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Chinese fusion method promises fresh route to human stem cells

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  • Chinese fusion method promises fresh route to human stem cells

    [This message was edited by seneca on 08-14-03 at 12:26 PM.]
    Jake's Pop

  • #2
    Bit off-topic:
    With the mitochondria mentioning there, I just started to wonder, if there can be massive (mitochondria) genestring differences between kinds?


    • #3
      Cloning Yields Human-Rabbit Hybrid Embryo

      By Rick Weiss
      Washington Post Staff Writer
      Thursday, August 14, 2003; Page A04

      Scientists in China have, for the first time, used cloning techniques to create hybrid embryos that contain a mix of DNA from both humans and rabbits, according to a report in a scientific journal that has reignited the smoldering ethics debate over cloning research.

      More than 100 of the hybrids, made by fusing human skin cells with rabbit eggs, were allowed to develop in laboratory dishes for several days before the scientists destroyed them to retrieve so-called embryonic stem cells from their interiors. Although scientists in Massachusetts had previously mixed human cells and cow eggs in a similar attempt to make hybrid embryos as a source of stem cells, those experiments were not successful.

      Researchers said yesterday they were hopeful that the rabbit work would lead to a new and plentiful source of embryonic stem cells for research and, eventually, for medical use. But theologians and others decried the work as unethical.

      Some wondered aloud what, exactly, such a creature would be if it were transferred to a womb to develop to term.

      The vast majority of the DNA in the embryos is human, with a small percentage of genetic material -- called mitochondrial DNA -- contributed by the rabbit egg.

      No one knows if such an embryo could develop into a viable fetus, though some experiments with other species suggest it would not.

      Congress has been mulling legislation for years that would outlaw certain human cloning experiments, with some opposed to any creation of cloned embryos for research and others sympathetic to research uses as long as the embryos are not allowed to grow into cloned babies. No law has been passed, however, in part because of researchers' warnings that the proposed restrictions are so far-reaching that they would hobble development of new medical treatments.

      The new work, led by Hui Zhen Sheng of Shanghai Second Medical University, appears in the latest issue of Cell Research and was highlighted in a news report in the journal Nature. Cell Research is a peer-reviewed -- if little-known in the United States -- bimonthly scientific journal affiliated with the Shanghai Institute of Cell Biology and the Chinese Academy of Sciences.

      Some researchers yesterday said they were frustrated by the lack of details in the paper.

      The team said it retrieved foreskin tissue from two 5-year-old boys and two men, and facial tissue from a 60-year-old woman, as a source of skin cells. They fused those cells with New Zealand rabbit eggs from which the vast majority of rabbit DNA had been removed. More than 400 of those new, fused entities grew into early embryos, and more than 100 survived to the blastocyst stage -- the point at which coveted stem cells begin to form.

      The approach could help scientists wishing to mass-produce human embryos as sources of human embryonic stem cells. Stem cells can morph into all kinds of tissues and may be able to reverse the effects of various degenerative diseases.

      But to make cloned embryos, scientists need both normal body cells -- such as skin cells -- and egg cells, which have the unique capacity to "reprogram" the genes in body cells and make them behave as though they were embryo cells.

      Because human egg cells are difficult and costly to retrieve from women's ovaries -- and because human egg retrieval poses risks to the donors -- scientists have been wanting to know whether animal eggs may serve as well. A major question has been whether the remnants of mitochondrial DNA that typically remain in an animal egg would be compatible with the nuclear DNA contributed by the human cell.

      The new work suggests that the answer to that question is yes, scientists said -- though with a number of caveats. Most important, researchers said, the paper stops short of proving beyond a doubt that the stem cells retrieved from the hybrid embryos are truly capable of growing for long periods of time in lab dishes, and that they can turn into every known kind of cell.

      Even so, said Douglas Melton, a Harvard University cell biologist and cloning expert, the work is a big advance because it offers a new system for exploring the mechanisms by which egg cells get adult cells to act in embryonic ways. That could provide deep insights into human development, wound healing and tissue regeneration.

      He noted that although this is the first creation of a human "chimeric" embryo -- a reference to the fabulous chimera of Greek mythology, which had a lion's head, a goat's body and a serpent's tail -- it is not the first time scientists have blended human cells into lab animals. Some mice, for example, have been endowed with human brain cells or portions of the human immune system for research.

      The Chinese work, Melton said, is "extremely interesting, and I hope they pursue it."

      R. Alta Charo, an associate dean of law and professor of bioethics at the University of Wisconsin at Madison, noted that the work passed muster with Chinese ethics authorities, who had demanded, among other things, that the embryos not be allowed to grow more than 14 days.

      "Short of putting one of these embryos into a woman's body for development to term, I don't think this work harms anyone alive," Charo said.

      She said the experiments should force opponents of cloning research to identify more clearly than they have until now exactly where they would draw the line against human embryo cloning -- in effect: How human does an embryo have to be to have the moral standing these advocates confer on embryos?

      Richard Doerflinger, of the U.S. Conference of Catholic Bishops, said he felt certain that the human-rabbit embryos were human enough to deserve protections.

      "I think because all the nuclear DNA is human," Doerflinger said, "we'd consider this an organism of the human species."

      © 2003 The Washington Post Company


      • #4
        Experts doubt claim of rabbit-human clone

        By Steve Mitchell
        Medical Correspondent
        Published 8/15/2003 3:51 PM

        WASHINGTON, Aug. 15 (UPI) -- Although the recent claim by Chinese scientists that they created a cloned human embryo using rabbit cells made headlines around the world, cloning experts have many reasons to doubt the assertion.

