Please create an account to participate in the Slashdot moderation system

 


Forgot your password?
Close
typodupeerror
×
Biotech Science

Stem Cells Change Man's DNA 171

Posted by Zonk from the oh-man-science-is-weird dept.
An anonymous reader writes "After receiving umbilical cord stem cells to replace bone marrow as treatment for non-Hodgkin's lymphoma, Greg Graves temporarily had three different sets of DNA. Eventually, one of the two sets of cells transplanted into his bone marrow took root, leaving him different DNA in his blood from the rest of his body: 'If you were to do a DNA test of my blood and one from my skin, they'd be different,' Graves said. 'It's a pretty wild thing.'"
This discussion has been archived. No new comments can be posted.

Stem Cells Change Man's DNA More

Stem Cells Change Man's DNA

Comments Filter:

  • Beginning of the end? (Score:4, Interesting)

    by h890231398021 ( 948231 ) on Friday October 05, 2007 @04:23PM (#20873675)
    Perhaps this is the beginning of the end for the use of DNA as "incontrovertable" evidence in criminal cases?

    • Re:Beginning of the end? (Score:5, Informative)

      by debilo ( 612116 ) on Friday October 05, 2007 @04:30PM (#20873785)

      Perhaps this is the beginning of the end for the use of DNA as "incontrovertable" evidence in criminal cases?
      How so? The original DNA isn't gone or hidden. It still can be retrieved, you just need to take several different samples until you find a match.

      • Re: (Score:2)

        by sholden ( 12227 )
        Because the fact that blood at a murder scene matches the doner's DNA, doesn't mean the doner was there - the guy who got the stem cells could have been. So it's not "incontrovertable",not that it ever was anyway...

        • Re:Beginning of the end? (Score:4, Insightful)

          by debilo ( 612116 ) on Friday October 05, 2007 @05:03PM (#20874141)

          Because the fact that blood at a murder scene matches the doner's DNA, doesn't mean the doner was there - the guy who got the stem cells could have been. So it's not "incontrovertable",not that it ever was anyway...
          So the case could be narrowed down to, say, a handful of suspects at best? And that's not taking into account the fact that all of them probably will live in different places, thus either increasing or decreasing their level of suspectedness, and all the other circumstances that would require too great a coincidence to be so indistinguishable that the real culprit couldn't be singled out. Given that, I'd say DNA evidence will stay as foolproof as usual for years to come.

          • Re:Beginning of the end? (Score:5, Insightful)

            by provigilman ( 1044114 ) on Friday October 05, 2007 @05:29PM (#20874369) Homepage Journal
            You're assuming that the police are aware of the multiple DNA profiles. At least in the US we have very strict privacy rules governing medical information...we can't just make someone where a bracelet saying "I have two DNA profiles!!!". Since it's in his medical records it's sealed and someone would either have to remember his name from a news story, or he would need to volunteer the info. (And yes, they can subpoena the medical records, but they would have no cause for doing so unless they already knew)

            So if their DNA evidence came from skin or hair cells he could happily submit to a blood test to confirm that he's not the killer...all without their knowledge. Or vice-versa...they have blood and he says "Yeah, I'll give you a sample, but I don't like needles. Can we just do a cheek swab?"

            Probably what this will lead to, if anything, is duplicate testing and/or testing of the same material as what was found. You find saliva, you test saliva. You find blood, you test blood.

            • And that's not even getting into the idea of people getting stem cells after the crime.

              It's the type of thing I think you'd only see in movies, but imagine a hitman with a private doctor who injects stem cells after every hit... of a hitman who does it without the help of a doctor. The guy could leave different DNA at each crime scene with almost no worries of being linked to each murder.

              Or what if someone inserted the DNA of another person in an attempt to frame the person? Insert DNA, kill someone,

              • Or what if someone inserted the DNA of another person in an attempt to frame the person? Insert DNA, kill someone, scratch yourself with the dead body's nails: instant frame job.
                This is even easier to do without bothering with stem cells.

                The flaw in your plan is that you will be a positive match for the DNA at the crime scene. Bad idea. Better to just plant the DNA evidence.

                • The flaw in your plan is that you will be a positive match for the DNA at the crime scene.

                  ...unless you insert some other DNA, like your original DNA, afterwards. I thought that part was pretty easy to figure out so I didn't bother to explicitly state it.

