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Science

Goodbye, Dolly 409

goombah99 writes "Dolly, the famous cloned sheep has been put to death after being diagnosed with a progressive lung disease, according to many reports. This follows on earlier reports that she was prematurely aging, including developing arthritis. While one should be cautious about drawing conclusions from a single data point, its interesting to speculate." Here is a link to her birthplace courtesy of Captain Large Face
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Goodbye, Dolly

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  • by tealover ( 187148 ) on Friday February 14, 2003 @04:10PM (#5304693)
    Hello Lamb Chops !!!

    This is the best thing about cloning. An endless supply of lamb chops !!!

  • by Anonvmous Coward ( 589068 ) on Friday February 14, 2003 @04:11PM (#5304707)
    "While one should be cautious about drawing conclusions from a single data point, its interesting to speculate."

    It's obviously a sign from above...
  • by Cipster ( 623378 ) on Friday February 14, 2003 @04:12PM (#5304711)
    There is nothing sadder for a parent than having to burry their clone....
    Somehow that just did not sound right.
  • First clone (Score:2, Interesting)

    Ya know, it was a good run for the first complex clone (mammal). I bet eventually they get the kinks worked out and cloned everything will be available. But for now, it's like the old addage: "in order to make an omlette, you have to break a few eggs."
    • Re:First clone (Score:5, Informative)

      by interiot ( 50685 ) on Friday February 14, 2003 @04:17PM (#5304787) Homepage
      The main suspected "kink" are the telomeres, and if we do discover it's a kink, it may be a difficult one to work around. Here's [www.exn.ca] a good article on telomeres and telomerase.
    • Re:First clone (Score:5, Insightful)

      by spiro_killglance ( 121572 ) on Friday February 14, 2003 @04:37PM (#5304993) Homepage
      Its more important than that, that fact clones aren't medically identical or as fit as the
      orignal, tells us, that there is something we
      don't know about genetics. Whatever it is, it
      can cause premature aging and auto-immune disease,
      that may well mean, that whatever we learn about
      why clone are unfit, can produce cure for auto-immune diseases and maybe slow down aging.

      Perphap the key to clones failure is methylization, the genes in cells can be selectly
      switched on and off by attacting methyl group
      to potions of the DNA, how this works, is controlled, and how/if its passed on, is very
      important unknown of cell biology. In the same
      way over half the DNA is a cell, is made up of
      intron sequence that don't code for proteins or gene, however intron a preversed across millions
      of years of evolution, human share many of the
      same introns as mice. That means introns have to
      be doing something important, but unknown. We've
      much yet to learn about cellular biology and cloning as much to teach us.
  • by dalassa ( 204012 ) on Friday February 14, 2003 @04:13PM (#5304730) Journal
    I wouldn't rush to conclusion with this one case but it does remind me of one basic biology tenet I learned. Cells will divide a specific number of times and then stop dividing. Cells taken from an older individual will divide less than cells taken from an infant. So until we learn to increase divisions won't animals cloned from adults have issues with cell division and this is perhaps the cause of the premature ageing seen in cloned animals.
    • If this is the case (and it should be seen in other clones (cats, rats, etc...) then we need to be focusing more attention on how to permit cell reproduction many more times. This would have a more direct affect on aging and cancer (as many cancer cells are basically immortal and can replicate forever).
      • How it works (Score:5, Informative)

        by Raul654 ( 453029 ) on Friday February 14, 2003 @04:26PM (#5304885) Homepage
        The basic answer to your question is already know. The mechanics of it are simple -- at the end of the DNA strand in each nucleus is a length of DNA that codes for nothing, called a telomere. With each division, the telomere gets cut back. Eventually, the cell divides one last time and the telomere isn't long enough, so the cut goes right into part of the DNA that codes for something, thus causing an error catastrophe ultimately resulting in death.

        But take hope. In the 1980's, while studying cancer cells (in fish, I think), researchers found this chemical called telemorase, which rebuilds the telomeres. [For which one of the more recent nobel prizes was awarded] Ever since, researchers have been working feverishly on telemorase treatments, which we should start seeing in the next decade or two.
        • Re:How it works (Score:3, Interesting)

          by qbwiz ( 87077 )
          Unfortunately, it's no coincidence that telomerase is found in cancer cells. It's likely that if you had telomerase in your cells, your body would turn into a big cancerous mass within a few years, because the cells would always continue to divide, and wouldn't stop like they should. There's always hope that we'll be able to get around that (slight;) problem.
        • Re:How it works (Score:5, Interesting)

          by Milo Fungus ( 232863 ) on Friday February 14, 2003 @05:22PM (#5305383)

          ...chemical called telemorase...

