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Tom Anderson - 06:18pm Mar 2, 1998 ET (#3700 of 3701)

Curiosity was framed, ignorance killed the cat

No, actually it was not an error in my math. The first time I took account of probability, the second time I did not take account of probability until the paragraph after the equations. So they both work.

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Tom Anderson - 06:22pm Mar 2, 1998 ET (#3701 of 3701)

Curiosity was framed, ignorance killed the cat

BTW, Noel, I hope you like the translation into geek-speak ;o)

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Frank Joyce - 08:06pm Mar 2, 1998 ET (#3702 of 3712)

Tom:

you state " If the fetal cells grow by 150% each growth period (your number), and then have a 50% chance of being removed"

Each individual cell that would be in the population would be have a 50 percent chance of being removed. Thus if you start with one and end with 3-4 during the period they were first brought up then that's like flipping a coin 3-4 times to get the possibility of them being removed. They only have a 50% chance as you say if they exist in the media as a clump. Which they would not after being treated with trypsin and shaken. Then each round you have decreasing odds that they are removed as more and more fetal cells appear. Thus even if only two cells exist after first being brought up there is a 75% chance that at least one would remain.

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Tom Anderson - 08:48pm Mar 2, 1998 ET (#3703 of 3712)

Curiosity was framed, ignorance killed the cat

Frank,

They only have a 50% chance as you say if they exist in the media as a clump. Which they would not after being treated with trypsin and shaken. Then each round you have decreasing odds that they are removed as more and more fetal cells appear.

You're getting closer anyway. If there is one cell in the beginning, then there are two, maybe three, after one growth period. The mean probability would eliminate one, maybe two, after the first division. However, the deviation from this probability cannot exceed one cell without eliminating all of them. Probability would have it that the actual ratio of cells selected out would certainly deviate from the mean. Also, you are still negleting the extremely small possibility that there is even one cell in the beginning at all.

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Frank Joyce - 12:46pm Mar 3, 1998 ET (#3704 of 3712)

Tom:

Lets not forget your model for thier existance was severely flawd as well. You tried to state 75 trillion cell types in the body as part of yoru estimate. with those odds it would have been impossible to even get and adult fiberblast.

So again the possibility of it being selected out if one indeed existed. would give us 2 -3 after the first round since they have the higher rate. and again they will be expected to to exist separately and not act as one clump of cells which would be eliminated with a 50% chance. remember if there are only two in the beginning there would be a 50% chance of either surviving + a 25% chance of both. thus 75% after the first round. Thats assuming the lower numer of only two clees existing before the split. If there are 3 before the fisrt split then there is a 12.5% chance that all three are eliminated. Anyway the odds increase with each round of replication that they will persist in the media. Put that into perspecitve with your orifgional statement that only 1% would be fetal cells. a number you've had to find new ways of changing. Even by using 75trillion in your estimates.

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Tom Anderson - 02:36pm Mar 3, 1998 ET (#3705 of 3712)

Curiosity was framed, ignorance killed the cat

Frank,

You tried to state 75 trillion cell types in the body as part of yoru estimate.

I never said anything about how many cell "types" there are, I only said that there are 75 trillion cells in the human body (ref. Encyclopaedia Britannica). Given that 200 thousand cells are fetal cells, that makes for a very, very small proportion of fetal cells, and an extremely small (almost no) chance of randomly selecting a fetal cell. Compounded with that is the liklihood that, even if one were selected, it would almost certainly be eliminated during culturing.

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Frank Joyce - 04:18pm Mar 3, 1998 ET (#3706 of 3712)

Tom:

And again, We are not taking an entire human body and putting it in a culture flask are we? we are cutting tissue from an udder. Thus you can't use an estimate like 75 trillion in your estimate. No matter where you cite it from we are stull using the excised udder tissue.

Thus if one cell cell exists then at the rate of division you would expect that by the 2nd or third splitting two divisions would have taken place and 4 cells exits before you split. From that point on, before you the 3rd split each time, there would be two doublings, one stating immediately after the preceding split and one completing before the third split. All it takes is one cell to last 2-3 splittings and you would then have 4 in the population and only 1/16th the chance of removing all of them. And so on and so on before every 3rd split thereafter.

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Frank Joyce - 04:19pm Mar 3, 1998 ET (#3707 of 3712)

BTW lets not forget that in origionally bringing the cells up from tissue Wilmut did make a selection for Fiberblasts. This would be both fetal and adult since fetal fiberblasts are beleived to be the cells in question.

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Noel Yap - 04:34pm Mar 3, 1998 ET (#3708 of 3712)

Tom Anderson: The number of fetal cells after n divisions: for (var j=0; j<n; j++) if = [(if(1+rf))(0.5)]; The number of adult cells after n divisions: for (var j=0; j<n; j++) ia = [(ia(1+ra))(0.5)];

You're still assuming that half of the sample is discarded at each division. Aside from that, the above model is an oversimplification of the model I posted (ie it still uses discrete time.)

BTW, is the above some pseudo-language you use, or is it some other language -- the last time I saw "var" was in Pascal and I don't think it was used in this manner. Might it be Mathematica? Also, most veteran C++ programmers code: for(j = 0; j != n; ++j) If you're wondering why, consider the implications of STL, operator overloading, and consistency of code.

Tom Anderson: in reality there is a fifty percent chance that the fetal cell population will be eliminated in any of the early experiments since there is only one or two cells in the culture at the time. So for the first fifty to a hundred divisions, any fetal cells in the culture are likely to be selected out.

This is true. That's why I qualified my model with the assumption of uniform distribution.

Tom Anderson: These equations also assume that there is at least one fetal cell to begin with, which itself is a most improbable occurrance.

This is true, too, but the model can be easily changed to take into account probabilities rather than overall populations. But I see that you've already done this in your following post. Here's what I come up with (using continuous time):

Let ft = iferft be the number of fetal cells at time t</ b>.

Let at = ia

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Noel Yap - 04:37pm Mar 3, 1998 ET (#3709 of 3712)

This is true, too, but the model can be easily changed to take into account probabilities rather than overall populations. But I see that you've already done this in your following post. Here's what I come up with (using continuous time):

Let ft = iferft be the number of fetal cells at time t.

Let at = iaerat be the number of adult cells at time t.

The probability of choosing a fetal cell at time t would then be:

ft/(ft+at)

It should be noted that the variables if and ia could be taken as the initial probabilities instead of the initial numbers.

Tom Anderson: BTW, Noel, I hope you like the translation into geek-speak ;o)

I'm so fluent in certain dialects that I didn't even notice it ;)

Frank Joyce: They only have a 50% chance as you say if they exist in the media as a clump. Which they would not after being treated with trypsin and shaken.

This fulfills one of my major assumptions.

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Noel Yap - 05:17pm Mar 3, 1998 ET (#3710 of 3712)

Tom Anderson: Compounded with that is the liklihood that, even if one were selected, it would almost certainly be eliminated during culturing.

I disagree. If there were one cell before the separation, it would have a 50% chance of being eliminated (50% is not almost certainly.) Add to this that the biologist chooses when to perform the separation. This means there is probably more than one fetal cell before the separation.

Let's say there was one fetal cell in the original culture and it divides roughly twice every three days. If the biologist decides to discard half the cells at the sixth day, chances are there would still be eight fetal cells left. Frank, please plug in the proper numbers into my model (unless you find something wrong with it.)

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Dawn Willis - 05:33pm Mar 3, 1998 ET (#3711 of 3712)

Just dropping in between business trips, and don't have time to go through hundreds of posts, but I'll make a few comments, biased though I am (according to Tom!) As I understand it, Wilmut wasn't expecting success, and therefore didn't bother to consider that a pregnant ewe was not the best choice, particularly since he couldn't document the DNA of the ewe, the ram that impregnated her, or the fetus she was carrying. Others have tried to clone sheep and cows from adult cells but none of the embryos have survived to birth. A team at U Mass and another at a Wisconsin biotech firm, Infigen, say they have calves in utero that were cloned from adult cells, but neither group is confident enough that these calves will make it to reveal the tentative due dates. Something, perhaps poor placental development, seeems to cause problems around the time of birth. Even so, most scientists agree that if Dolly isn't the first clone of an adult cell, getting one is just a matter of time and doing enough transfers.

By the way, Tom, I recently learned that the detection of fetal cells in maternal blood is under development as a way to identify genetic abnormalities in the fetus.

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Dawn Willis - 05:56pm Mar 3, 1998 ET (#3712 of 3712)

Dolly's DNA is under analysis by an independent lab to determine if it has the characteristics of "old" DNA. I don't understand why the cloning researchers aren't using pluripotent stem cells for nuclear transfer, except that they are very rare (but present in bone marrow and less so in blood)and are difficult, but not impossible, to culture. There are also unipotent and oligopotent stem cells in the epidermis and the lining of the GI tract that might clone better than a terminally differentiated cell. Indeed, Dolly may have originated from such--but so what? Still an adult cell.

Regarding old DNA, in the March 2 issue of "The Scientist" Grifo and Zhang at NYU say they have shown that removing the nucleus from an older woman's egg before meiosis and inserting it into a younger woman's enucleated egg does not affect the reconstructed egg's ability to mature in vitro. They hypothesize that it is the egg cytoplasm, not the nucleus, that is responsible for the effects of maternal aging, such as in Down's syndrome. And Jacques Cohen of Cornell reported a procedure in which he transferred the husband's sperm along with a small amount of cytoplasm from healthy donor eggs to the eggs of an infertile woman and got a healthy baby girl.

New Post:

>Dawn Willis: Dolly's DNA is under analysis by an independent lab to determine if it has the characteristics of "old" DNA.

If Campbell and Wilmut are doing this, I would suspect it is because they have detected such aging abnormalties. You can bet they have performed the tests, themselves. If they detected aging abnormalities, the independent lab should also.