                  If the fact that it would be skin instead of blood was what was bothering you since the summary talks about how the blood is changed but the skin remains the same, then the guy could cut himself and leave a few drops there. Either way, the point is that

              • It's the type of thing I think you'd only see in movies, but imagine a hitman with a private doctor who injects stem cells after every hit... of a hitman who does it without the help of a doctor. The guy could leave different DNA at each crime scene with almost no worries of being linked to each murder.


                Or, rather, he could leave multiple sets of DNA at each crime scene, and the only common one would be the original one.

            • In the UK, they're apparently making DNA sampling mandatory, and organizing the police databases now to store it.

            • Comment removed (Score:4, Insightful)

              by account_deleted ( 4530225 ) on Saturday October 06, 2007 @12:17AM (#20876897)
              Comment removed based on user account deletion

              • Re: (Score:3, Insightful)

                by Yetihehe ( 971185 )
                If he was in Barcelona on vacations, then he have good alibi. He probably spend some time there, buyed something with his credit card, some people have seen him. He left too many traces of being there, so he have proof of being innocent. Then police would have to PROVE he was not in Barcelona when crime happened.
              • You know, I would hope that a good defense lawyer would stay up on these kinds of developments and would *ask* clients if they've ever donated (or received) stem cells. The dangerous part is when umbilical cells are used and no one ever tells the kid.

            • At least in the US we have very strict privacy rules governing medical information...we can't just make someone where a bracelet saying "I have two DNA profiles!!!". Since it's in his medical records it's sealed and someone would either have to remember his name from a news story, or he would need to volunteer the info. (And yes, they can subpoena the medical records, but they would have no cause for doing so unless they already knew)

              You obviously haven't seen what HIPPA actually does. They don't need a

          • not necessarily true. All that is necessary is reasonable doubt. "Sure, my client's DNA was found at the scene, but knowing as you know do that at least one other person shares that DNA, the choice before you is no choice at all."...

            • Re:Beginning of the end? (Score:4, Funny)

              by StrongAxe ( 713301 ) on Friday October 05, 2007 @08:58PM (#20875933)
              "Sure, my client's DNA was found at the scene, but knowing as you know do that at least one other person shares that DNA, the choice before you is no choice at all."...

              "After all, there is no way of knowing for sure whether this cold-blooded murder was committed by my client, a 50 year old man from Portland, or by a 3-year old toddler from Orlando".

              • "Sure, my client's DNA was found at the scene, but knowing as you know do that at least one other person shares that DNA, the choice before you is no choice at all."...

                "After all, there is no way of knowing for sure whether this cold-blooded murder was committed by my client, a 50 year old man from Portland, or by a 3-year old toddler from Orlando".

                Or the 50 year old man has donated , and his marrow has been used by several recipients in the same geographic area...

                • Or the 50 year old man has donated , and his marrow has been used by several recipients in the same geographic area...

                  Well, the original items were about stem cells from umbilical cords, but I suppose the same issue would also apply to any other bone marrow transplants.

                  • Or the 50 year old man has donated , and his marrow has been used by several recipients in the same geographic area...

                    Well, the original items were about stem cells from umbilical cords, but I suppose the same issue would also apply to any other bone marrow transplants.
                    Hm, forgot about that - it's what happens when I wait a day between replies. Still, it would (theoretically) be the same for other marrow transplants as you say.
          • Everyone has multiple sets of DNA. Some of your mothers stem cells migrate to your body before and during birth. There, they been documented to become immune cells, heart cells in the case of an infant with a weak heart, and other needed parts to help an infant survive. The average person has about 50 million of his mothers cells still alive in his or her body in adulthood. The chances of this affecting a standard DNA sample are infinitesimal, of course. However, 1 in a million adults is a chimera, with

        • Re: (Score:2)

          by Gerzel ( 240421 ) *
          yeah but the practice isn't that widely used yet and there will likely be records of this DNA.

          The DNA testing still narrows it down to a very small set of people.

          • Re: (Score:3, Informative)

            by WhatAmIDoingHere ( 742870 ) *
            The magic words when you have to go to court are as follows:

            Reasonable Doubt.

            • Re: (Score:2)

              by Gerzel ( 240421 ) *
              Yeah, but if DNA can narrow things down to say an handful of people and the prosecution can rule out all of them except one then reasonable doubt is satisfied.

