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Author
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Topic: Jonathan Wells: Using Intelligent Design Theory to Guide Scientific Research
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Nel
Member
Member # 614
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posted 10. June 2004 14:21
charlie d:
quote:
b) IMO those hypotheses are however, at a scientific level, quite weak. Indeed, I'd say the second one is patently false,
Actually charlie, if centrioles eject a polar ejection force and this causes dna damage, then regardless of whether ultimately, or somewhere in the back or forward chaining of events we find a DNA mutation, this event is quite independant of DNA mutation.
That is all Wells is saying about the second hypothesis. Wells never said "DNA-don't-do-squat", as you stated earlier. Why would you say that? Indeed Wells himself states:
quote:
TOPS does not preclude a role for DNA mutations
So I have no idea what paper charlie is replying to. Also, the causes of cancer have by no means been illuminated with any degree of certainty. Take an example I gave a while back as an analogy, Rb null fibroblasts suggest that inactivation of RB is not sufficient for tumorigenesis since the cell stays normal.
charlie wrote:
quote:
Everyone here agrees that anyone can derive inspiration for science wherever they want - that doesn't make the source of inspiration valid, or useful, by default. YECs have pioneered the use of patently false premises to conduct what would look superficially as valid science, reaching wrong conclusions in the process.
ID has already been involved in premises and predictions that turn out be correct. I would like charlie, and those in this thread that agree that this is scientific research to just say it. Whats so hard about it?
A lot of the ID critics, are asking why Wells hasn't participated in a while. I don't really know why he'd come back to be quite honest. Some are still harping about irrelevant topics, some just keep asking the same question over and over again, and some think that we are 100% certain about every aspect of cancer.
[ 10. June 2004, 14:30: Message edited by: Nelson-Alonso ]
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Evan
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Member # 164
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posted 10. June 2004 16:15
I am certain that there is no one here who believes, has said, or even implied that "we are 100% certain about every aspect of cancer."
Also, the reason some of the same questions have been asked is because they haven't been addressed, and yet they have been brought up by new participants in the thread.
[ 10. June 2004, 16:16: Message edited by: Evan ]
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charlie d.
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Member # 159
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posted 10. June 2004 17:12
Nelson:
I never said we are "100% sure of every aspect of cancer" - did I? On the other hand, we are fairly sure (as sure as we can scientifically be) that specific changes in a cell's DNA (whatever their source: cosmic radiation, burned barbecue or centriole malfunction) are ultimately responsible (and necessary) for the alteration of cellular growth and survival mechanism during neoplastic transformation. Whether that is or not covered under the statements: quote:
TOPS assumes ... that various implications of ID are true. These include... that cancer originates in higher structural features of the cell rather than in its DNA
or quote:
TOPS explictly rejects several implications of Darwinian evolution. These include... that cancer is a genetic disease.
I'll leave to you to rationalize.
As to whether Rb is specifically involved in cancer (although it escapes me why you brought that up):
a) since the predominant model is, and has been for a couple of decades, that cancer is due to the accumulation of multiple genetic "hits", no one would expect a single hit to cause a neoplastic phenotype in 100% of the targets. That Rb deficiency is nnot sufficient to transform all its targets is therefore not only not surprising, it's predicted by the model;
b) Regardless, Rb deficient fibroblasts, although not transformed, certainly show cell cycle alterations of the same type as those observed in transformed cells;
c) making general conclusions about whether alterations of a single gene are involved or not in tumorigenesis just by looking at fibroblasts is a rather simplistic extrapolation anyhow;
d) essentially complete cancer penetrance in Rb heterozygous knock-out mice and retinoblastoma patients make as strong a case as one can make for the role of Rb as a tumor suppressor (indeed, Rb mutations defined the concept of tumor suppressors). There really isn't much space to argue there.
Finally, I am getting out of this thread since the tone is again degenerating. If the mods are willing to enforce their own proposed standards, all the better.
[ 10. June 2004, 17:15: Message edited by: charlie d. ]
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Rex Kerr
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Member # 632
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posted 11. June 2004 03:39
I, for one, hope that Wells takes the objections raised in this thread and uses them both to improve his presentation of the link between Intelligent Design and the formulation of his hypotheses (clearly, a source of confusion), and to improve the detail, rigor, and biological plausibility of his model (or reject the model if this cannot be done).