>Dawn Willis: I don't understand why the cloning researchers aren't using pluripotent stem cells for nuclear transfer, except that they are very rare (but present in bone marrow and less so in blood)and are difficult, but not impossible, to culture. There are also unipotent and oligopotent stem cells in the epidermis and the lining of the GI tract that might clone better than a terminally differentiated cell. Indeed, Dolly may have originated from such--but so what? Still an adult cell.

Carl, I'm not sure, but I think that I may have had my face slapped. Dawn's reference to "terminally differentiated cell" may mean that your "degree of differentiation" idea is correct. But I guess we'll have to wait until the "biased" expert gets back to find out. I won't give in until I am told point blank by Dawn that I am wrong. (And even then I might not completely change my mind, although I will, of course, shut up about it:-)

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Carl Nicolai - 01:29am Mar 4, 1998 ET (#3714 of 3726)

Located in Taipei Taiwan

Ref. Cliff Beall #3713

The problem with the concept of differentiated cell is that no one can tell just what it means. Terminally differentiated cell is just another varient of the basic problem.

Unless there is a locking mechanism, weither involving "jumbing geans" or some irriversable change to the necular genetic structure, which I doubt, or a loss of genetic information the only thing I can think that terminally differentiated means is that you can not make a zygote type cell, or any other type of cell, with it. This begs the question.

There are chemical bonds that can not be reversed because information is lost. The easiest to understand is the change that happens when you scramble an ordanary egg. The heat causes bonds to be broken and reformed in a new tightly woven 3 dimentional structure. Information is destroyed and can not be reinserted because of the new structural density.

Now *that* is a terminally differented cell.

There have to be some operating mechanisms that can be measured for "differentiated cell" to have any concrete meaning. Several have been hinted at, but nothing really hangs together on a conceptual level.

BTW someone pointed out that by some definitions a zygote is extremely differentiated.

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Tom Anderson - 07:13am Mar 4, 1998 ET (#3715 of 3726)

Curiosity was framed, ignorance killed the cat

Frank,

We are not taking an entire human body and putting it in a culture flask are we? we are cutting tissue from an udder. Thus you can't use an estimate like 75 trillion in your estimate.

With a complete lack of understanding of simple math, I don't see how you can possibly have passed highschool. In order to get the ratio of fetal cells to adult cells, you take the total number of them in circulation in the entire body and divide by the total number of cells in the entire body. This gives the ratio of fetal cells to adult cells anywhere in the body, including the udder! Also keep in mind that 75 trillion is a modest estimate since that is for a human body and sheep are generally more massive than humans.

Thus if one cell cell exists then at the rate of division you would expect that by the 2nd or third splitting two divisions would have taken place and 4 cells exits before you split. From that point on, before you the 3rd split each time, there would be two doublings, one stating immediately after the preceding split and one completing before the third split. All it takes is one cell to last 2-3 splittings and you would then have 4 in the population and only 1/16th the chance of removing all of them. And so on and so on before every 3rd split thereafter.

This is absolutely wrong. After the first split, if probability follows exactly, then you would have 1.25 times what you started with, and since you cannot have 0.25 cells, you would have only one cell again. After several divisions, a small deviation from the mean would certainly eliminate this one.

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Tom Anderson - 07:14am Mar 4, 1998 ET (#3716 of 3726)

Curiosity was framed, ignorance killed the cat

in origionally bringing the cells up from tissue Wilmut did make a selection for Fiberblasts. This would be both fetal and adult since fetal fiberblasts are beleived to be the cells in question.

First, if this statement were true, it would be irrelevant. But, what I find so fascinating is that a PhD candidate in biology could make so many biological mistakes in one sentence. For instance, the first couple of times I thought you just made a typo, but apparently you actually believe there is something called a "fiberblast". Surely you could not misspell "fibroblast". Then, the claim that Wilmut selected for fibroblasts is rediculous; he could certainly tell between a fibroblast, which is very distinctive, and an epithelial cell. Also, fibroblasts are not the most likely cells coming from the placenta. These statements of yours, in addition to your total lack of mathmatical knowledge, are leading me to believe that you are not who you say you are. What did you say the name of your school was?

Noel,

You're still assuming that half of the sample is discarded at each division. Aside from that, the above model is an oversimplification of the model I posted (ie it still uses discrete time.)

That's because half of the sample is discarded at each division. And continuous time is not necessary since we can simply say that it grows X percent during each discrete growth period.

BTW, is the above some pseudo-language you use, or is it some other language

It's pseudo code, but it would probably be how I would write it in JavaScript. In fact, the comparator operators are that way because that is best for JS. Though Java and C++ wouldn't be that far off that statement, but Pascal is a completely different syntax. Well, I guess it is apparent what I've been programming in lately.

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Tom Anderson - 07:22am Mar 4, 1998 ET (#3717 of 3725)

Curiosity was framed, ignorance killed the cat

It should be noted that the variables if and ia could be taken as the initial probabilities instead of the initial numbers.

True, but that does not account for the fact that cells are quite discrete. Probabilities of less than 0.5 are basically equivalent to zero, especially after several divisions at that probability.

If there were one cell before the separation, it would have a 50% chance of being eliminated (50% is not almost certainly.) Add to this that the biologist chooses when to perform the separation. This means there is probably more than one fetal cell before the separation.

Fifty percent is the mean; a deviation is almost certain. A deviation of only one or two cells would eliminate all fetal cells. Compound this over several separations with the same chance of such a deviation.

If the biologist decides to discard half the cells at the sixth day...

The biologist wants to keep roughly the same volume of cells, so he will divide it in half every time the population doubles.

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Tom Anderson - 07:29am Mar 4, 1998 ET (#3718 of 3725)

Curiosity was framed, ignorance killed the cat

Dawn,

By the way, Tom, I recently learned that the detection of fetal cells in maternal blood is under development as a way to identify genetic abnormalities in the fetus.

I understand now where the "fetal" cells are coming from; sorry, but you did not explain it well the first time. They are not coming from the developing fetus itself, but from the placenta -- that part of the placenta in contact with the maternal blood sinuses. This being the case, it severely limits the types of fetal cells that could be in the blood, and all of which are just as differentiated as any adult cell.

Dolly's DNA is under analysis by an independent lab to determine if it has the characteristics of "old" DNA.

If it is determined to be "old" then that is evidence one way, but if it is not, it cannot be determined whether or not the DNA was "fixed" by the oocyte.

better than a terminally differentiated cell

This was the point of the experiment -- to determine if there is such thing as a "terminally differentiated cell", or rather to disprove it.

They hypothesize that it is the egg cytoplasm, not the nucleus, that is responsible for the effects of maternal aging, such as in Down's syndrome.

I believe that Down's Syndrome results from nondysjunction during meiosis II.

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Frank Joyce - 02:56pm Mar 4, 1998 ET (#3719 of 3725)

Tom:

Firsxt off the bat, I think everyone would agree that I have mellowed out and avoided making personal attacks. Why Haven't you?

Second when you take the entire blood stram of the animal you forget that Red blood cells have no nucleus. You would only be concerned wioth white blood cells which grow differently thatn fiberblasts.

The difference in the way cells grow, allows wilmut to make a selection, which he does talk about, Fiberblast grow as a cell layer at the bottom of the culture flask. all other blood cells would not form a layer that is interconected with extra cellular matrix and thus can be eliminated lightly swirling the media to suspend them and pouring them off the layer of fiberblasts.

Finally We don't know the area of bottom of the original culture flask and how many doublings it would be expected to take before they reach the concentration wilmut chose as a maximal concentration to maintain. thus many doublings may have occured before the cells were split for the first time. Your model only works well when you start with one cell. There may have been many cells before the first split.

Again as you origionally stated there would be a 90% chance of adult cells in medium 7% chance of stem cells and 1% chance of fetal cells. I assume you mean the other 2% consists of other types of cells.

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Frank Joyce - 02:59pm Mar 4, 1998 ET (#3720 of 3725)

BTW there is another error inyour math.

You assume 50% split twice a day, If the expected rate for adult cells is 15-16 hrs then over time you would not have any cells left. If you did they would all be fetal since expected split time is 9-11 hrs. Just under the 12 hr split time. thus if you want to fix your problem then either change the split time to 16 hrs or adjust the pecentage you remove each split.

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Noel Yap - 03:42pm Mar 4, 1998 ET (#3721 of 3725)

Tom Anderson: In order to get the ratio of fetal cells to adult cells, you take the total number of them in circulation in the entire body and divide by the total number of cells in the entire body.

When taking samples from the udder, you would figure out how many are fetal and how many are adult. I think Frank was trying to point out that your sample population is incorrect.

Tom Anderson: This gives the ratio of fetal cells to adult cells anywhere in the body, including the udder!

You're assuming a uniform distribution. The concentration of fetal cells within the udder can be (and I would guess would be) higher than in the rest of the organism. One would have to verify the concentrations through experiment.

Tom Anderson: Also keep in mind that 75 trillion is a modest estimate since that is for a human body and sheep are generally more massive than humans.

You're assuming all cells have equal mass.

Tom Anderson: After the first split, if probability follows exactly, then you would have 1.25 times what you started with, and since you cannot have 0.25 cells, you would have only one cell again.

This is incorrect. We're dealing with probabilities, not absolute numbers. The expected number of fetal cells at day one (notice I didn't say "after the first split") is not necessarily integral just like the expected number of children per family in the US is 2.3 (?).

Again, Tom, this is much easier to see if, instead of quantizing time by when the cells split (and this itself is fuzzy), use continuous time and the rate (per day) of the splitting.

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Noel Yap - 03:47pm Mar 4, 1998 ET (#3722 of 3725)

Tom Anderson: After several divisions, a small deviation from the mean would certainly eliminate this one.