              It can also still help figure out likely suspects AND provide further evidence for the prosecution (or defense).

              Heck Eye-Witness testimony has been proven unreliable by douzens if not hundreds of cases and studies. Yet it is still one of the main sources of evidence in cases today.

              Reasonable Doubt is a reasonably doubtful proposition.
        • Yes, the moral of that story is "if you're going to commit a gruesome crime, donate early, donate often"
    • Considering the level of documentation and rarity of bone marrow transplants... I'm not sure it's really the beginning of the end. Maybe the beginning of one more step in a very limited number of cases...

    • Re: (Score:2, Funny)

      by stonedcat ( 80201 )
      Finally I can murder all those people who made fun of my tinfoil hat!
    • Unlikely. There's plenty of trace evidence he could leave behind that contains his native DNA--hair, skin cells, saliva, semen, probably. So if he was arrested for a crime, it would be a simple enough matter to test a hair sample, or do a cheek swab, which would yield his native DNA. It might create more grounds for reasonable doubt, because the presence of two different sets of DNA might increase the likelihood of contamination during testing. I think it's a stretch, though.
      • "There's plenty of trace evidence he could leave behind that contains his native DNA--hair, skin cells, saliva, semen, probably. So if he was arrested for a crime, it would be a simple enough matter to test a hair sample, or do a cheek swab, which would yield his native DNA. It might create more grounds for reasonable doubt, because the presence of two different sets of DNA might increase the likelihood of contamination during testing. I think it's a stretch, though."

        I was thinking the other day, that if

        • Unlike T.V., in the real world most violent criminals are not terribly bright and are caught through far more stupid actions than those required on CSI.

          If malware writers were really all that good, you'd never know you were infected. Its the same thing.
          • ain't that the truth.

            TV has unfortunately glorified criminals to a certain extent. in the real world they are just stupid thugs without 2 brain cells to rub together, hence why our jails are so full.

            • Just because the stupid criminals are in jail doesn't mean that all criminals are stupid.

              The smart criminals are sitting on the boards of large corporations, or holding office in D.C.
    • If your file can contain your name, along with all aliases that you used,
      and your social security number, along with all the stolen numbers you've used,
      then I'm sure they can find room, for a second set of DNA to be tied to you as well.

    • Crime adapts, science adapts (Score:4, Insightful)

      by hellfire ( 86129 ) <deviladv AT gmail DOT com> on Friday October 05, 2007 @04:58PM (#20874093) Homepage
      First of all, a bone marrow transplant is not currently something Joey Pants can do for you in his brooklyn apartment in 30 minutes just to change your DNA. And the cost and time in the procedure is far greater than simply shaving your body hair, washing down throughly to get dead skin off your body, and wearing thick tight clothes to keep you from shedding any DNA.

      Second, there are plenty of documented cases of someone being a "Chimera" where they contain two sets of DNA in their body. It's usually when an embryo absorbs a twin in the womb. I don't know if there are any true cases out there in the books where a Chimera was tried for a case, but it's known. Science is well aware that DNA is not 100% foolproof, which is why you have probability matches when testing DNA normally. These will simply be bumps in the road and science will adapt. This is nothing new to DNA research. Most likely forensics labs will begin to require taking multiple samples from multiple areas depending on the DNA evidence found. If you left blood at the scene of the crime, why take DNA from your cheek if there's a chance the criminal is a Chimera or a bone marrow transplantee.

      Third, the law will catch up with this. Defense attorneys will use this to create reasonable doubt, and prosecutors will counter to learn about this, while forensics keeps up with the latest scientific trends.

      On the other hand, DNA identification methods for businesses will be completely fucked if someone gets a marrow transplant or is a Chimera and doesn't know it.

      • Most likely forensics labs will begin to require taking multiple samples from multiple areas depending on the DNA evidence found. If you left blood at the scene of the crime, why take DNA from your cheek if there's a chance the criminal is a Chimera or a bone marrow transplantee.

        The problem isn't false negatives for the reason you said. Suppose stem cells are harvested and the same batch is used on a dozen different people. The blood you find at scene doesn't identify a single person. Forensics will label it as a match with 99.99% confidence, however that model is based on conventional ideas of people not sharing the same DNA.

