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Speakers clarify science of cloning, stem cells

An international group that hopes to welcome extraterrestrials to Earth also claims that cloning would prevent future terrorism by making a Sept. 11-type attack futile because all the victims could be resurrected. Cloning the dead terrorists would allow them to be brought to justice, the group adds.

Rudolf Jaenisch, a founding member of the Whitehead Institute and an MIT biology professor, related this item (the group has testified before Congress) as an example of the bizarre emotional reactions that have been provoked recently by the possibility of human cloning.

Jaenisch spoke as one of three panelists at the ninth annual Catherine N. Stratton Lecture on Critical Issues on Oct. 22. The panel, which was moderated by MIT biology professor Richard O. Hynes, also included Harvey Lodish, a founding member of Whitehead and an MIT biology professor; and Helen M. Blau, the Donald E. and Delia B. Baxter Professor at the Stanford University School of Medicine.

"Stem Cells, Cloning and Gene Therapy: The Biology Behind It" laid out a clear picture of a confusing subject for the varied audience that filled the Tang Center's Wong Auditorium. Although the terms "stem cells" and "cloning" are widely used by the media, the panelists said they are rarely used correctly.

For the record:

  • Embryonic stem cells are taken from a five-day-old fertilized egg, a mass of around 200 undifferentiated cells called a blastocyst. The blastocyst, not yet implanted in the uterine wall, does not resemble an organism of any kind. Because these cells from the blastocyst may be tweaked to become any organ within the body, they show great promise for potential future therapies for a wide range of diseases and disorders.
  • Adult stem cells exist in all our bodies at all times, producing new skin, intestinal lining, red blood cells and even brain cells, but they are very rare and difficult to isolate because they look just like any other cell. Lodish's lab has made significant progress in identifying blood-forming stem cells. These adult stem cells found in bone marrow can be channeled to become fat cells, cartilage-forming cells or bone-forming cells, but so few have been isolated to date that Lodish has never seen more than a few in one place at one time.
  • Reproductive cloning creates new individuals and has been accomplished in seven species, including the sheep, mouse, cat, rabbit and cow. All have been cloned to create normal-looking, genetically identical copies of the original animals by sucking out the nucleus of one of the animal's cells, replacing it with a transplanted nucleus and placing the resulting embryo in a host mother.
  • Therapeutic cloning, in comparison, involves using embryonic stem cells to correct a disease. It does not involve creating a new creature, but focuses on prolonging an existing life.

Jaenisch has accomplished therapeutic cloning with mice. He took stem cells from a mouse with a version of "bubble boy" immunodeficiency disease, corrected their genetic mistake and transplanted them back into the animal, restoring normal immune function. "We have shown there is no biological barrier to using stem cells to correct a genetic defect," he said.

The same is not true of reproductive cloning. "Most, if not all, cloned animals are not normal," Jaenisch said. They may look normal, but hundreds of their genes are abnormally expressed, and the ones who have aged develop problems later in life.

He said the problem lies in the need for the transplanted nucleus to quickly activate the genes needed for early embryonic development, which, in the donated adult cell, are not "turned on" or readable by the cell. "In most cases, this fails and the embryo dies," he said. When it does result in a birth, the animal is often malformed - many are grossly overweight - or has an abnormal immune system or skeletal problems.

For these reasons, Jaenisch said he could not condone any attempts at human cloning. "At present, there is no way to predict whether a given clone will develop into a normal human being," he said.

Hynes pointed out that research on embryonic stem cells is currently restricted and proposals are on the table to further limit the work. Federal funding may not be used to create new stem cell lines, and there are only a handful of viable existing cell lines available to researchers.

While embryonic stem cell research is controversial and adult stem cell research is not, "all these possibilities should be pursued because we don't know enough about these stem cells and what they could be useful in treating," Blau said.

Gene therapy has come a long way in recent years but has a long way yet to go, she said. You could think of gene therapy as a novel form of drug delivery - "it's enlisting your own cells to produce the therapeutic protein to treat your own disease," she said. Unlike a regularly injected drug, the gene is constantly there, churning out the needed substance to treat high cholesterol, cancer or HIV.

Media coverage has focused on a Pennsylvania human gene therapy trial that killed a patient, shutting down other experiments. "One failure makes the headlines and holds back the whole field," she said.

Meanwhile, advances include the first successful treatment of children with "bubble boy" disease. "We learned how to engineer the stem cells and immunity was restored," she said. It turns out that the precise place where the transferred genes are integrated into the body is critical - one child in the trial developed cancer because the retrovirus used to insert the gene was placed next to a cancer-causing gene. The Pennsylvania case also focused on a mistake in the delivery system.

"We are just at the beginning of this line of research," Lodish said. "We need to figure out the basic properties [of the cells] that would allow this line of research to go forward." There are many technological hurdles to overcome, but the potential benefits are great: for Lodish, a cure for sickle-cell anemia, among other things.

The Stratton lecture series, sponsored by the MIT Women's League, honors Kay Stratton, wife of the late MIT President Julius Stratton.

A version of this article appeared in MIT Tech Talk on October 30, 2002.

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