          Telomerase isn't just any chemical - it's a protein. Protein therapy is not easy stuff.

          First of all, injested proteins are degraded in the digestive tract - virtually none of it is absorbed in active form. That's like trying to get useful cow protein into your bloodstream by eating beef. It won't work. The digestive system chews up proteins into small peptides or individual amino acids.

          Even if you do get active protein into your bloodstream, it still usually has a very short half-life in the body. The body's native proteins do as well. That makes it easier to regulate them. Proteins are degraded in a certain amount of time and re-synthesized if more are needed.

          The best way to administer protein treatments is through gene therapy - but there are several problems here as well. First is the problem of getting the gene into the genome. That's difficult to do with high success. Then you have to have an appropriate promoter sequence. These are regions of DNA that tell the cellular machinery to actually synthesize the gene that you've inserted. Promoter sequences need to be subject to appropriate regulation by cellular signals. If the expression levels aren't right, you could have some pretty serious problems.

          Yeah, it's a mess. But we're making slow progress at figuring things out one piece at a time. Dolly was a big step.

          My first experience with computer programming was on an IBM PC-Junior with GW-Basic. I remember reading the source of Basic games that I would play to figure out how they worked. I would tweak things here and there and then run the file to see how it changed the game. Biologists are basically doing the same thing. There is not documentation. There is no RTM. There is only tweak and observe.

        • Re:How it works (Score:3, Informative)

          by nfk ( 570056 )
          Wow, hang on. Telomeres are what you said, but telomerase is an enzyme whose function is to maintain telomere length. Its activity is normal and, to an extent, necessary in stem, germ line and other cells. It allows division to occur without shortening the telomeres but, as development continues, cells are only supposed to have a limited number of divisions. Telomerase becomes inactive, telomeres get shorter with every division and when they reach a threshold size, the cell stops dividing or dies. In cancer cells, telomerase is activated, thus bypassing the mechanism that leads to senescence and originating immortal cell lines. The goal of those treatments you mentioned is probably to shut off or alter in some way the production of telomerase.
    • From what I understand after my few biology classes and limited reading on genetics, this is caused by telomeres. Telomeres are useless bits of DNA that are stuck on the ends of each DNA strand, and every time the strand is replicated, a little piece of this telomere is broken off. The more that's broken off, the older the strand.

      It should be noted that a cloned animal/human would in effect start off with DNA that's had the same amount of telomere breakoff as the adult or child the DNA was taken from. Grab DNA from a 40-year-old person, and you have a clone that starts off with 40 years less to live.

      However, as I am not involved in any actual cloning (I'm a CS student... hence the reason I come here), I don't know what(if any) steps scientists take in cloning to deal with this. We've known about telomeres for quite some time, we've extended the life of some life forms (tape worms and mice) many times past normal through manipulation of these telomeres, and we've found genes/hormones that reduce the effects of aging.

      Perhaps this premature death is a result of ignoring this problem? Perhaps it's something else entirely. I can only regurgitate what I've read thus far.
      • Do I just have a huge gap in knowledge here, but isn't reproduction the merging of seperate halves of DNA? How would it get a new set of telomore? Are the egg and sperm created with it preadded? Which side would decide the total amount? Furthermore, to make a single body isn't the DNA already duplicated millions of times? How many extra bits are there?

        Though if this is correct, and to throw out a tangent, would it then be possible to compare the length at natural death now with specimens from long ago to see if our life span really is increasing? This is mainly a hypothetical question; other than mummies there probably aren't many samples of DNA from long enough ago that would make for a good study.
      • Perhaps this premature death is a result of ignoring this problem [shortening of telomers with age]? Perhaps it's something else entirely. I can only regurgitate what I've read thus far.

        There was a report some time back that Dolly was showing shortened telomeres, consistent with not having the length of the telomeres restored to the normal for an egg/sperm combination during the cloning process. There was speculation at the time that this would lead to premature aging.

        The enzyme telomerease, which rebuilds telomeres, is well-known at this point. Adding a little to the egg in the cloning process will solve this issue. If that is the only difference between a cloned individual and the original (other than the mitochondrial inheritance), cloning of medically "normal" "younger twins" - animal or human - will soon be a done deal.

        Dolly's breakthrough was showing that the differentiation "switches" in the original cell could be "reset" to the embryonic default settings. This implies that cell differentiation (at least in the type of cell used for the DNA source) was not an irreversible editing of the DNA (like that in the differentiation of the immune system), involving loss of information necessary for other tissues, but was something else that is easily reset by the enzyme systems of the egg.