This follows your incorrect assumptions.

Tom Anderson: These statements of yours, in addition to your total lack of mathmatical knowledge, are leading me to believe that you are not who you say you are.

I agree.

Tom Anderson: That's because half of the sample is discarded at each division.

But, again, there is no exact time for division. Also, you would still have to count the probabilities without conditions. IOW, you're biasing your numbers by calculating the probabilities given that the first division would select out the fetal cell. If you make assumptions such as these, you wouldn't make such a good financial analyst.

Tom Anderson: And continuous time is not necessary since we can simply say that it grows X percent during each discrete growth period.

Continuous time is necessary 'cos the cells divide many times and, more importantly, that we are dealing with different growth rates (ie a different ranges of growth rates for fetal and adult cells.) Anyway, your model is exactly the same as my discrete model except that you account for the halving of the culture (which I claim doesn't affect the expected numbers) and it's less efficient and more error prone (but we're not dealing with high precision numbers anyway.)

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Noel Yap - 03:49pm Mar 4, 1998 ET (#3723 of 3725)

Tom Anderson: Though Java and C++ wouldn't be that far off that statement,

Although one could code that way in C++, an experienced C++ programmer wouldn't. There's just some styles that are specific to a language. This particular one has it's roots in STL's iterator interfaces, operator overloading's inefficiencies, and consistency of code. The reason I bring this up is 'cos (please don't take this personally) you seem to profess that books perfectly reflect practice. This is not true (ie no books talk about the implications of operator overloading). OTOH, I would say that if you dug deep into professional journals, they would more precisely reflect the details of reality, (ie the above C++ stuff has been written about in only a few articles that I've seen in C++ Report.)

Tom Anderson: True, but that does not account for the fact that cells are quite discrete. Probabilities of less than 0.5 are basically equivalent to zero, especially after several divisions at that probability.

But, in the end, it is the probabilities that we're trying to calculate. One must carry out the entire calculation first when trying to figure out the expected number of fetal cells. Another way of doing the calculation (that's less perfect) is through Monte Carlo simulation. Either way, one doesn't go on with the calculations with the assumption that the (possible) initial fetal cell is selected out early. One might as well say that 1/1000000 is "close enough to zero." Again, using assumptions like these too early in the calculations is very crude and would lead to large losses in the markets.

Tom Anderson: The biologist wants to keep roughly the same volume of cells, so he will divide it in half every time the population doubles.

Why not keep the other half? Why discard it? Why do they

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Noel Yap - 03:51pm Mar 4, 1998 ET (#3724 of 3725)

Why do they try to keep the original number of cells to begin with?

One way to end this debate is to try Monte Carlo simulation. When doing so, make sure that the division rates are different between fetal and adult cells. We could make it simpler by assuming there exists one fetal cell to begin with and accounting for this possibility afterward.

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Noel Yap - 04:54pm Mar 4, 1998 ET (#3725 of 3725)

Frank Joyce: Finally We don't know the area of bottom of the original culture flask and how many doublings it would be expected to take before they reach the concentration wilmut chose as a maximal concentration to maintain.

Can you supply guestimates?

Frank Joyce: There may have been many cells before the first split.

Given what's been posted, I would have to agree with Tom that this is a highly unlikely event.

Frank Joyce: Again as you origionally stated there would be a 90% chance of adult cells in medium 7% chance of stem cells and 1% chance of fetal cells. I assume you mean the other 2% consists of other types of cells.

Are these likely percentages? Can we use them in the model?

Frank Joyce: [Tom] assume[s] 50% split twice a day,

This has already been pointed out. Are you lagging a day or so? Tom and I are in EST (-5 GMT).

You still haven't commented on my model. If you are indeed a PhD candidate, I would expect that you understand the math for growth rates. Are you going to have an open discussion or are you just going to argue with Tom? Please respond.

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Frank Joyce - 07:19pm Mar 4, 1998 ET (#3724 of 3744)

Noel:

Sorry just getting caught up from the weekend. I need to go back and review the model you've stated.

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Frank Joyce - 07:27pm Mar 4, 1998 ET (#3725 of 3744)

Tom:

Let me remind you tath Wilmut in teh title of his paper states that he has done beoth Fetal and ADULT cells. The argument that placenta is just as differentiated doesn't hold because it would be considered fetal. He would not be able to call it and adult cell in his title.

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Noel Yap - 07:34pm Mar 4, 1998 ET (#3726 of 3744)

Frank Joyce: Sorry just getting caught up from the weekend. I need to go back and review the model you've stated.

No problem. One note, though, the model must take into account what Tom has been trying to get across -- that once there are zero fetal cells in the culture, there can be no fetal cells henceforth. Gimme a couple of weeks and I'll have something.

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Frank Joyce - 07:47pm Mar 4, 1998 ET (#3727 of 3744)

Tom and Noel:

Split times are an important consideration but only in the earliest part of establishing a culture. This provides a model much like Random Genetic Drift. Thus when there are fewer intitial cells It is far more difficult to overcome being selected out. The only thing favoring not being selected out is the rate. If the doubling times overcome this. Thats why it more important to think in terms of how the splits are occurring and the number of fetal cells before each split.

Another consideration is that spliting will maintain the adult cells at a constant max point and min point. YOu don't want the cells to exceed the max pt because they begin to grow differently and many enter G zero as the begin to overcrowd. So the model must assume that the adult cells will stay within a Constant range.

Ultimately if you have only one cell to start with, the odds would faavor removal assuming slow rate of growth. But in this case the growth rate is different enough to give good odds for it being maintained especially if you start with more then one Before the first split

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Frank Joyce - 07:55pm Mar 4, 1998 ET (#3728 of 3744)

BTW to all:

I was actually trying to avoid the word random since that seems to be an entire topic in here

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Frank Joyce - 10:22pm Mar 4, 1998 ET (#3729 of 3744)

I think in a good model we can't assume that mitosis goes back to time 0 after the split. I think we all agree that would be impossible. I think that is what noel and I have both pointed out in our statements and we should look for ways that will allow us to encompass both.

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Tom Anderson - 12:31am Mar 5, 1998 ET (#3730 of 3744)

Curiosity was framed, ignorance killed the cat

Frank,

I think everyone would agree that I have mellowed out and avoided making personal attacks. Why Haven't you?

Maybe its aftershocks from your initial round of intense battering, or maybe it is because there are serious flaws in your reasoning and your credentials are coming into question, especially considering you so strongly pushed them on us to begin with. But that's not really relevant to the argument, so I'll try to restrain myself henceforth.

Second when you take the entire blood stram of the animal you forget that Red blood cells have no nucleus. You would only be concerned wioth white blood cells which grow differently thatn fiberblasts.

No, you wouldn't be concerned at all with any blood cells. Who ever said anything about this? You're just throwing out more red herrings again.

The difference in the way cells grow, allows wilmut to make a selection, which he does talk about, Fiberblast grow as a cell layer at the bottom of the culture flask.

He did NOT select for fibroblasts (note the correct spelling)... he selected for epithelium.

Your model only works well when you start with one cell. There may have been many cells before the first split.

No, you are wrong; there is a very slim possibility of even one, certainly not more than one.

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Tom Anderson - 12:32am Mar 5, 1998 ET (#3731 of 3744)

Curiosity was framed, ignorance killed the cat

Again as you origionally stated there would be a... 1% chance of fetal cells.

That was my original statement, however Dawn pointed out scientific literature which gives numbers which would make it very much less than 1%. It is more along the lines of 2.67E-7 percent.

there is another error inyour math... You assume 50% split twice a day

That is not an error -- it has no effect at all on the result. My results come from the assumption that it is split 50% every time the culture grows 100%. The twice a day figure was just used as an estimation in saying 730 splits due to twice a day for one year, but replace that number with 600 or 800 and it still does not amount to much of a difference.

Noel,

I think Frank was trying to point out that your sample population is incorrect.

But it is not.

You're assuming a uniform distribution. The concentration of fetal cells within the udder can be (and I would guess would be) higher than in the rest of the organism.

Yes, I am assuming uniform distribution because there is no reason for dead or dying fetal placenta cells to accumulate in the udder. If there would be an accumulation anywhere, it would be in the kidneys, liver, bladder, or intestine -- in preparation for elimination.

You're assuming all cells have equal mass.

Yes. Cells cannot surpass a certain volume without severely weakening the membrane and the cell as a whole. For this reason, cells of a certain type do not vary much in relative mass, even between fairly distant species. Also, when you are talking about the difference between a 120 lb woman and a 300 lb ewe, there are certainly more cells in the latter.

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Tom Anderson - 12:34am Mar 5, 1998 ET (#3732 of 3744)

Curiosity was framed, ignorance killed the cat

We're dealing with probabilities, not absolute numbers.

Yes, we are dealing with probabilities, but there will not be any fetal cell growth after the second split if they were all eliminated by the first one, even though probability would show an indiscrete value.

Again, Tom, this is much easier to see if, instead of quantizing time by when the cells split (and this itself is fuzzy), use continuous time and the rate (per day) of the splitting.

But continuous time would lead to errors because the experiment actually was done in discrete amounts of growth per division rather than slowly dividing and growing at the same time. BTW, I'm glad to see that you are using the correct definition of "quantum" now.

Tom Anderson: After several divisions, a small deviation from the mean would certainly eliminate this one.

This follows your incorrect assumptions.

It follows correct assumptions, namely that cells are discrete and the growth periods are discrete.

But, again, there is no exact time for division.

Yes, there is. The researcher physically divides the culture after set periods of growth.

Although one could code that way in C++...

I'm not going to discuss programming styles in this forum; let's just leave it at pseudo-code.

Why not keep the other half? Why discard it?

Because you would soon end up with an awful lot of cell cultures, and you only need one.

