h a l f b a k e r yClearly this is a metaphor for something.
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Talking about cancer research here is like wearing a suit to a birthday party.. The bigger issue is that I should not be wearing this suit at all. I am not a medical expert and I normally would never dare talk about such an important subject.. However, if I were to tell that my real motive is to be
enlightened on this subject and that I think some of the writers here (at least seem to) have respectible knowledge and opinions on certain subjects which may include what I am writing on in this article, my humble attempt to post an idea on this serious, no-joke topic may be excused.
Having made this explanation, here is the subject of my idea:
As you know, the (most common?) cause of cancer is mutation in the genes associated with cell growth and programmed cell death in the DNA. One of the projected (hoped) cures for this disease is Gene Therapy. This basically involves sending the necessary genes into the cancer cells via gutted virus shells. It is hoped that the carriers of the correcting genes will find the cancer cells, immerse into them, reach the cell nucleus and insert the genes into the correct locations on the DNA. The problem with this method is that the genes may be inserted into "wrong" locations thus causing even more trouble. When you consider hundreds of thousands of virus carriers, there is a good chance this could happen and not only in the cancerous cells. This is the major obstacle in front of Gene Therapy.
My idea, or rather the process that I hope to get lectured on, is first extracting the DNAs of the ill person from his skin cells (since they are plenty), then stabilizing and preserving these complete DNAs for instance by encapsulating them with micelles, and then injecting them with a syringe around the mallcious cells. The first question is: Would these micelles with DNAs find their ways into the malicious cells and plant the DNAs into the nuclei of these cells? If this happens: 1. There would be two copies of the DNA in the nucleus, one with the harmful mutation, the other complete. 2. The complete DNA will contain the necessary genes to regulate the cell growth and death, thus slowing down cancer. 3. When the cell divides, it copies everything in the nucleus, so the good DNA will also be copied. 4. The possibility of insert-mutation (mutation from wrongful insertion of a gene) would be diminished since the complete DNA would not (hopefully) want to insert itself into the other DNA. The above are more questions than projected processes. I have no formal education on the subject but I have the urge to ask an expert, is this a possible cure method, and if it is, is it being tried?
Wikipedia: Gene Therapy
http://en.wikipedia.org/wiki/Gene_therapy
There seems to be different viral methodologies currently under investigation - worth a quick read - as it seems to address some of the issues mentioned here (i.e. does a virus only inject a gene, or does it inject a full-string of DNA, plus consequences relating to viral propagation and self-replication) [zen_tom, May 10 2009]
obligatory
http://www.xkcd.com/938/
xkcd reference [pertinax, Sep 18 2011]
Tumours in the nematode C. elegans
http://stke.science...ct/sci;313/5789/971
[MaxwellBuchanan, Sep 18 2011]
[link]
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Not pretending to know too much here - but as far as your idea goes, it seems half-reasonable to me. However, there are some practical problems that we still need to solve.
1) Viral injection of whole-string DNA - you'd need to individually tailor a virus (vector) so that it injected non-virus (i.e. the patient's) DNA - I'm not sure how effective that is right now (is this how gene therapy currently works?) If a virus injects something else's DNA, is it still a virus? How would you synthesis such a thing? And, if it doesn't make copies of itself (like a normal virus might) then you have to make all of your little nano-DNA-injectors up front, which might be tricky.
2) Cancerous cells aren't just rubbish in terms of irregulated cell division - they're also tend to be misshapen and loosely defined - they may not respond correctly to DNA injection since incorrect DNA isn't their only problem.
3) I'm not sure about how the viral DNA 'occupies' the cell, whether it should be there as duplicate, or replace the old DNA. |
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Hi xkuntay. It's not such a dumb idea, but there are some
flaws. (I should explain - I work on cancer, but not on
gene therapy, so I only half know what I'm talking about.) |
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If I understand, the aim is to get a complete 'normal'
genome into the cancer cells, on the basis that it will be
replicated alongside the cancer genome and will hopefully
correct the defects rather than integrating and
(potentially) causing more harm than good. Yes? |
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If so, then the first problem will be getting the DNA in
there. Handling DNA molecules of that size (on the order
of a hundred megabases for each chromosome) without
breaking them is virtually impossible. Also, no known viral
system would be able to get that much DNA into the cell.
Micelles or some other "synthetic viral shell" might, but it's
pushing it. |
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Second, if you did get a complete "normal" genome in
there, you'd have a tetraploid cell. In most higher
organisms, ploidy changes (extra chromosomes) are bad.
In humans, most ploidy changes are fatal before birth.