        Dolly's offspring will show if the normal reproductive system will restore the telomeres to normal length even in the eggs of a cloned mother with reduced telomeres (or oversized ones from intervention during cloning). This seems likely.

        Meanwhile, the ability to clone whole organisms with shortened telomeres (but otherwise-normal telomere-related systems) should quickly lead to research that sorts the various old-age-related medical problems into those that result from telomere shortening and those from other causes.
  • by intermodal ( 534361 ) on Friday February 14, 2003 @04:13PM (#5304732) Homepage Journal
    was this aging relative ot the age of the donor sheep? perhaps the clone picks up where the cell left off. I have after all heard that dna starts to fray at the ends after enough dividing (i am not a biologist, so i might be wrong)
  • I brought you into this world, I can take you out and make another one that looks just like you.

    Will this be casue for a Scottish National Day of Mourning?

    • "Will this be casue for a Scottish National Day of Mourning?"

      Isn't every day spent eating Haggis a cause for a National Day of Mourning? Just because today the sheep's stomach happens to be form a clone, should it really be any different?

  • by Twirlip of the Mists ( 615030 ) <twirlipofthemists@yahoo.com> on Friday February 14, 2003 @04:14PM (#5304744)
    This follows on earlier reports that she was prematurely aging, including developing arthritis.

    The light that burns twice as bright burns half as long. And you have burned so very, very brightly, Roy-- um, I mean Dolly.
  • One of the scientists stated that the cloning process used to make Dolly might have been inefficient, and that sheep usually live 10-12 years.

    I hope that the people opposed to cloing dont take her untimely death as a reason to stop further research into this field.

    I for one cannot wait to see spaarti cylinders everywhere. (That was a Star Wars joke, FYI...)
  • by CommieLib ( 468883 ) on Friday February 14, 2003 @04:15PM (#5304755) Homepage
    "We had to put her to sleep," they said sheepishly. "She was in shear agony. There was mutton we could do about it."
  • At least (Score:2, Funny)

    by dubiousmike ( 558126 )
    I'll have my inflatable sheep to remember her by...

  • While one should be cautious about drawing conclusions...

    It's a little late to be cautious.

  • While one should be cautious about drawing conclusions from a single data point, its interesting to speculate.

    Recall, however, that the success rate to at least produce Dolly was only around 1 in 200. This is still an early-stage technology, and there will be many more obstacles along the way. That, in my mind, is the major justification for a ban on human cloning at this time...

  • by sboyko ( 537649 )
    It wasn't cloning that got her lungs - it was secondary cigarette smoke from the black sheep of the family.
  • by Doctor Beavis ( 571080 ) on Friday February 14, 2003 @04:17PM (#5304778)
    Although the shortening of her telomeres is well-publicized, it very well may have had nothing to do with the death. A somewhat more detailed story can be found here [reuters.com] [Reuters].
    • More than one data point. Dolly is actually the second cloned sheep to die in a week. Matilda, a cloned sheep born in the year 2000 in Australia died last week. Autopsy results were inconclusive. Matilda's passing [yahoo.com].

    • But the problem is that they have no idea what really did her in and what they did wrong. I really love the nuts that thinks the first time they try to clone a human it will work perfectly. Ha. About as likely as ... fill the blank... But seriously, it was a stroke of genious to think that when we can't figure out how protiens fold and what most of the junk inside cells do, that we could move some DNA around in a rather clumsy way and voila have a perfect clone. Next thing they are going to start talking about error free coding... yada yada yada. Dolly is dead and we don't have a clue and won't for a long long time. And when we do successful cloning we won't have a clue about what we did right, what we did wrong or what the difference is between the two.
  • by TWX_the_Linux_Zealot ( 227666 ) on Friday February 14, 2003 @04:20PM (#5304821) Journal
    Remember, Blade Runner (and Do Androids Dream of Electric Sheep?) had such first...

    In fact, isn't it a bit ironic that a sheep is prematurely aging, versus the mechanical fake sheep (and title) in Philip K. Dick's novel?
  • by circletimessquare ( 444983 ) <circletimessquareNO@SPAMgmail.com> on Friday February 14, 2003 @04:21PM (#5304828) Homepage Journal
    this is good...

    i was all set to make believe i saw ufos so i could join up with the raelians. i don't know how long i could have maintained that lie. but since these are the only folks who will cut off the head of my clone and put my brain in his shell, what can a craven mortal do?

    since it looks like all this cloning stuff won't give me unlimited life yet, now i don't have to maintain the charade.

    i'm going to tell those raelians the truth and give them a piece of my mind!

    oh wait, er...
  • by akiaki007 ( 148804 ) <aa316NO@SPAMnyu.edu> on Friday February 14, 2003 @04:22PM (#5304832)
    is 10-14 years. Dolly lived to be 6+.