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Tom Anderson - 12:37am Mar 5, 1998 ET (#3733 of 3744)

Curiosity was framed, ignorance killed the cat

Frank,

The argument that placenta is just as differentiated doesn't hold because it would be considered fetal.

Just because it is fetal does not mean it is not differentiated. The placenta is a very specialized and mature organ. And the fact that fetal epithelium and fibroblasts are just as differentiated as those in the adult udder, means there would be little or no difference in growth rates.

Ultimately if you have only one cell to start with, the odds would faavor removal assuming slow rate of growth. But in this case the growth rate is different enough to give good odds for it being maintained especially if you start with more then one Before the first split

That is the essence of the argument. I am saying it is not "different enough", and that you do not start with more than one, and you probably don't even start with one.

------------------------------------------------------------------------

Tom Anderson - 02:00am Mar 5, 1998 ET (#3734 of 3744)

Curiosity was framed, ignorance killed the cat

Ok guys, lets go into more depth here. Since the chance of any one cell being in the half of the culture being discarded, we can assign a binary value to each cell to label it as "Discarded" or "Not discarded". Therefore, we can model the selection of cells by using a binomial random variable distribution.

Let us say that there are 100 cells in the culture, one of which is fetal (we will account for the probability of that one being fetal later). After one growth period, using Frank's growth rates (3:2), there are 200 cells of which 3.96 are fetal and 196.04 are adult. This population will now be split once, creating 3.96 trials for being discarded, each with the probability of 50%; X~Bin(3.96, 0.50). The probability mass function is as follows: b(x; n, p) = (n Choose x)px(1-p)n-x for x=0..n. Therefore, the probability that none of the fetal cells are discarded = P(X=0) = b(0; 3.96, 0.50) = (3.96 C 0)(0.50)0(0.50)3.96 = 0.064 = b(3.96; 3.96, 0.50) = P(X=3.96) = the probability that all of the fetal cells are discarded. The expected value, E(X) = the mean, mu = np = (3.96)(0.50) = 1.98. The variance, V(X) = np(1-p) = 0.99 and the standard deviation, sigma = sqrt(mu) = 1.0. Taking account of the deviation, probability that all of the cells are discarded, then, is P(X>3) = 1-P(X<=3) = (converting to the standard normal) 1-P(Z<(3-3.96)/1) = 1-Phi(-0.96) = 1 - 0.1685 = 0.8315 = 83.15% chance that all of the fetal cells are discarded after the first division. Now we must take account of the probability of the first cell being a fetal cell, so the total probability that a fetal cell is still in the culture after the first division is (2.67E-9)(0.1685) = 4.49E-8 percent.

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Frank Joyce - 11:48am Mar 5, 1998 ET (#3735 of 3744)

Tom:

Your arguement only works if you assume all the cells return to time zero after splitting. Cells don't do this. You must assume that before the 2nd or 3rd splitting there would be 2 divisions by the fetal cells becuase they would be ready to divide after teh previous split and finish another division before the next split. So basically we need a model that accounts for that.

We also need to determine how many doublings it took the origional sample before it reached the max pt and the first split was made. Assuming he did use a larger flask do the the amounbt of tissue excised he could easily have let the cells double several times. Thus starting out with just one cell would yield many before the first split.

------------------------------------------------------------------------

Frank Joyce - 03:39pm Mar 5, 1998 ET (#3736 of 3744)

Tom:

It appears you've also deleted your statement about how many cells are in the blood stream. That was a smart move.

even if the selection is for epithelium it would still work the same because of the way they grow in culture.

I now understand that every time you claim something is a red herring, that's just your way of saying your wrong. This time you actually had to delete your message to make your point.

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Frank Joyce - 03:55pm Mar 5, 1998 ET (#3737 of 3744)

Again as noel states we are working with whole numbers not 3.96 cells.

If we do have several doublings before the first split we would at a minimum have four.and a 1/16th chance all would be deleted. 50% that at least two persist. and 3 other possibilities, any combination of 3 cells, any one cell remaining and a 1/16th chance that all remain. Then two rounds of one double one split, and a round of two doublings and one split. At each time we don't know how many cells would persist but if it did deviate from two the odds would still be far greater that either 3 or 1 would persist. It wouldn't go to 0 by some 50% chance. and if it were three after splitting then it would move up to 6 cells and the odds against being removved even greater.

The real important thing to remember is how many doublings were made before the first division. I can only guess that the cells were allowed to grow a couple of days In a large culture flask before they were at high enough numbers to be split. That could mean anywhere from 4-16 cells present by the first split. At this point I think he would have divided into separate flasks and continued so he wouldn't have to worry about conamination occuring in his only culture.

------------------------------------------------------------------------

Tom Anderson - 04:22pm Mar 5, 1998 ET (#3738 of 3744)

Curiosity was framed, ignorance killed the cat

Frank,

You must assume that before the 2nd or 3rd splitting there would be 2 divisions by the fetal cells becuase they would be ready to divide after teh previous split and finish another division before the next split.

That is already accounted for by the relative growth rate figure of 3 to 2. It does not matter when you split it in respect to each individual cell so long as the relative growth rate for all of them is constant.

We also need to determine how many doublings it took the origional sample before it reached the max pt and the first split was made.

So go ahead and determine it. It really does not effect much considering the real limitation here is the probability of selecting a fetal cell in the original sample in the first place. Whether that one would grow into 1.25 or 2.75 or 5 out of a hundred does not account for much. Even if you started out with a sample of 100/100 fetal cells and no adult cells, that would still be dependent upon the probability of selecting that particular sample.

It appears you've also deleted your statement about how many cells are in the blood stream.

First of all, I haven't deleted anything. Second of all, I never made any claim as to the number of cells in the blood stream.

even if the selection is for epithelium it would still work the same because of the way they grow in culture.

No, actually it makes no difference whatsoever because this is entirely irrelevant to anything.

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Tom Anderson - 04:26pm Mar 5, 1998 ET (#3739 of 3744)

Curiosity was framed, ignorance killed the cat

No, actually it makes no difference whatsoever because this is entirely irrelevant to anything.

I now understand that every time you claim something is a red herring, that's just your way of saying your wrong. This time you actually had to delete your message to make your point.

Every time I tell you that your statements are red herring, they are. Stop bringing useless, irrelevant statements into the discussion and I'll stop calling you on it. The problem of course is that you would suddenly have nothing to say at all. Nothing I've argued against you was wrong, and you couldn't even prove something wrong if you were arguing with a tree. Once again, I've never deleted my messages, and once again, your ad hominim attack is another red herring because you have no argument to make.

Again as noel states we are working with whole numbers not 3.96 cells.

Actually, I'm the one who pointed out that cells are discrete. However, my use of non-integers here simply reflects your growth rate figure and allows for some cells not to have finished dividing, or started again. This accounts for probabilities dependent on the fact that all cells do not stop dividing at the culture division and then restart again.

It wouldn't go to 0 by some 50% chance. and if it were three after splitting then it would move up to 6 cells and the odds against being removved even greater.

The mean chance of any one cell being discarded is always 50%. There is also a variance.

That could mean anywhere from 4-16 cells present by the first split.

Let's say there are 16 fetal cells, which means there are 792 adult cells, for a total of 808 cells with a 3 to 2 growth rate. This is still only 2 fetal cells for every 98 adult cells.

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Tom Anderson - 04:28pm Mar 5, 1998 ET (#3740 of 3744)

Curiosity was framed, ignorance killed the cat

BTW, Frank, you still have not given any evidence that placental epithilia would grow any faster than mammary epithelia. This 3 to 2 number sounds like you pulled it out of your ass.

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Noel Yap - 04:49pm Mar 5, 1998 ET (#3741 of 3744)

Frank Joyce: So the model must assume that the adult cells will stay within a Constant range.

And so it was written, and so it shall become.

Frank Joyce: I was actually trying to avoid the word random since that seems to be an entire topic in here

Yeah, it seems the Watchers don't think it's appropriate for this board. You could, however, use the stochastic (it doesn't have the same connotations ;)

Frank Joyce: I think in a good model we can't assume that mitosis goes back to time 0 after the split.

I agree. This is another reason why continuous time models are easier to deal with.

Tom Anderson: The twice a day figure was just used as an estimation in saying 730 splits due to twice a day for one year, but replace that number with 600 or 800 and it still does not amount to much of a difference.

This number is very important when trying to figure out the probabilities for zero fetal cell population.

Tom Anderson: Yes, I am assuming uniform distribution because there is no reason for dead or dying fetal placenta cells to accumulate in the udder.

This makes sense. Frank, do you have evidence to the contrary?

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Noel Yap - 04:50pm Mar 5, 1998 ET (#3742 of 3744)

Tom Anderson: Yes, we are dealing with probabilities, but there will not be any fetal cell growth after the second split if they were all eliminated by the first one, even though probability would show an indiscrete value.

I see your point, now. I might have something in a few weeks to reflect this.

Tom Anderson: But continuous time would lead to errors because the experiment actually was done in discrete amounts of growth per division rather than slowly dividing and growing at the same time.

I still don't see how they're able to do this considering that the cells divide at different rates.

Tom Anderson: I'm glad to see that you are using the correct definition of "quantum" now.

Well, using "my" definition, you are doing calculations at the quantum level (ie discrete) while I am not (ie continuous.) I'll try to stick to terminology that we all understand from now on.

Tom Anderson: It follows correct assumptions, namely that cells are discrete and the growth periods are discrete.

Again, according to Frank, the time between divisions is not exact. IOW, division periods cannot be taken as discrete.

Tom Anderson: Yes, there is. The researcher physically divides the culture after set periods of growth.

But the number of periods of growth is fuzzy.

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Noel Yap - 04:50pm Mar 5, 1998 ET (#3743 of 3744)

Tom Anderson: Therefore, we can model the selection of cells by using a binomial random variable distribution.