        The skepticism stems from the fact that other groups have tried similar cross-species cloning experiments without success. Also, key data that would have substantiated the Chinese claim have not been provided. And researchers in China have gained a reputation for making bold claims about cloning and stem cells that, all too often, other scientists are unable to verify.

        As described in Cell Research, an obscure journal published by the Chinese Academy of Sciences, a group led by Huizhen Sheng of Shanghai Second Medical University inserted the nucleus or DNA material from human skin cells into an egg cell from a rabbit. The resultant rabbit-human hybrid developed into a human embryo from which Sheng's group claims to have obtained embryonic stem cells.

        The manuscript of the study has been circulating among the scientific community for more than two years but the top-tier scientific journals refused to publish it. Prestigious journals, such as Science, Nature and the Proceedings of the National Academy of Sciences, declined to publish the study because their reviewers -- scientific experts who advise journals on a study's merit prior to publication -- found it lacked standard data that should have been included. Requests by the reviewers for additional data from the Chinese researchers apparently went unfulfilled.

        Sheng could not be reached by UPI for comment by presstime, but she was quoted in a news article in Nature as saying, "It still may take a while for people to accept the work. But the scientific community has the right to question the details of the work and we have a responsibility to respond to them."

        Many scientists familiar with this line of research found Sheng's claim hard to accept.

        "It sounds a little too good to be true," said Dr. Robert Lanza, vice president of medical and scientific development at Advanced Cell Technology of Worcester, Mass., the only group to have produced a cloned human embryo legitimately (using human egg cells, not a rabbit's).

        "This flies in the face of existing scientific knowledge," Lanza told United Press International. His company has attempted to use rabbit egg cells to clone primates, a group that includes humans as well as their closest living relatives -- monkeys and apes -- and found it to be impossible, he said.

        "There are curious aspects to the data (and) I'm sure the entire scientific community will remain skeptical until it's reproduced," said Dr. George Daley, a stem cell researcher at the Massachusetts Institute of Technology.

        If it is authentic, the study would represent an exciting breakthrough because it would permit studying the phenomena of reprogramming -- converting an adult cell back to its infancy or embryonic stage, which could either be used to produce embryonic stem cells or directed to develop into a specific type of tissue, such as brain or heart. The technique also could prove useful as a conservation tool because scientists could then use rabbit eggs to clone endangered or extinct animals.

        Embryonic stem cells are valued for their ability to become any tissue in the body and scientists think one day they could be harnessed as treatments for various diseases. The resultant stem cells from a rabbit-human hybrid probably would not have any direct value in medical treatments due to concerns they could contain rabbit diseases or pathogens and unwittingly transmit them to people. But it would represent "an enormous experimental advantage" for studying reprogramming, Daley said.

        Pro-life and anti-abortion groups object to embryonic stem cell research because it requires the destruction of human embryos. However, if researchers could learn how to reprogram adult cells they could retain all the potential medical benefits and perhaps avoid the moral quandary involved. "That's the Holy Grail ... and this may be an important research tool for getting us there," Daley said.

        However, scientists remain doubtful the research will turn out to be valid. Lanza noted other groups have attempted similar experiments -- combining rabbit egg cells and DNA from other species -- and have been unsuccessful. In addition, several scientists who heard about the study before it was published attempted to replicate it in their own labs and none of the experiments was successful, he said.

        Advanced Cell has done extensive work in the field of cross-species cloning, using the technique to clone two endangered species successfully. One of the main technical barriers is that the egg cell carries DNA from a component of cells called the mitochondria, which has its own genetic material that is separate and distinct from the DNA in the nucleus. Mitochondrial DNA in the egg cell can negatively interact with the DNA of the species attempting to be cloned. This generally is not a problem in species that are closely related but it wreaks havoc in species that are evolutionarily distant.

        "When you try these cross-species experiments as soon as the evolutionary divergence gets too great cells cease to divide," Lanza said. "When you try combinations that are even slightly outside the family (of closely related species), you get this blockage."

        The general rule is if species are evolutionarily separated by more than 8-million to 18-million years, it is next to impossible, he said. Rabbits and humans fall well outside of that range, having diverged more than 80 million years ago.

        Even if the Chinese researchers did manage to overcome the barrier of evolutionary separation and actually produce a human embryo, scientists still have reason to doubt claims they obtained embryonic stem cells.

        They did not conduct the necessary experiments to show they had extracted true embryonic stem cells, Daley said. To be authentic stem cells, it would be necessary to show the cells were immortal or could divide indefinitely, and that they could give rise to all the different tissues in the body. Such proof -- which involves relatively straightforward and standard procedures -- was not included in the manuscript, he said.

        In addition, some scientists in the cloning field are wary of any research coming from China because a number of other manuscripts purporting bold advances in stem cell and cloning technology originated there, although most never have been verified.

        "There are lots of claims and rumors coming out of the mainland that are unsubstantiated," one researcher familiar with the Chinese research told UPI. "There are a number of manuscripts that have circulated that have never gotten published" because journals and reviewers doubted their authenticity, said the researcher, who requested anonymity.

        Still, both Lanza and Daley do not rule out the possibility the rabbit-human hybrid experiment could be valid.

        The inherent problems and past difficulties with such experiments do not "mean it can't be done, it just means there's a lot of skepticism," Lanza said.

        Daley agreed, noting breakthroughs in areas where others have previously failed happen often in science. On the other hand, "science is also full of initial claims of success that don't ultimately hold up to scrutiny," he said. "My sense is if this is as easy as the authors claim, other groups will quickly reproduce it."