        Though the defense should know enough to bring up this in trial since the defendant should know he's had a marrow transplant.

    • You're missing his point. (Score:4, Insightful)

      by KingSkippus ( 799657 ) * on Friday October 05, 2007 @05:20PM (#20874289) Homepage Journal

      I think the responses so far are missing the OP's point.

      I didn't read his post thinking, "OMG, no more DNA evidence within a few years!" I'm guessing he meant that eventually through the use of various technologies for various reasons, it will be possible for criminals to be genetically altered in such a way that making identifying them using DNA will be difficult. It may be 50 years, 100 years, or 200 years, but as we get better and better at munging up our DNA, it is possible.

      Also, that totally neglects that at some point in the future, when the technology behind this kind of stuff becomes pervasive enough, high tech criminals may deliberately have their DNA altered for the specific purpose of thwarting identification.

    • Re:Beginning of the end? (Score:4, Informative)

      by GooberToo ( 74388 ) on Friday October 05, 2007 @06:18PM (#20874823)
      Don't forget, while very rare, this can and does occur naturally.

      http://en.wikipedia.org/wiki/Chimera_(genetics) [wikipedia.org]
    • A conviction based entirely on DNA evidence would almost certainly be overturned on appeal in most jurisdictions, because DNA evidence can only conclusively prove that the DNA did NOT come from somebody. At best, it can only suggest that it "might" have come from one of many related individuals. Forget CSI: Miami. It doesn't work like that at all. "DNA Evidence" is basically 3 or 4 steps more sophisticated than refuting paternity based on blood type.

      That doesn't mean detectives can't, or don't, rely on DNA

  • That reminds me of someone (Score:4, Funny)

    by LiquidCoooled ( 634315 ) on Friday October 05, 2007 @04:23PM (#20873681) Homepage Journal
    Mary from the trailor park once had 12 different sets of DNA inside her.

    The football team won that night, everybody scored.

  • first man-made chimera? (Score:3, Interesting)

    by pohl ( 872 ) on Friday October 05, 2007 @04:24PM (#20873683) Homepage
    Does this mean Mr. Graves is the world's first man-made chimera [wikipedia.org]?
    • No because we've been doing solid organ transplants for about 40 years. And unless your organ donor is your identical twin, you're going to come out of the operation as a chimera.

    • Re:first man-made chimera? (Score:5, Informative)

      by Ped Xing ( 28860 ) <bruce.callenish@com> on Friday October 05, 2007 @04:42PM (#20873953) Homepage
      No he is not, for several reasons.

      First, he is not the first to have two sets of DNA due to a bone marrow transplant (although he might be one of the first with 3 sets). Anyone who has had an allogeneic (as opposed to autologous) bone marrow transplant like his has that, as do any other transplant recipients.

      In fact, the differences between those DNA is both one of the best things and one of the worst things about alloBMTs to treat blood cancers. The new blood system sets itself up and sees the cancer cells as "foreign" and attacks them, what would be called "rejecting" them in a solid organ transplant. This is called "Graft Versus Leukemic Effect" in leukemia patients, for example. That's the good part. The bad part is that the new blood system looks at the rest of the body and sees it as foreign as well. "All this has to go" is the reaction, also called "Graft Versus Host Effect", or GVHD. That can kill you. Cord blood stem cells make this less likely to happen, because the cord blood cells are not quite sure what the other cells are supposed to look like yet.

      The second reason he is not the first man-made chimera is that he is not a chimera. A chimera is when the second set of DNA comes from another species. That has been done before (organ transplants from pigs, for example), but is not the case in this story.

      The real story here is that he had a stem cell transplant using cord blood from two different donors.
    • If he develops a phage, he'll wonder if he's going to become a Vidiian.

      All I know is "I'm in no mood to donate organs today," as Janeway said.

      http://www.trekmania.net/diplomatic/others.htm [trekmania.net]

      Search for "vidiians" in the site...
  • OK, maybe I've been watching too much CSI these days, but I wonder how this would affect DNA forensics? If a blood sample gives DNA that is identical to my brother or uncle or whatever, and my skin gives "my" DNA, how would the courts handle that?

    It certainly demonstrates a case where DNA evidence does not, in fact, always point to the perpetrator.