OK. I'm assuming your math is correct. All that has to be done now is to generalise it for n divisions.

When I've got my new and improved model, we'll compare results. Assuming both models are correct, they should somewhat agree.

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Tom Anderson - 06:56pm Mar 5, 1998 ET (#3744 of 3744)4212

Curiosity was framed, ignorance killed the cat

Ok, let me put it another way. Instead of searching for better mathematical models and so forth, let's just keep the discussion focused on what is important. Even if you were to say that a fetal cell were guaranteed to be selected if it were present in the sample, then there would still be less than a ten-millionth of a percent probability of that occurring.

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Cliff Beall - 09:10pm Mar 5, 1998 ET (#3744 of 3751)4213

Certainty: most of the time it ain't...

I think that what is important is that Dolly's cells are showing signs of abnormal aging. This is a mere assumption, of course, but I can not imagine Campbell and Wilmut submitting Dolly's cells to an independent lab without already knowing what the results will be. They are certainly capable of doing the tests, themselves. And it makes sense to me that they would seek an independent verification only if the expected result is positive. I am, therefore, assuming that Dolly's creators have already found these signs and want independent verification of them.

I think each of you guys would agree that regardless of any probability you might calculate, a verification that Dolly's cells are showing signs of abnormal aging would put to rest the "heresy" that Dolly was cloned from a fetal cell, and would tend to restore some of the standing, within the scientific community, that Campbell and Wimut lost when it was established that they could not document all their sources with respect to the cloning of Dolly. They can't get it all back, of course, but if they can "prove" that they did, in fact, used an adult cell to clone Dolly, it should quiet most of their detractors. I would guess that this is what they are after, at this point.

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Frank Joyce - 09:31pm Mar 5, 1998 ET (#3745 of 3751)4214

Tom:

It does matter because we are talking about cycling times. the cycling time is not reset after each split!!!! You treat the problem as if it were a linear rate like miles/distance and it is not.

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CNN Community Staff - 02:34am Mar 6, 1998 ET (#3746 of 3751)4217

Frank and Tom....

Please debate the issues... Please do not continue to attack each other personally. Personal attacks are not allowed here. If there are any more personal attacks, the messages will be removed as well as access to the message board. When you joined this message board, you agreed to follow our rules.

We look forward to you continued participation within the guidelines.

CNN Staff

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Bob Janitor - 03:16am Mar 6, 1998 ET (#3747 of 3751)4218

Frank and Tom

Now that's funny... CNN staff actually calling people by name.

We look forward to you continued participation within the guidelines.

You set up boards for scientific, moral, political and religious debate... you must expect personal attacks to some degree. I think Frank and Tom haven't desevered getting banned for what they've said, or will say based on the content of their past material. They've both been quite objective, and I think the content of this board is far more intelligent than any other on CNN.

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Sree - 04:55pm Mar 6, 1998 ET (#3748 of 3751)4219

A person is never born great,

he may have born with very high IQ

but Albert Einstien could be a evil genious Eg. he may be very good cracker not hacker

Gandhi may be some one like Hitler, Howard Stern

If they are not brought up with right idealogical environment also should get an inspiration from his sorrroundings may be if Gandhi never been to South Africa instead he was in ethopia he would never become such a great person.

the above statement dosen't mean that I dont respect Gandhi I have a Great respect for him

May be clonning is just 1% of producing a great person

If we devote rest of the 99% effort on the kids who already born ?????

Think it out guys?

What is the pupose of clonning great people if we still have to 99% of the work ahead of us to make the clone as great the original let alone the knowledge of the circumstances that made the original get his/her inspiration to make him follow a path of greatness, let alone another fact the clone knows thet he is a clone of a great person why would he listen to us nobodies, so above this 99% effort we have to fight the clones attitude

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Frank Joyce - 09:12pm Mar 6, 1998 ET (#3749 of 3751)4221

Having spoken with some of the professors oncampus I found something interesting.

For there to be fetal cells in the blood stream there had to have been leakage in the placenta. This would have caused a maternal immune response to the fetus. If the leak was large enough teh mother could have died as well as the fgetus. this might explain why the donor sheep died and why there is no daughter lamb to get DNA from.

These fetal cells be they from the placenta or not would have a faster rate of growth becuase placenta is continuously growing to match the rate of the growth of the fetus and its need for nutrients.

The math models represented thus far would make contamination of cultures impossible yet its common in labs.

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Frank Joyce - 09:18pm Mar 6, 1998 ET (#3750 of 3751)4221

I do beleive someone mentioned that the cells were frozen, thus after the cells were brought up they may well have been distributed into individual cryovials and frozen. thus each sample would be thawed and brought up separately a few days before each event.

Finally, the reason that wilmut sent dolly out for investigation may simply be becuase his lab does't do that particular test routinely. Keep in mind that teh aging that he is looking at would be do to shortening of telomeres. I discussed this earlier. It is believed that telomeres would return to normal lenghts in the cloning process do to exposure to telomerase.

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Frank Joyce - 09:23pm Mar 6, 1998 ET (#3751 of 3751)4222

All of this suggests that fetal cells would be present in the blood and may have been present in greater quantities than we previously thought. It suggests that Fetal cells had a good probability of being in the culture. And ultimately that my arguments that fetal cells are eaiser to clone were the basis of an unintentional selection are in order.

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Cliff Beall - 11:28pm Mar 6, 1998 ET (#3752 of 3752)4223

Certainty: most of the time it ain't...

Possibly. But the AgBiotech News & Information (ANI) article to which I earlier provided a link indicates that they were running these types of tests on Dolly before September of last year and were finding indications of abnormality. The article: Cloning Miscarriages & Genetic Alterations - ANI Sep 97, reports that "some of Dolly's chromosomes have undergone subtle structural changes usually found only in cells from older animals."

In view of the subsequent controversy, if it is actually true that Dolly's cell are aging abnormally, I think if I were Campbell or Wilmut, I would want independent verification of this to show that Dolly was cloned from an adult cell. Before the controversy, they would simply have done their own tests (or had them done privately) and publish the results. But now, they probably feel that they need independent verification to quiet their critics. I am again providing the link to the AgBiotech News & Information (ANI) site, in case you would like to review the article:

http://www.cabi.org/whatsnew/cloneani.htm

I think the evidence is that it was at most a very slight chance that Dolly was cloned from a fetal cell. From the beginning, Dawn indicated that the chance was very slight, but that a slight chance did exist. My argument with Tom and Bob, in the beginning, was that they seemed to admit no chance at all.

The chance was very slight--never more--but it did exist. I think that is about all you can say about it.

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Richard Irby - 04:30am Mar 7, 1998 ET (#3753 of 3755)4224

I think that cloning is a great idea as long as all we clone are good looking chicks.

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Cliff Beall - 12:31pm Mar 7, 1998 ET (#3754 of 3755)4225

Certainty: most of the time it ain't...

But as Tommy Smothers might say, "Cloning isn't just a fun thing." And it might be even less a fun thing if the cells of the good looking chicks prematurely age.

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Frank Joyce - 09:04pm Mar 7, 1998 ET (#3755 of 3755)4227

Cliff:

interesting article. I wish he would state exactly what the Subtle changes were.

I did not hear the origional arguments that Dawn made. I don't know if she considered the possibility of the fetal cells being in the blood as a cuase or effect of the sheeps death. In either cae they would have been far more present than expected.

In the end we'll have to wait to see what is possibly wrong with Dolly.

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Cliff Beall - 01:51am Mar 8, 1998 ET (#3756 of 3756)4229

Certainty: most of the time it ain't...

On Jan 30, Dawn said the following: "This just in from 1/30 issue of Science: Dolly may not actually be a clone from a somatic cell. The cells were taken from a frozen stock of mammary cells of a pregnant ewe, who had died... Fetal cells do circulate in pregnant females, so this cell could have been from the fetus and not the adult animal."

On Feb 8, she elaborated: "Certain cells have the capacity of motility... phagocytes, for example. Embryonic cells are even more motile, because they must find their way to the right spot in the embryo. These cells can leave the bloodstream, cross the basement membrane, etc... See the January 30, p. 635 issue of "Science" for a letter by two prominent scientists who don't think Dolly's parentage is 100% certain."

Finally, on Feb 9, she quoted Stites and Terr. On Feb 28, I posted the entire contents of this post by Dawn in response to a question by Tom. I assume you read that post.

That the death of the pregnant sheep might be the cause of, or the result of, an increase in the number of fetal cells intermixed with the adult sheep's cells, is an interesting idea. If Dawn were to choose to address that, I would be interested in what she might have to say. But I think the idea is likely to turn out to be beside the point. If it is true that Dolly's cells are showing abnormal signs of aging, I would suspect it is a result of being cloned from a six year old adult cell. (Or perhaps, it is the result of being cloned from a cell from a six year old sheep that had died.)

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William Geddings - 04:22am Mar 8, 1998 ET (#3757 of 3757)4230

"WOW" Weird stuff here indeed. Yall don't think this will get into the thinking that Hitler had in his trying to make a supreme race or something to that effect Do you? Its so easy to get caught up in thinking that one is able to have the power of creation in ones hand & become vain in their ideas. Just as a one has said things such as cloning nothin but "Good looking chicks" Well what does "one" concider to be Good Looking ? Their are many diffrent looks & styles & people in the world. Thats what makes up our excitement in life. Even though the person may have meant nothin by that coment other than to pick fun,which is o.k also 8). But seriosly I hope we donot get carried away with it to where it is no laughing matter no more.Just as Hitler was no laughing matter.

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Carl Nicolai - 12:09pm Mar 8, 1998 ET (#3758 of 3758)4231

Located in Taipei Taiwan

In spite of what Hawking said at the white house the Euro states are banning human cloning.