Exceptions are triploidy 21 (extra copy of Chr.21) which
leads to Down's syndrome; extra copies of sex
chromosomes (eg, XXX, or XYY) which often have only
minor effects, and a very few others. A fully tetraploid
cell would probably be very bad news. |
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Third, if the cell survived, it would probably divide and
reduce itself back to being diploid; you'd have a random
segregation of the new and old chromosomes to the
daughter cells, probably winding up with a new 'cancer cell'
plus a normal one. Alternatively, the new and old
genomes might recombine, with the real possibility of
creating a really scrambled genome. |
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Fourth, some cancer-driving mutations are recessive (ie,
putting in a 'good' copy of the gene will make up for the
effects of having a 'bad' copy), but others are dominant
(ie, the 'bad' gene is doing something active, and the 'good'
gene won't prevent it from doing so). This is the balance
between oncogenes (dominant genes which drive cancer)
and tumour supressors (recessive genes which, when
faulty, allow the cell to become cancerous). In most
cancers, there is a whole spectrum of mutations (as well as
gene duplications and gene losses) which evolve over
time, and a mature cancer usually has (probably) an array
of both active oncogenes and mutated/lost tumour
supressors. |
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Having said all that, the idea of doing gene therapy by
using a non-integrating vector which replicates alongside
and in step with the native genome is a nice one. I think
it's been considered, though not necessarily in this
context. People have certainly worked on artificial
mammalian chromosomes: these would be sort of mini
versions of normal chromosomes, which could be loaded
up with an "upgrade kit" of genes and transfected into
cells. They would then replicate and segregate alongside
the natural chromosome set. However, at the moment we
still have a lot to learn about chromosomal mechanics and
gene regulation. |
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[+] because it's a sensible idea despite its flaws. |
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Sorry, without a vector of some sort gene therapy is impossible, furthermore for these chromosomes to try to replace the set in the nucleus or replace the function of the nucleus would certainly kill the cell. |
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I love it when HB surprises me, just when I start thinking that the information I can get is no more reliable than youtube news clips. Once again I got more than I expected. Thanks for the lectures. Esp. MB. I knew you were an expert in some field! Not to say your opinions in other fields aren't invaluable. |
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1: very bad news, as [MaxwellBuchanan] explained. |
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3: Your scheme just got the DNA 'into the cell' - this does not necessarily mean into the nucleus - DNA outside the nucleus is terminated with extreme prejudice, because it usually is from outside... viruses developed some nifty strategies to get short fragments integrated (think Jedi-like ' you didn't see this' or simply not inserting DNA but RNA); strategies that rely on throwing large chunks of DNA at cells mostly work in special circumstances/with special cells (e.g ones without nucleus, or temporarily without one) |
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4: inserting code relies on cellular mechanisms that would not respond to a 'whole' chromosome, so no danger there, but see 1. |
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Your background reviews similar scheme: |
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- send cancer-slaying normal gene via special magic key virus transport through the wall of the cancer cell, where normal gene will cause cancer to self destruct. To me this is akin to dropping Secret Agent James Bone onto the roof of the Iranian nuclear facility via special stealth helicopter in the dead of night, where he fools the lock with the cloned finger of Ayatollah Khomeni, enters, and does his secret agent thing with the cloned finger acting as sidekick / straight man. |
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- send all genes indiscriminately via not so special or magic transport (soap bubble) to general vicinity of cancer cell. To me this is akin to carrying the entire population of Trenton, NJ via schoolbuses (but very clean schoolbuses) to the suburbs of Tehran and dropping them off to sort things out. James Bone is among them, along with his extended family, his high school class, his cribbage buddies and everyone else. |
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That is not to say it will not work. Mass action and whatnot, you know. But consider - a cancer cell is already surrounded by copies of normal DNA as normal cells (lymphocytes, stromal cells etc) break down. But maybe there is still not enough. To test this in experimental mice would require spontanous mouse tumors, not grafted human ones. One could riff on the micelle theme and use various liposomes etc as are currently employed to deliver chemotherapy. |
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I liked both scenarios you wrote [bungston], and nice scenario writing too. The first one would definitely win at the box office because it has a superhero and lots of action. The second one would be more like a psychological documentary type movie where the interaction of two cultures is explored, and would be pretty boring to most. And then there could be a third scenario which is totally absurb with sending a bus load of James Bones to the site and have them attend weddings to infuse into the Tehran society. That is mostly for Matrix lovers. Going back to the second scenario, a cultural mixing may actually solve more problems than conflict. Also the whole town being with James can keep an eye on him so that he does not join the enemy forces. But the reality is not a movie after all. It is true what [MB] told, what if they are all corrupted? I don't believe Tehran would turn out to be that evil as to invent a device that turns people into zombies, but the real cancer cells might. And [MB] is right also that it is a good idea to put a non-integrating vector (plasmid) that would act like an additional chromosome so as to at least control the adverse effects. But then he is also right that we are years away from making such a gene. Finally, I totally agree with [MB] that the idea deserves a [+], despite some glitches. Yes, that one is definitely right. |
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A note from the future: After having read a good-deal more on this subject I am still not over this idea. Maybe it is because there hasn't been any James Bond movies for several years. I do miss them. Or maybe I just miss having a bone. Well, hello again bone-shooting croissant-lovers! |
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Here is the updated version of the original: Use adenovirus (see the new terminology?) to deliver the TP53 tumor suppressor gene into all the cells in ones body. That means send an iPad to everyone, yes, but what's wrong with doing some good will? The special iPads will explode if they detect any terrorist activity. Okay, yes there is the danger of all the iPads erronously exploding.. so bone me. I'm back. Half-baked forever. |
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Baked, sorry. Google: Gendicine. |
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I love it how HalfBakery makes me answer my own questions. |
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I wonder how effective Gendicine will be. One of
the problems with cancer is that it's almost never
due to a single mutation. Cells acquire successive
mutations, which allow them to proliferate
moderately, then extensively, then metastically.