    • Re: (Score:2, Redundant)

      by SavedLinuXgeeK ( 769306 )
      There was actually a CSI episode about this. I can't remember the episode, but after a blood transfusion (i think), the man has one set of DNA for his blood, and another for his tissue. This is how we upheld his alibi until a blood DNA test was taken.

    • Re: (Score:2, Informative)

      by mendax ( 114116 )
      You haven't been watching enough Law and Order! There was an episode that dealt with something like this. The man had a bone marrow transfusion. The DNA from his blood had one set of DNA and the rest of his body had another. Thus he could rape with impunity.
  • 1. Commit a crime
    2. Shoot yourself up with stem cells
    3. Don't get thrown in jail because the DNA from the crime scene doesn't match
    4. Waitaminute... Profit belongs in step 1 in this case!

  • Now Britain is going to have to rebuild their DNA database.
  • Cool, but (with all due respect) I'm sure this money could be spent better. On malaria prevention for example.
    • >>> Cool, but (with all due respect) I'm sure this money could be spent better. On malaria prevention for example

      I first read that as "marijuana"
    • I'm sure this money could be spent better. On malaria prevention for example

      Well, yeah. Except, what if they guy who's about to invent a viable preventative for malaria has non-Hodgkins lymphoma?
    • I dunno, I think trying to find a cure for Non-Hodkins Lymphoma is a very good use of research money. Finding a cure for it could also help advance research in solving other cancers.
    • I'm getting pretty sick of this particular line of reasoning. By this logic, we ought to spend 100% of our research efforts on the one problem that is arbitrarily decided to be the worst problem for humanity. Never mind how achievable it is: all other causes are a waste of resources.
  • The story said that the stem cells were from an anonymous boy's birth. Hope somebody has the foresight to tell him and his parents, otherwise, things could get interesting if his DNA is found somewhere else (like a crime scene)
  • ...because all I can think is how well this would work for spies and other undercover types.
    • My wife watches too many spy movies because all I can think is how well this would work for spies and other undercover types.

      Having a wife with a heavy interest in spy movies must make it really difficult for you to keep a girlfriend.

  • Tax Implications (Score:1, Funny)

    by Anonymous Coward
    I think the IRS has ruled this would require filing 3 income tax forms.
  • doesn't a bone marrow transplant do a similar thing? in that case, your bone marrow has different DNA than the rest of your body, or really any transplant would be considered a man-made chimera...

  • And this is news because...??? (Score:5, Informative)

    by the_humeister ( 922869 ) on Friday October 05, 2007 @04:31PM (#20873807)
    We've been doing bone marrow stem-cell transplants for years on people with hematopoietic neoplasms. In fact, we've been doing solid organ transplants for about 40 years. Of course they will have different DNA! In fact, even a normal person has different sets of DNA right now. This is most evident in germ cells, which undergo meiosis, and antibody-producing hematopoietic cells, which change their DNA to be able to make different antibodies to different antigens. So I don't see why this is news.

  • This is nothing new. (Score:5, Informative)

    by wiggles ( 30088 ) on Friday October 05, 2007 @04:33PM (#20873827)
    The procedure is called an Allogenic Stem Cell Transplant. The procedure has been in use for well over a decade, and it replaced the old Bone Marrow Transplant techniques that used to be used for conditions such as leukemia, various cancers, lymphoma, and other immune system disorders.

    The only thing remarkable about this is the fact that the stem cells the man received were from cord blood instead of adult stem cells from a matched donor.

    Wikipedia has an excellent article on the subject: http://en.wikipedia.org/wiki/Stem_cell_transplantation [wikipedia.org]
    The applicable section to this article reads as such:
    "Umbilical cord blood is obtained when a mother donates her infant's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC (hematopoietic stem cells --ed.) than is normally found in adult blood. However, the small quantity of blood obtained from an umbilical cord (typically about 50 mL) makes it more suitable for transplantation into small children than into adults. Newer techniques using ex-vivo expansion of cord blood units or the use of two cord blood units from different donors are being explored to allow cord blood transplants to be used in adults."

    I spent six months in Seattle as a caregiver for a patient undergoing this procedure. The work they do at the Fred Hutchinson Cancer Research Center there is second to none.
  • This is pretty much like a bone marrow transplant. The precursor cells that stay, win pretty much. In this case, your taking those precursor cells

  • 2 sets of DNA? (Score:4, Funny)

    by JayDot ( 920899 ) on Friday October 05, 2007 @04:34PM (#20873849) Journal
    Lawyer: "This is not the DNA you are looking for."