"The signatories are Denmark, Finland, France, Greece, Iceland, Luxembourg, Norway, Portugal, Romania, San Marino, Spain, Sweden and Turkey."

Not enough to start the Clone Wars yet, but consider just what this means. Reproductive choices are either going to be made by Individuals or the state. There dosent seem to be a middle ground.

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Cliff Beall - 01:03pm Mar 8, 1998 ET (#3759 of 3759)4232

Certainty: most of the time it ain't...

William, I think you have missed the main points of the discussion. Basically, in the last several posts, we have been discussing the difficulties and problems associated with cloning. In the last month, we have mainly discussed the chances that Dolly was cloned from a fetal cell rather that from an adult somatic cell. Other topics of discussion have included the nature of differentiation of cells and it's effect on cloning success, and legal issues regarding reproduction options. It these types of things are your bag, you have come to the right place, However:

Your comment that "I hope we donot get carried away with it" and your reference to Hitler would have fit right in a couple of months ago after Seed did his thing, and this messageboard literally went crazy. But, since then--for the most part--sanity has returned. We want to keep it that way. If you're interested only in the "provocative" aspects of cloning, I doubt if you will find much of interest here.

Governments will continue to regulate (possibly) dangerous medical procedure. Does it surprise you that the people who have the power to rule will use it to rule? I am not surprised by this. My surprise is that stem cell research has not already been significantly limited. After the Seed scare, I am surprised things are returning to normal so soon.

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Carl Nicolai - 01:44pm Mar 8, 1998 ET (#3760 of 3760)4233

Located in Taipei Taiwan

Ref. Cliff Beall #3759 Cliff we are not talking about regulating a medical practice. Banning is not regulating. The only intrest society has in "regulating" reproduction (of concenting adults) is the possibility of damage to a future child.

No one wants to bring a malformed human into the world.

This is going to cost a lot of money initially. By the time it gets cheap we will know the risks involved.

One way to handle risks is to have insurnce. The insurance companies are experts at evaluating risks.

BTW no insurance company will insure the safety of a necular reactor.

Cloning for reproduction has just become another political football.

As a side note the genetic banks that CNN has refrence to are amaizing. Six years ago I started a study on the compressability of genetic data as a means of determining coding efficency. At that time only a few samples were available. Now I have a lot of data to play with. Don't know if it will ammount to anything but as far as I know no one else is doing it.

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Tom Anderson - 07:18pm Mar 8, 1998 ET (#3761 of 3762)4234

Curiosity was framed, ignorance killed the cat

Ahh, finally, midterms are over!

I see the "staff" has been at work again. Always when I point out the flaws in frank's arguments, too. No matter.

Frank,

The reason Wilmut admitted there would be fetal cells in the blood stream is not because the placenta would have ruptured; that is not what killed the parent since they would not have frozen the cells of a sheep for research use unless they killed a perfectly healthy animal. The reason there may have been fetal cells in the mother's bloodstream is because the membrane separating the two bloodstreams is that of the fetus, since the mother's side of the membrane dissolves earlier in development. This means that, as the placental cells die and get replaced like any other cell, they detach from the membrane and enter the mother's bloodstream in order to be eliminated in the kidney or liver. I figured a PhD candidate would have known that.

Richard & William,

Please view my Cloning FAQ.

Carl,

BTW no insurance company will insure the safety of a necular reactor.

Why not? So far, they have been totally reliable. And if there ever were an accident, there would be so many people making a claim against the power company that both the power company and insurance company could just declare bankrupsy. But, in the meantime, it is free money for the insurance company seeing as there has never been an unsafe reactor in the United States. Anyway, isn't nuclear reactor safety insured by the Nuclear Regulatory Commission?

Cloning for reproduction has just become another political football.

Unfortunately. It certainly should not be so.

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Frank Joyce - 07:21pm Mar 8, 1998 ET (#3762 of 3762)4235

I don't think it's just insurance companies and government that we need to worry about. religious leaders are strongly against cloning of people. This presents a much greater obstacle. Statements such as " you cannot clone a human soul." can be taken way out of context by fundamentalists.

Carl:

Tell us more about your study

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Cliff Beall - 08:07pm Mar 8, 1998 ET (#3763 of 3763)4536

Certainty: most of the time it ain't...

Carl, I would have to say that banning is a type of regulating. I would agree that the only real interest that society has in regulating reproduction (other than population control, perhaps) is the possibility of damage to a future child. But as long as the stem cell research is not impeded and animal studies are allowed to continue, I see no particular harm in the European ban, or, for that matter, the proposed American ban.

True enough, perhaps. But some people are willing to accept a greater risk than others. I have no doubt that some people will continue to insist that the risks of human cloning are minimal, even if it is firmly established that Dolly's cells are showing signs of premature age.

Correct me if I am wrong, but my understanding is that dead cells can not be cloned using current technology. I was under the impression that live fetal cells were able to enter the mother's body.

Yes, that is the other side of the coin.

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Cliff Beall - 11:06pm Mar 8, 1998 ET (#3764 of 3769)4237

Certainty: most of the time it ain't...

Regarding Tom's suggestion to Richard and William that they view Tom's Cloning FAQ:

If Richard and William find disagreement with some of the opinions expressed by Tom in his FAQ--particularly those having to do with the ethics of cloning--as I do, I suggest they visit an FAQ published by New Scientist magazine for a different point of view. To access the New Scientist FAQ, click the address below:

<A HREF="http://www.nsplus.com/nsplus/insight/clone/faq.html"> http://www.nsplus.com/nsplus/insight/clone/faq.html </A>

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Carl Nicolai - 12:02am Mar 9, 1998 ET (#3765 of 3769)4238

Located in Taipei Taiwan

Ref. Frank Joyce #3762. The genetic code is interesting for several reasons. Coding is used for three basic reasons. Data error detection and correction, data compression, and cryptography. In biology we could add the matainance of structural integrety. (such as using a twisted form of starch to form cellulose)

Now data is not Information. Information being "The receipt of that energy that changes the probability assignment of a well formed question". It is interesting that data that contains pure information is indistinguishable from purely random data.

But if the data on average contains less than one bit of information it can be compressed. The correlation of various elements of the genetic code have been studied but the compressability of various segments of the genetic code has not.(at least to my knowledge)

Since the code can be listed as a one dimensional array that codes for a three dimensional structure it could be looked at as a complex crypographic system that incorporates the other uses for coding.

I would like to know more about this.

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David Bordelon - 03:44am Mar 9, 1998 ET (#3766 of 3769)4239

Blind faith in anything will get you killed

There should be continued(and controlled) research into genetic cloning. Why? Think not of cloning the whole body, but of the body part. How about burn victims getting their own skin without the loss of skin elsewhere. Or, the blind able to see, the quadrapaligic able to walk, and a whole host of other applications. You have kidney disease and no match? Grow your own kidney to transplant. The research should continue, but in a controled manner. When we ban something, that allows it to grow uncontrolled in horrorific ways. Example: Prohibition and Abortion. People died because alcohol and abortion was banned in this country. Poisoned alcohol due to lack of controls, and the ever deadly clothes hanger which killed young girls too scared to face the shame.

You think the possibility of cloning is scary, try uncontrolled hidden lab cloning.

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Frank Joyce - 12:30pm Mar 9, 1998 ET (#3767 of 3769)4240

CNN staff:

I did my best but it seems the other party just can't stop making his attacks.

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Frank Joyce - 12:37pm Mar 9, 1998 ET (#3768 of 3769)4241

Fetal cells:

Like I said, no one knows how the lamb died. If there was a rupture there would be many more cells present and the lamb would have continued to be healthy for a while. Later it would have dies and the fetus as well. If it happened the other way around the mother would most likely have an immune response to the fetus. the fetus would either be destroyed or born enemic.

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Frank Joyce - 12:46pm Mar 9, 1998 ET (#3769 of 3769)4242

Carl:

Have you looked at satellite viruses? They do some very interesting things with their DNA. This includes coding for genes within the same strip of DNA but in opposite directions. In other words they overlap. Transplicing is also interesting. I think the higher up you go the less compressed things will be though. Compressing may be efficient but it also makes mutations far more damaging.

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Bob Janitor - 09:41pm Mar 9, 1998 ET (#3769 of 3772)4243

there has never been an unsafe reactor in the United States.

Huh? Remember Three Mile Island? And in addition, there have been quite a few "incidents" with test reactors... one in Idaho comes to mind... and has the military been forthcoming with all of their accidents? I doubt it. Remember, the military has more nuclear reactors than any other single organization, and more than are used for commercial power production in the US.

Don't get me wrong, nuclear power is a good source of energy and with our current technology it's quite safe. However, the US *has* had its share of problems with nuclear technology.

But, if you can insure car collisions (which are relatively frequent) and humans not dying, I suppose you can insure nuclear power plants :-).

BTW, has Wilmut announced any progress on the second clone?

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Cliff Beall - 11:32pm Mar 9, 1998 ET (#3770 of 3772)4244

Certainty: most of the time it ain't...

The cloning of skin has already occurred. Dermagraft-TC is the name of a product cultured from infant foreskins. You may be interested in a press release by Advanced Tissue Sciences. If so click the address below:

http://news.pharmaceuticalonline.com/industry-news/19971021-181.html

For a more general article of the myriad of technologies in this area including synthetic skin products, click the address below:

http://www.devicelink.com/mddi/archive/97/02/011.html

With respect to vital organs, however, the news is not so good. First of all, nobody has the faintest idea how an individual vital organ could be cloned. To successfully clone an individual organ, it would appear that you would have to be able to manipulate DNA on a one to one basis. Biologists can not now do that, but instead insert genes at random. Second, the associated problems with growing an individual vital organ would be incredible, even if you could do the appropriate manipulation of the DNA.

