals to Lanza and physicians because cells made this way could have the same DNA as a patient’s cells do and thus avoid rejection after they’re transplanted.

Seeking a compromise that would permit this strategy to be pursued, many scientists have called for legislation that would ban cloning to produce a baby but allow the creation of cloned embryos to generate stem cells for research or therapies.

“The debate has been very polarized,” notes bioethicist Laurie Zoloth of Northwestern University in Evanston, Ill.

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