    Not to draw any conclusions, but I don't think too many people will be taken back by this, unless of course you were one of the people who helped create Dolly and actually thought that she was completely normal.

    Despite the fact I am against cloning, I would like to find out more results to this. What would the avg. lifespan be if there were 100 Dolly's (and I suppose 1,000,000 failed attempts as well). It might be interesting to know, though somewhat dusgusting to get to.

    End result - this won't bode too well for cloning simply because Dolly developed this disease only half-way through her life. What will be much more interesting is to follow her child - I believe she gave birth to a female sheep in 1998 - 2 years after Dolly's birth.
    • It might be interesting to know, though somewhat dusgusting to get to.

      Not to be trollish, but why? It's a frickin' sheep, for God's sake. It's not like it wasn't going to eaten or put into dog food at the end anyway, right? Same for a million of them (or their genetic material which could easily be thrown down a drain or allowed to decompose). It might be a huge amount of effort (with 1,000,000 trials), but how one gets from that to disgusting, I don't see. Don't tell me - you didn't grow up in a farming community, huh?

  • There was a man shipwrecked on an island with only his dog to keep him company. After weeks and weeks of being alone, he finally found some sheep grazing in a field. The man had once heard that if you fsck a sheep it sorta feels like a woman. Being desperate, he started towards the herd. His dog immediate runs up, barks, and they all run away. The man scolds the dog, and decides to try again the following day. Again, he finds the sheep, and as he approaches, his dog again barks and chases them all away. This time the man is really pissed, and kicks the stupid dog. The following day the man decides to try again, only this time when he gets to the field, there is a beautiful woman surrounded by a pack of wolves. Thinking quickly, the man grabs his dog by the tail and uses it as a club to beat off the wolves. Grateful, the woman offers to do anything he wants. Elated, the man replies "here, hold my dog"!

    =)

    (I have no idea where this joke came from)
  • Bladerunner (Score:3, Insightful)

    by theCat ( 36907 ) on Friday February 14, 2003 @04:24PM (#5304863) Journal
    Many of you will recall that replicants had 4 years to live. It was built-in and they knew it and hated it.

    I hate it when life immitates art, because some of our art is strange and the really good stuff is damn creepy. Dolly was cloned from a mature sheep, and the theory goes that she basically picked up where her...parent?...left off on the aging timeline. But that's not going to stop many wanna-be immortalists. So when some 80 y.o. geezer elects to have himself cloned the "new" baby will have the genetic signiture of an octagenarian, and probably 10 years to live a life of pain and senility.

    This stuff sucks, people. You don't have to be a flaiming Bible thumper or a neoLuddite to be freaking out about Dolly. I think about how giddy everyone is about their personal fsckig immortality and my skin crawls.

    Eat well, exercise, love someone with all your heart, have a good time. Have lots of great sex and leave a few really smart, well-adjusted children. Then go off and FUCKING DIE! OK? Just die and leave this earth to the next generation, born in the usual way with their own chance to live their own life their way, as nature had intended. Please!
  • Damn... (Score:3, Funny)

    by ktakki ( 64573 ) on Friday February 14, 2003 @04:25PM (#5304870) Homepage Journal
    Now my Valentine's Day plans are all shot to hell.

    k.
  • I am a sad clone.
    Why do people hate me so?
    I am human too.

    The sheep was useful,
    but reporters stopped coming.
    Then we got hungry.

    Millions of dollars
    of research grants is a lot
    to spend for haggis.

    The girl is not her
    mom, The scientists, just baked
    Scientologists.
  • by Anonymous Coward
    I just heard some sad news on talk radio - the cutting edge cloned mammal Dolly was found dead in her Maine home this morning. There weren't any details. I'm sure we'll all miss her, even if you weren't a fan of her creators' work there's no denying her contribution to popular culture. Truly an American icon.
  • ... that she existed at all. Without this research no one would have known that this was an issue with cloning. Imagine how much more we as humans would know if *all* research was unfettered by government regulation and/or religious superstition.
  • by PizzaFace ( 593587 ) on Friday February 14, 2003 @04:40PM (#5305027)
    If mature animals have "old" DNA, how do their offspring get "young" DNA?