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Cliff Beall - 11:34pm Mar 9, 1998 ET (#3771 of 3772)4245

Certainty: most of the time it ain't...

Some time back, on Feb 9 at 03:32am, Bob Janitor posted an explanation of some of the associated problems. He said it better than I can, so I will quote from his post. I don't think he will mind.

Bob's explanation follows:

"You can't just clone an organ. Organs are highly specialized groups of tissue that develop to perform a specific function. They are protected by the immune system and body cavity, fed nutrients by each other, and are under neural network control. You just can't get a cell culture to develop into a working, bare organ that would be good for transplant and then stick it in a freezer. To bioengineer something like that, which would have to kept alive by technological life support machinery, is going to take a *LONG* time, if we ever see it. And even then, does the organ have an immune system to protect itself during development? How would this affect the body once it was transplanted?"

Hopefully, the stem cell research and animal cloning will be allowed to continue. I think it will due to the demonstrated medical advantage. Human cloning of adult cells is not acceptable until it proven to be safe. My preference would be that the FDA regulate human cloning research. But I think there is going to be a law passed by the congress and signed by the President to ban human cloning for the purpose of reproduction for a period of 10 years. I think we can live with that provided the stem cell research is allowed to continue.

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Cliff Beall - 11:36pm Mar 9, 1998 ET (#3772 of 3772)4246

Certainty: most of the time it ain't...

Yes, the remark was unfortunate. I think he is wrong anyway. Unless I have misunderstood, the PhD's have indicated that live fetal cells can be present in the mother's body, not just dead cells discarded by the placenta. But I will await Tom's reply.

At least, we do not know how she died. However, I would seriously doubt if a pregnant sheep was intentionally killed for the express purpose of using her cells in a cloning experiment. I would suspect she died due to an accident of some sort, or perhaps she died giving birth. I can't think of any other possibility that would cause the scientists to think the cells might be usable. In any case, I would suppose that since they had the cells available, they decided to use them in an experiment.

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Cliff Beall - 12:12am Mar 10, 1998 ET (#3773 of 3773)

Certainty: most of the time it ain't...

Not that I know of. I check the Roslin Institute Online press release site periodically. They were busy with press releases in 1997, but in 1998, so far, they have been quiet. If anyone is interested, click the address below for a link to the Roslin Institute Online site:

<A HREF="http://www2.ri.bbsrc.ac.uk/library/research/cloning/cloning.html#Press"> http://www2.ri.bbsrc.ac.uk/library/research/cloning/cloning.html#Press </A>

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David Bordelon - 03:51am Mar 10, 1998 ET (#3774 of 3778)

Blind faith in anything will get you killed

Cliff Beall, the lack of technology in the growth of an organ is why I'm in favor of continued research. I, personally, would love to have my lungs replaced in 20 years rather than suffer the asbestosis I can expect from my 6yrs on a ship. I strongly don't believe I will ever see it happen, but I do believe it will in time.

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Benjamin Post - 07:37am Mar 10, 1998 ET (#3775 of 3778)

RUOK2?

Your scientists got so wrapped up in wether they could, that they didn't stop to wonder if they should...(Jurassic Park)

The talk right now, is very much on the tecnicalities, but as I am not well versed in this field, I'm more interested in the ethics involved:

Suppose that I am cloned already at the fetal stage. Somehow I am allowed to "grow a brain", my clone is not. I live my own normal life, while my clone is in relatively dormant storrage somewhere. All of a sudden, my heart stops working properly. What do we do? The heart of my clone is removed, and inserted into my body; A perfect match! I continue to live a relatively normal life. As I am really using my own heart, the risk of rejection is minimal, so I will probably never have to have another operation.

Isn't that convenient? And as far as I know, we might even be able to do such a thing with the technology available today. This leaves only the philosophical discussion of when conscience is concieved. Have you had a life, if you have never had a thought? We use the organs of braindead individuals today, so what if we were to create an identical twin, braindead from the moment of conception?

And how about the idea of combining the genes of the unfortunate infertile couples to produce an infant? Is this really any different from what mother nature herself does? Is it playing God? Is it mimicking God? -Or is it just some sort of celestial copyright violation?

Provoking thoughts? -I certainly hope so. Please respond, one and all...

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Frank Joyce - 12:47pm Mar 10, 1998 ET (#3776 of 3778)

Benjamin Post:

Interesting Idea. But where are people supposed to store these identicle twins until they need them? how much would it cost to store one Vs. just getting a donor organ somewhere else? as far as I know, Frozen organs don't work for transplant. Babies born without a brain don't live long or develope normally when kept on machines so how would an adult be able to use a babies organs?

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Dawn Willis - 07:12pm Mar 10, 1998 ET (#3777 of 3778)

I'm glad you guys have stopped building models of the growth of cells in culture. There are too many assumptions in the models, and I learned long ago that cells don't always do what you expect--the lot of serum can make a big difference in the outcome. Regarding Dolly's parentage, I have no reason to believe that the pregnant ewe was dead at the time the tissue was taken, or that the pregnancy was anything other than normal. My impression from Wilmut's interview was that the pregnant ewe mammary tissue was just something that he happened to have around in the freezer for other purposes. He thawed out the vial several years after collecting the tissue, grew up the cells, and used the cells that grew out for the experiments. Because he didn't expect the cloning to work, he didn't validate the source as carefully as he should have. The chance that there was a fetal cell is small. Not only placental cells, but small numbers of fetal and other cells go back and forth across the placental membrane, but not usually in quantities great enough to elicit an immune reponse in the mother (maternal immune systems are depressed during pregnancy). Still, this slim possibility is why the experiment must be repeated with non-pregnant nuclear donors.

There was some talk about differentiation a while back. To speak of differentiation, in standard developmental biology talk, you must have a multicellular organism with specialized cell types. A zygote, being only one cell, is not differentiated. There are grades of differentiation. The embryonic stem cell of the first few cell divisions can give rise to all kinds of cells; it is totipotent. There are pluripotent blood stem cells that give rise to all the components, red and white, of the blood. There are oligopotent stem cells that line the gut and give rise to various cell types of the intestine. Then there are stem cells in the basal layer of the skin that can only give rise to skin cells through various steps of

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Dawn Willis - 07:27pm Mar 10, 1998 ET (#3778 of 3778)

Tom Anderson: Down's syndrome does indeed occur from non-disjunction during meiosis. Grifo and Zhang (NYU) have preliminary evidence suggesting that there is an age-related change in the human egg cytoplasm's capacity to form the apparatus required for meiotic division. Their data indicate that young egg cytoplasm prevents aneuploidy (abnormal numbers of chromosomes) in old nuclei. Next, they plan to analyze reconstructed eggs to determine whether they can cause aneuploidy in young nuclei with old cytoplasm. If they get really good at this, they will have an alternative to total egg donation, and give older mothers and infertile women a chance to bear genetically related offspring. This is a very "fertile" field of research.

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Cliff Beall - 11:23pm Mar 10, 1998 ET (#3779 of 3781)

Certainty: most of the time it ain't...

There is a great deal of research going on, and while some of it might eventually make the growth of isolated organs possible, though extremely expensive, the research is more likely to result in much less expensive solutions that are actually practical. For example, current research is very likely to result in vital organs grown in animals that are appropriate for transplant into humans. How do you feel about that? If biotech companies can raise pigs that have lungs, a heart, and a liver that can be transplanted into humans without rejection, would you accept organs grown in this way?

Well, if you wish to be encouraged about the ethics of the situation, you might access Tom Anderson's <A HREF="http://attila.stevens-tech.edu/~tanderso/cloning/"> cloning FAQ here </A>.

Personally, I think what you are proposing is unethical in the extreme and likely to be illegal for a very long time.

I am sure you are capable of making a decision on this matter that is consistent with your conscience. But I am of the opinion that there is not a nation on the face of the earth that would condone the intentional introduction of a severe birth defect, such as you describe, into a child.

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Cliff Beall - 11:27pm Mar 10, 1998 ET (#3780 of 3781)

Certainty: most of the time it ain't...

It is my understanding that there is widespread use of organs from aborted anencephalic infants, as well as other aborted infants. However, if an anencephalic infant is brought to term, it is illegal to take the organs until after the hindbrain is completely dead and the other organs are, as a result, useless. Given the circumstances, it don't make a lick of sense to me. To hell with ethics. Do the right thing.

However, to *intentionally* introduce this type of birth defect into a child is one of the most abhorrent, despicable things I can imagine.

Apparently I took your words: "frozen stock of mammary cells of a pregnant ewe, who had died," too literally. Sorry I misunderstood your intent.

Another misunderstanding apparently. I had assumed you obtained the information about the frozen cells from the letter in 1/30 issue of Science by the two "prominent scientists." One question: did these two scientists, to which you referred in your Feb 9 post, give a reason as to why they were bringing up this problem in a letter to "Science"? (I have imagined that they might be researchers who, after having been unable to duplicate Wilmut's results, had communicated that to Wilmut and had subsequently obtained the information about the frozen cells from Wilmut during their discussions regarding their lack of success.)

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Cliff Beall - 11:31pm Mar 10, 1998 ET (#3781 of 3781)

Certainty: most of the time it ain't...

Right. But if I understood Carl correctly, and Carl can correct me if I am wrong, in his "degree of differentiation" idea, Carl was looking for something like a mathematical relationship (weigh, measure, rank) with which logical operators could be used to indicate degree of cloning success with respect to specific types of cells, and their degree of differentiation.

I have taken the position that some things in nature simply are, or they are not, and do not necessarily have a discernable mathematical relationship. An interesting example of what I am talking about is the iron-carbon equilibrium diagram. Add carbon to iron to make steel and the temperature boundaries at which phase changes occur, changes. Add differing amounts of carbon, and the temperature boundaries change differently, and in surprising ways. The diagram does not admit to any simple (or complex) mathematical relationship that I know of, and it is my understanding that the iron-carbon diagram had to be constructed strictly from experimental data.

