-Caveat Lector- Is this what the Ets are doing I wonder? N We have the power http://www.newscientist.com/ns/19991023/newsstory6.html A safer way of altering genes will make engineering humans more tempting than ever MICE ENGINEERED TO CARRY an extra artificial chromosome have successfully passed it to their offspring. Although the Canadian company responsible has no intention of repeating the experiments in people, its work shows that human germline gene therapy--making genetic changes that will be inherited by future generations--is becoming a practical possibility. Chromos Molecular Systems of Burnaby, British Columbia, reported the breakthrough this week in London at a conference on biotechnology. "It's the first time an artificial chromosome has ever been shown to be inherited in any mammal," says Eileen Utterson, vice-president of corporate development. Chromos plans to use the technology to create herds of genetically modified animals whose milk will contain pharmaceuticals. Geneticists have been creating transgenic animals for years by injecting genes into a newly fertilised embryo. When this method works, every cell in the animal that develops from the embryo will contain the added genes, including its sperm and eggs. This means that the genes will be inherited by the transgenic animals' offspring. It's a haphazard process, however. Often the gene doesn't get incorporated into the embryo's genome. And when it is, the gene splices itself at random into one of the animal's chromosomes, where it may not work as normal or, worse still, can disrupt other genes--potentially causing developmental abnormalities. While occasional "mistakes" are tolerated in animal experiments, the danger of causing congenital defects is one of the reasons why germline gene therapy for people has remained taboo. So instead of trying to correct genetic defects such as the mutations that cause cystic fibrosis at the start of life--by adding genes to embryos created by IVF--gene therapists treat people with genetic disorders by adding therapeutic genes to specific tissues in the hope that they will be taken up by enough cells to correct the defect. While this ensures that sperm and egg cells do not become contaminated by the added genes, it isn't very efficient. As a result, many gene therapy trials have had only limited success. However, if genes could be ferried into embryos in an artificial chromosome that would safely be inherited without interfering with the rest of the genome, germline gene therapy might not be so risky. Chromos's experiments with mice suggest that this should be possible. "Because the artificial chromosome is separate, it doesn't interfere with the cell's own genetic machinery," says Utterson. In London this week, Chromos presented preliminary results of experiments with mice given an artificial chromosome. By taking cell samples and exposing them to fluorescent dyes that bind to different parts of the chromosome, Chromos's scientists were able to discover which animals had accepted the chromosome. When the mice carrying the extra chromosome were crossed with normal mice, it was inherited in exactly the same way as the animals' natural chromosomes. Chromos is also working on human artificial chromosomes for use in conventional, non-germline gene therapy. Artificial chromosomes will have an advantage here as well, because they can carry much more DNA than is possible with existing methods, which use viruses or loops of bacterial DNA known as plasmids. But the company says it won't let its technology be used for human germline engineering. "We are in control of the technology, and we don't want to engage in germline gene therapy," stresses Utterson. However, many groups worldwide are also striving to create artificial human chromosomes. And some geneticists are talking openly of one day using such chromosomes for germline gene therapy (New Scientist, 3 October 1998, p 24). "This is obviously going to open up the debate again in the field of germline gene therapy," says Norman Nevin of Belfast City Hospital, who chairs Britain's Gene Therapy Advisory Committee. However, scientists advising the world's governments remain cautious. Claudia Mickleson of the Massachusetts Institute of Technology, who chairs the US National Institutes of Health's Recombinant DNA Advisory Committee, says that her committee wouldn't approve a germline trial without extensive preclinical information on safety. And given concerns about the technology being used to create "designer babies", Mickleson also says trials would not proceed without "intense discussion" with the public . (see Editorial) How to make an artificial chromosome CHROMOS's scientists start with natural chromosomes that possess one pair of full-length arms, and another pair of stubby arms containing no working genes. Using DNA-manufacturing enzymes, the researchers duplicate these stubby arms and extend them with inert "satellite DNA". The full-length arms drop off, leaving an artificial chromosome containing only the elements it needs to survive and copy itself. (see diagram). These elements include telomeres, repeating sequences of DNA that cap the tips of the chromosomes and stop them merging with other chromosomes. In the middle is a centromere, the "kink" in a chromosome that hooks it to the protein guide wires along which it moves when a cell divides. Finally, the researchers weave genes of interest, as well as the switches needed to control them, into the chromosome's backbone of satellite DNA. Chromos has also invented a technique for injecting the chromosomes into cells or embryos with a fine needle. This took two years to perfect because the chromosomes are so much larger than the small quantities of DNA usually inserted through microinjection. Andy Coghlan >From New Scientist, 23 October 1999 DECLARATION & DISCLAIMER ========== CTRL is a discussion and informational exchange list. Proselyzting propagandic screeds are not allowed. Substance—not soapboxing! These are sordid matters and 'conspiracy theory', with its many half-truths, misdirections and outright frauds is used politically by different groups with major and minor effects spread throughout the spectrum of time and thought. That being said, CTRL gives no endorsement to the validity of posts, and always suggests to readers; be wary of what you read. CTRL gives no credeence to Holocaust denial and nazi's need not apply. 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