    • Re: (Score:2)

      by SeaFox ( 739806 )
      Lawyer: "You don't need to take another sample..."

      Prosecutor: "We don't need to take another sample."

      Lawyer: "The case is dismissed, you're free to go..."
  • Stem cells change man's DNA? Someone should ask him if he's recently visited a secret underwater city.
  • in that episode, there was a man who cleverly attempted to avoid culpability in a murder because his blood was a different genotype than the rest of him, because he was a chimera [wikipedia.org]. the csi team spends much time in vain trying to pin the murder on the murderer's brothers, because genetic tests indicate he is related to the "real" murderer

    real but extremely rare, it developmentally consists of nonidentical twins in the womb whose embryos fuse very early on, when that is still possible (when they are only a couple of hundred cells, for example)

    then the organism consists of one individual, but one organ system might be a completely different genetic makeup than another organism. so sombody's nervous system could be genetic code A, while his spleen could be genetic code B. chimeras can go through life having no idea what they are, but sometimes, you can see it on their skin (a subtle zebra striping)

  • Change or add? (Score:5, Insightful)

    by pembo13 ( 770295 ) on Friday October 05, 2007 @04:40PM (#20873939) Homepage
    Seems to me that the stem cells added new DNA material, it didn't mutate his existing DNA material.. so why use the word change?

    • Re: (Score:3, Informative)

      by Sique ( 173459 )
      Because the new stemcells replaced the old in the bone marrow. So his blood DNA slowly changed from his own to that of the new stem cells. First there were only blood cells from his DNA, and very few of the new one. Later one the blood cells with his own DNA got replaced by those produced from the new stem cells.
  • Yeah someone stole my identity, they jammed a large metal needle in my arm and stole some bone marrow, four months later i see all these charges on my bank statement saying i spend 30,000 QUID on Mars last tuesday... WTF!!!!

  • 'If you were to do a DNA test of my blood and one from my skin, they'd be different

    Isn't this true of anyone who's had a transfusion?

  • Genetic chimeras and tranplants (Score:5, Informative)

    by UltraOne ( 79272 ) on Friday October 05, 2007 @05:17PM (#20874275) Homepage
    I am a pediatric blood and marrow transplant physician. After every successful bone marrow transplant (BMT), peripheral blood stem cell transplant (PBSCT), or umbilical cord blood transplant (UCBT) in which the donor is not the patient or an identical twin, the recipient becomes genetic chimera. The DNA in cells derived from the bone marrow stem cells is different from the DNA in the rest of the recipient's body.

    As others have pointed out, this isn't anything new. Significant clinical use of BMT dates back to the 1970's. PBSCT and UCBT came into widespread use in the late 1980's and early 1990's.

    My group performed a BMT on a patient with relapsed leukemia a few years ago. The patient unfortunately suffered liver and kidney damage as a result of the BMT. He had a liver transplanted from one donor and later a kidney from another donor. Fortunately, he recovered and has remained leukemia free. He is essentially back to being a normal kid, although he will need to take immunosuppressive mediations to prevent rejection indefinitely. That patient permanently has DNA from 4 different sources (bone marrow, liver, kidney, and his original genotype in all other parts of his body).

  • The really amazing thing (Score:3, Interesting)

    by edwardpickman ( 965122 ) on Friday October 05, 2007 @05:26PM (#20874337)
    What this shows is that a true Chimera is possible mixing human and foreign DNAs. It's amazing that multiple DNA sequences can be supported by the body. Rejection becomes an issue but I'm curious if the body would be more accepting for foreign tissue if it's producing the tissue. The immune system obviously isn't designed to detect foreign DNA but the tissue the DNA is producing is foreign. I'm just curious how far this process can be taken before rejection becomes an problem?
  • So he has 3 different people's DNA in him, big whoop? I wonder how many people's DNA Anna Nichole Smith had in her at any given time.

  • Chiba City Blues (Score:2, Insightful)

    by freshmayka ( 1043432 )
    How long before I can go into a black market clinic and get a DNA swap or rather some DNA camo???

Slashdot Top Deals

In the long run, every program becomes rococco, and then rubble. -- Alan Perlis

Close