    I think of DNA aging as a process of random decay over time, but somehow my old DNA and my wife's old DNA can produce a baby with young DNA.

    Does the combination of DNA during sexual reproduction clean up the strands from the parents? Or is something going on in their gonads to clean up their old DNA before packing it into gametes?

    There's a biological process here that I haven't heard anyone describe, or even identify. And yes, I want to patent it.
    • Found here [vicnet.net.au]:

      Telomeres are found on the ends of chromosomes. They are a small sequence of DNA repeated many times. They act as protective "caps" and help to prevent chromosomal instability and damage. However the telomeres gradually shorten over the lifetime of the organism because they are not fully copied during cell division. The exception to this are germ-line cells, where telomeres are maintained so that full-length telomeres are passed on to the next generation.

      Pretty interesting.... I didn't know that myself. Anyhow, don't thank me, thank google.

    • Your wife's old DNA does not produce a baby.

      DNA from her eggs makes a baby.

      All of the cells that develop into eggs are created in the
      fetus, and then wait until puberty to develop into eggs.

    • by Some Dumbass... ( 192298 ) on Friday February 14, 2003 @06:06PM (#5305737)
      There's a biological process here that I haven't heard anyone describe, or even identify. And yes, I want to patent it.

      Patent a biological process involved in sexual reproduction?

      Can you say "prior art"? :) :) :) :) :)

  • This may just be my opinion, but instead of wasting time cloning animals, scientists should be figuring out how to transplant brains into robotic bodies. Being able to live forever as a cyborg is far more important to me then having a clone of myself which will just grow old and pathetic.
  • I'd wager most /.ers don't even get that joke.
  • ...They remembered to make backup-copies.
  • Incept Date (Score:3, Interesting)

    by rwiedower ( 572254 ) on Friday February 14, 2003 @05:04PM (#5305216) Homepage
    Wait a minute...I'm an identical twin who is 24. Does this mean that I should look forward to Carousel soon? Or that I should start harvesting my clone's organ farm...?
  • by NigelJohnstone ( 242811 ) on Friday February 14, 2003 @05:34PM (#5305492)
    What about the risk with Genetic Engineering?

    A genetic engineer takes a gene sequence, millions of bases long, changes a few and observes the results.

    Imagine a hacker, taking a 10MB binary, disembling it by hand, randomly tinkering with a few bytes here and there, then looking for effects when they run it. Would you consider that app bug free?

    if anything the hacker has an advantage, we can't write a DNA person, but we can write a machine code program.

    Dolly's problems appeared in the first generation clone. But if no problems were observed after only a few generations of breeding from dolly it would have been declared safe.

    In nature though, the changes are slow and small and the testing much much longer, and even then whole species become extinct when some weakness become apparent.

    I reckon GE is a much bigger risk than cloning.

    • by the gnat ( 153162 ) on Friday February 14, 2003 @11:23PM (#5307137)
      Wrong for two reasons:

      1. Genetic engineering is not "random". A better comparison would be a hacker taking 10MB of source code to some random program and adding an email client. (hey, like Emacs!)

      2. The genetic code can handle quite a bit of "random" mutation. There are cases where it is extremely sensitive to mutation, such as sickle-cell leukemia (single poylmorphisim that causes hemoglobin to form chains), but there are "silent" mutations and even amino acid mutations that will have no effect.
  • by lingqi ( 577227 ) on Friday February 14, 2003 @07:55PM (#5306409) Journal
    It's actually a pretty important question, if you think about it, not even on the "at least give the sheep what it might want" sort of way. few examples:

    * does cloned animals retain "normal" sexual apetite? (i.e. would a cloned panda be more, or possibly even less willing to fuck than the one's we've got right now?)

    * If dolly does suffer from premature aging, would her offspring suffer the same thing? how would the offspring from a cloned animal be compared to an offspring of the source animal? (with the same "father," let's say)
  • by Greyfox ( 87712 ) on Friday February 14, 2003 @08:18PM (#5306527) Homepage Journal
    It wasn't that Dolly was a clone. Dolly was kept indoors with a bunch of other sheep (some clones, some not) and this virus was spreading in the whole population. It doesn't sound like the disease was directly related to her being a clone.
  • oops (Score:3, Funny)

    by Sludge ( 1234 ) <slashdot.tossed@org> on Friday February 14, 2003 @11:22PM (#5307133) Homepage
    Looks like someone left a bug in Dolly's overloaded operator=

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