As an author, that's what comments are good for--so you can improve your own work. I don't think there's anything devious about that!
(In fact, I wish that more of the objections that concern me were addressed in ID books.)
[ 11. June 2004, 03:41: Message edited by: Rex Kerr ]
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Josh
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Member # 405
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posted 11. June 2004 09:56
I have several issues with this hypothesis as outlined.
Wells cited Khodjakov, A., et al. As a reference indicating that cells
without centrioles lack polar ejection forces, however if one reads the
article, chromosomal movements change during mitosis:
"Our observations reveal that Haemanthus spindles possess stage-specific
non-kinetochore-based chromatin transport systems that are neither
present during astral mitosis nor previously demonstrated for any other
animal spindle. Unlike during astral mitosis, we show clearly for the
first time that a poleward force is exerted along the entire length of
Haemanthus chromosomes during spindle formation and chromosome
congression. Then, at the onset of anaphase, this force disappears and
is replaced by an opposite force that is similar to the polar ejection
force seen in animal somatic cells."
So, these cells without centrioles display chromosome movements
consistent with polar ejection force. This seems particularly damaging
to the hypothesis.
Wells also states "The force has been attributed to microtubule
elongation and/or microtubule-associated motor proteins, but neither of
these explanations fits all the facts (Wells, 2004)." The reference is
to something unpublished, and needs more support.
>From the Slieder and Salmon review:
"Finally, when cells containing monopolar spindles are treated with
drugs (e.g.,
nocodazole or taxol) or temperature shifts that affect microtubule
turnover, chromosome oscillations quickly cease and the chromosomes
assume a new position relative to the pole characteristic of the drug
treatment (4, 11). When chromosome arms in nocodazole-or taxol-treated
monopolar spindles are severed from the kinetochore region by a laser,
they do not move further from the pole (4). These findings demonstrate
that the polar ejection forces generated in association with each aster
and half-spindle are mediated by microtubules, and they further suggest
that this force is dependent on the dynamically unstable nature of
microtubule growth."
Taxol stabilizes microtubules, thus allowing for any vortexing mechanism
to remain. However, chromosomes cease movement under these conditions.
If taxol prevents turbine centriole movement, this would not be a
problem, however microtubule instability and motor action appear to
account for all chromosome movements.
Also, from the Haemathus study;
Does the poleward force acting on chromosome arms in forming Haemanthus
spindles also act on other components within the spindle? According to
Bajer and Mol~-Bajer (1956), some small "particles" in Haemanthus
metaphase spindles do move poleward with the speed of anaphase
chromosomes, but others oscillate irregularly or move to the spindle
equator at the same time. Nicklas and Koch (1972) similarly found that
0.7-3.0-p,m diam lipid droplets and mitochondria commonly exhibited
poleward motions with the speed of anaphase chromosomes when
micromanipulated into metaphase spindles of grasshopper spermatocytes.
However, they also emphasized that such particles underwent radial
motion out of the spindle as often as poleward motion, and the behavior
of ACFs was never addressed. Thus, although limited, the current data
suggest that when positioned in the spindle, membrane-bound particles
undergo stochastic, bidirectional, "saltatory" motions along Mts that
differ from the exclusively smooth and poleward motion of ACFs.
It seems that these particles would be especially susceptible to such
polar ejection forces described by Wells since they are not known to be
specifically attached to microtubules and would thus move based only
upon other non-microtubule attachment/motor based forces such as a PEF
hypothesized by Wells. In sum, I simply don't recognize why we need
such a hypothesis since microtubule instability and motor movements seem
sufficient to account for the behavior of chromosomes and cellular
particles during mitosis.