Most single-target therapies only give temporary
remission, because a small proportion of the
cancer cells will have a further mutation that lets
them survive and proliferate. It's not so different
from the emergence of antibiotic-resistant
bacteria or antiviral-resistant viruses. |
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If Gendicine kills the cancer cells (by providing p53
protein), then I'd expect it to be as good as other
single-target therapies. However, if it just stops
the cells proliferating, then it will leave a large
population of cells which retain almost a full
house of cancer mutations. Some of them will
inevitably find ways to proliferate. |
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Cancer is a real bastard, because it's an
evolutionary response amongst an ecosytem of
trillions of cells, to escape the factors that
normally limit their proliferation. As such, it's
almost inevitable in any multicellular organism,
and the fact that we don't all develop multiple
cancers is a testimony to the body's defense
mechanisms. Trying to go the last mile and
prevent all cancer is incredibly difficult. |
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It's not possible in organisms with cell constancy, i.e. any of the aschelminthes such as nematodes, and i think also a syncytium would prevent malignancy due to thisses recessive nature, so an aschelminth with syncytial cells, i think, would be unable to acquire cancer. Not very helpful to us deuterostomes of course. However, i have wondered about RSV as a treatment for lung cancer. |
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//It's not possible in organisms with cell constancy//
Good point. |
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//I have wondered about RSV as a treatment for lung
cancer// Well BCG's a treatment for bladder cancer,
so you're nearly there. Oh, and malaria cures
syphilis, which you probably knew already. |
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I suppose something like leprosy or TB might be able to kill tumours but leave the results in situ, which would mean some of their negative effects would continue. |
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But then, [19thly], couldn't you follow up with one-off clean-up surgery? |
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Well, hmm, just wondering what would happen if it
had encroached on the lumen of a blood vessel. I
mean, i don't pursue surgery as a hobby even, so i
don't know about that. Also, angiogenesis -
wondering if it'd bleed like hell. |
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Hey, [19thly], it turns out that you can have tumours
in organisms with cell constancy, like C. elegans
(link). |
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Thanks! I was thinking that if anything was known it
would've been with that. |
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- and that it'd be a germline tumour. Bet there aren't
any in bdelloid rotifers (not that anyone would
know). |
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//surgery as a hobby// The next big thing. |
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Tonsillectomies, vasectomies, trephination and that thing you do for snoring would be good starts. |
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I was thinking of it more as an extension of body
modification (tattoos, piercings, etc) than as
something useful. Trephination, yeah, but the
others are more DIY medicine as John Varley
forsaw it. |
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Surgery appeals to surgeons for a variety of
reasons, but one of them is the adrenaline buzz.
There's lots of people who crave that, but lack the
(among other things) self discipline to become
surgeons. When base diving
and bungee jumping pall,
Mouseposture Industries Stg.
will offer a new form of of medical tourism
travel package, in which the tourist is the
doctor, not the patient. (Several governments
with liberal regulatory
regimes have expressed interest in hosting us.) |
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Trephination, appendectomy, lumbar punctures,
Swan-Ganz catheters, and chest tubes are all
procedures a layman can be taught in a few
weeks, provided you're not too concerned with
complication rates. Marketing is working on an
advertising jingle, but we haven't found a tune yet
for the lyric "mandatory prophylactic endotracheal
intubation." |
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