Other general comments. My impression of centriole duplication is one
of exciting biological interest, see for example Kirkham, M., et. al,
Cell 112: 575-587 (Cell is a top notch publication.) The reason for
lack of understanding of centrosome biology is not, IMO, lack of
interest as it was discovered over 100 years ago, but due to the
untenable nature of studying it. Recent genetic and proteomic tools
have begun to dissect the problem of centrosome biology (such as
Andersen, JS et al., Nature. 2003 Dec 4;426(6966):570-4.) The
centrosome is one of the black boxes of biology and is growing in both
interest and intense of study. In regards to centriole malfunction and
cancer, my impression was that defective centrioles mostly regard
over-duplications or premature separation of paired centrioles in cancer
cells thus leading to multipolar spindles which segregate the genome in
toward multiple poles thus inducing aneuploidy. I have not previously
heard of a widely appreciated role of enlarged centrosomes causing
defects. Also, chromosome instability revolves around the spindle
assembly checkpoint which monitors the attachement of kinetochores to
the poles. Unattached kinetochores that persist during chromosome
segregation will lead to aneuploidy, and these are the most recognized
mechanisms for chromosome instability (as I understand it.) Genetic
lesions are normally associated with chemical/irradiation treatment,
indeed some of the referenced papers use irradiation to produce
chromosomal fragments without kinetochores to analyze their movement
during mitosis.
[ 14. June 2004, 19:53: Message edited by: Josh ]
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Nel
Member
Member # 614
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posted 11. June 2004 13:07
charlie:
quote:
I never said we are "100% sure of every aspect of cancer" - did I? On the other hand, we are fairly sure (as sure as we can scientifically be) that specific changes in a cell's DNA (whatever their source: cosmic radiation, burned barbecue or centriole malfunction) are ultimately responsible (and necessary) for the alteration of cellular growth and survival mechanism during neoplastic transformation.
I disagree. For example, one paper, Oncogene (2004) 23, 2016–2027, states:
quote:
Mutations in certain genes involved in the spindle checkpoint have been identified in a variety of human cancers (Cahill et al., 1998). Although these mutations have not been found very frequently and a causal connection between these mutations and CIN has not been established unequivocally, the understanding of the spindle checkpoint might provide valuable insights into CIN and facilitate the design of novel therapeutic approaches to treat cancer.
While many genetic changes may be key to complete transformation, I think that there are also other possibilities for their origination that have not been ruled out. For example, epigenetic (not directly involving mutations, amplification, etc in DNA) changes that may operate early in tumorigenesis. Some of these involve methylation of DNA resulting in silencing of genes, others, however are structural, like Wells suggests in his hypothesis. Clearly, centrosome abnormalities drive chromosomal instability in cancer.
charlie:
quote:
a) since the predominant model is, and has been for a couple of decades, that cancer is due to the accumulation of multiple genetic "hits", no one would expect a single hit to cause a neoplastic phenotype in 100% of the targets. That Rb deficiency is nnot sufficient to transform all its targets is therefore not only not surprising, it's predicted by the model;
I doubt that anyone predicted this type of data. A lot of this stuff is just hit and miss. For example, in the thread where I brought this up, you were arguing that these type of diseases were monogenic.
But more specifically, I would say that the normal behavior of Rb-null cells in vivo was a
surprise. Because the gene is so commonly affected in human cancer, it would be expected that it would have a greater affect on its own.
charlie:
quote:
b) Regardless, Rb deficient fibroblasts, although not transformed, certainly show cell cycle alterations of the same type as those observed in transformed cells;
Although I wouldn't be surprised, since Rb may play a role in cell cycle control. However, I am not quite sure this is true, since the reason why Rb-null fibroblasts behave reasonably normally is likely because there are redundant regulators, such as p105 and p130 - relatives of Rb -- that are able to help regulate proliferation in the absence of Rb. But like I said, I wouldn't be surprised if it is. Most likely Rb-null cells can escape from quiescence and senescence, which are also properties of transformed cells.
charlie:
quote:
c) making general conclusions about whether alterations of a single gene are involved or not in tumorigenesis just by looking at fibroblasts is a rather simplistic extrapolation anyhow;
No, one should never make general conclusions. One should tread carefully on a case by case basis, especially in a field that is suposed to be tentative. But then, thats the entire point I've been trying to make.
charlie:
quote:
d) essentially complete cancer penetrance in Rb heterozygous knock-out mice and retinoblastoma patients make as strong a case as one can make for the role of Rb as a tumor suppressor (indeed, Rb mutations defined the concept of tumor suppressors). There really isn't much space to argue there.
I never claimed that Rb wasn't.
[ 13. June 2004, 12:38: Message edited by: Nelson-Alonso ]
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