It would appear to me that a late term fetal liver cell would have be as differentiated as an adult liver cell. Otherwise, the fetal cell would be unable to produce the correct proteins. Therefore, if there is a difference in the rate of cloning success between fetal cells and adult cells, it would have to be a result of other factors. I would not be too surprised if it is eventually determined that more highly differentiated cells may work better, in some cases, that other, less highly differentiated cells, and the only way to make a final determination is experimentation. I would appreciate your comments.

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Carl Nicolai - 02:29am Mar 11, 1998 ET (#3782 of 3782)

Located in Taipei Taiwan

Ref. Dawn Willis - #3777 and Cliff Beall - #3781 Thanks for addressing my problems with the concept of cell differentiation. The concepts of totipotent, pluripotent, and oligopotent cells helps a lot.

The analogy that seems to work is that the nucelar structure is like the blueprint and the cytoplasm is like the factory that makes things from the blueprint.

Now having a complete set of blueprints doesent help you build an entire complex object if the machinary to do the various jobs is not present or can not function because of space limitations or not having the ability to operate.(sorry we have no 3 phase power)

So I see two highly orthogonal comcepts at work. one is the degree of specilization and the other is differentation, meaning not being able to give rise to other types of cells.

A hair folicle may produce only one kind of protein while a liver cell many thousands. They may be equally differentated however if they both lack the same, or equivelent, ability to easily be caused to form another type of cell.

This process would require a way of selecting which the RNA functions could be expressed, or suppressed. Also which types of RNA are involved. All three?

The next question that comes to mind is dedifferentiated cells. We know that older peoples cells become less specalized in the sence that they dont produce what they use to and are more capable of reverting to other types of cells. Does anyone have a clue as to why and how this occurs?

Years ago I read that cells raised outside the body can only undergo about 50 divisions while inside the body the number is much larger. Any idea why?

Im still trying to figure out in what way the cytoplasm opperates in this scheme and what other things go on inside the nucelar membrane besides RNA production.

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Cliff Beall - 03:07am Mar 11, 1998 ET (#3783 of 3793)

Certainty: most of the time it ain't...

If this is the meaning of differentiation, I have misunderstood. I have taken the word differentiation as just another word for specialization: cells in different parts of the body start producing "different" proteins as appropriate for the type of cells they are. In other words, it has become specialized. As I have understood it, differentiation is just a state of being, not an indication of flexibility or ability (or inability) to change. Of course, the nature of a state of being can have an effect on the ability to change. Have I missed the point?

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Bob Janitor - 03:29am Mar 11, 1998 ET (#3784 of 3793)

Years ago I read that cells raised outside the body can only undergo about 50 divisions while inside the body the number is much larger. Any idea why?

No... inside the body they can only divide 50 times as well. It's due to telomer shortening.

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Tom Anderson - 04:41am Mar 11, 1998 ET (#3785 of 3793)

Curiosity was framed, ignorance killed the cat

Dawn,

A zygote transcribes only a select few of its genes, therefore it is as differentiated as any other cell.

Cliff,

If you find error in my FAQ, please point it out.

There *is* a mathematical relationship regarding iron and carbon, both in temperature vs state and in state vs strength.

Bob,

A positive statement as to the involvement telomeres play in any role is purely speculative.

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Carl Nicolai - 05:03am Mar 11, 1998 ET (#3786 of 3793)

Located in Taipei Taiwan

Cliff #3783. I dont know either I'm just trying to understand in some meaningfull way.

Bob #3784. It seems that a lot of people have talked about telomer shortening. Also some have mentioned a repair process, and some cancer cells dont have this problem at all. Is this something that relates to differentiation or specialization or division rate?

BTW some of the base listings have "N"s in them I understand this means that no one knows what is in that position. Does this have something to do with the cleaving chemicals? Why do some listings contain capital and small letters? What do the small letters mean?

Thanks

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David Bordelon - 11:24am Mar 11, 1998 ET (#3787 of 3793)

Blind faith in anything will get you killed

Cliff Beall, if a new set of lungs were grown for me in a pig, not only would I accept them, but I would hold a pig roast to celebrate. Never look a gift horse in the mouth.

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V. Manu - 02:14pm Mar 11, 1998 ET (#3788 of 3793)

Lessons of Manu:

Pursuit of knowledge is natural, normal and fulfilling if it proceeds in a life-supporting direction - in the short term and long term.

Wanted : Mature and wise guidance and accountability of scientists and the scientific community!

Genetic engineering and cloning are clowning. They are jokes; but we shouldn't be laughing.

Modern Science has proven to be little more than child's play with high stakes and without proper adult supervision and the observance of the rule : Safety First!

It's ironic that scientist have to rely on unscientific means; "prayer", luck , chance, etc. to keep us from 'doinging ourselves in' with their weapons of mass destruction?

We've made a mess in the atomic field; and now we are crapping in the field of the building blocks (genes) of our bodies - human, animals and plants!

My friends, I hope that in your childlike fascination with the titillating promises, discoveries and inventions of Modern Science you do no loose a mature perspective of the Bigger Picture - the importance of, and the threat to, human existence!

The "blessings" of Science has not balanced it's curses. The human race has never been so close to it's extinction until Science hit the scene!

It is very sad that, in our delusion and ignorance, we do not realize how precious human existence is, the immense fulfillment it offers.

When our existence is threatened we are miserable!

If it is destroyed, we fall into the abyss!

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Frank Joyce - 02:14pm Mar 11, 1998 ET (#3789 of 3793)

Dawn:

If the birth proceeded normally then a lamb would have been born. This would have been recorded. All scientists who do animal research keep records of there animals. Here in CA you can get a hefty fine for not keepiong good records. Anyway if the brith took place normally as you say it would be very easy fro wilmut to track down the lamb and do as many genetic tests as possible to distinguish it from Dolly. That is quite a simple task. Even if teh sheep gave birth elsewhere the records kept by the breeders would still be sufficient to track down the missing lamb. This is not what Wilmut is doing. Instead he is trying to prove that dolly's cells are aging faster than normal.

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Bob Janitor - 03:05pm Mar 11, 1998 ET (#3790 of 3793)

A positive statement as to the involvement telomeres play in any role is purely speculative.

Tom, the role of telomers is well known. I don't think you can just dismiss them as speculative.

Carl, most cancer cells replentish telomers by switching on a gene that produces telomerase. It is possible to enable this in non-cancer cells. That's why the company that discovered the gene's stock price jumped 44% the next day.

V. Manu: Um, sure, whatever.

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Dawn Willis - 04:21pm Mar 11, 1998 ET (#3791 of 3793)

Cliff: Sorry my posts aren't very clear. The two scientists who questioned Wilmut are V. Sgaramella of the University of Calabria, Italy and Norton Zinder of Rockefeller University. They did not try to repeat the experiments, but they knew enough about fetal development to question the data. The DNA analysis that was presented only showed that Dolly was a Finn Dorset sheep and not a Blackface like the recipient. Since the donor ewe was pregnant, there was a slim possibility that a fetal cell was present. Reading Wilmut's response to Sgaramella and Zinder, it sounds as if the pregnant Finn Doirset ewe may have been killed at the time the tissue samples were taken. He says, "These cell cultures were not established for the purposes of nuclear transfer, but had been previously isolated for other studies. The reason that a pregnant donor ewe was prepared was to establish, in culture, a cell line that exhibited mammary epithelial-specific characteristics for long-term culture. This was part of a collaboration between PPL Therapeutics and the Hannah Research Instutute. For this reason, the genotypes of the fetus and the ram used for insemination were not analyzed, and no fetal material was retained for analysis."

Frank Joyce: It sounds as if record-keeping is not as thorough in Scotland as it is in CA. It appears that the mammary cells were intended to be the negative control.

Tom A and Carl N: Differentiated and specialized are not the same thing in the minds of developmental biologists.. I just sat in on a grant application peer review meeting of developmental biologists, and the ones I talked to define differentiated as having both specialized structure and function, plus either not dividing, or only able to divide into cells that lookand act just like them. No one considered a zygote to be a differentiated cell---although it is specialized. Cancer is often classified as well-differentiated (which has a good prognosis) or undifferentiated (poor prognosi

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Frank Joyce - 06:14pm Mar 11, 1998 ET (#3792 of 3793)

Zygote differentiated?

Not really the early protein sythesis in the zygote comes from stored maternal RNAs. Studies that proved this involved enucleating eggs to prove that no nuclear genes were turned on. Other studies include the use of Actinomycin d, a drug that inhibits RNA synthesis. Basically all protein syntesis in the zygote comes from stored RNAs and not nuclear genes.

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Frank Joyce - 06:20pm Mar 11, 1998 ET (#3793 of 3793)

Dawn:

Even if udder cells were a control the lamb would be easy to track down. Wilmut is not doing this. He is insead trying to prove his cells are aging. I don't hthink anyone would excise Udder tissue from a sheep close to birth. that seems a bit unethical. Especially since the lamb/s is expected to nurse. Good lab practice suggests keeping records of birth, death and disposal of research animals along with pedigree, especially when doing anything involving genetics.

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Noel Yap - 07:41pm Mar 11, 1998 ET (#3794 of 3802)

Frank Joyce: You must assume that before the 2nd or 3rd splitting there would be 2 divisions by the fetal cells becuase they would be ready to divide after teh previous split and finish another division before the next split.

Can we use consistent definitions for "split" and "divide?" Sometimes I can't tell when we're talking about cells dividing and halving the culture.

Frank Joyce: Again as noel states we are working with whole numbers not 3.96 cells.

Tom was the one who originally said this. However, we are also working with probabilities. A good model would satisfy both (somewhat contradictory) requirements.

Frank Joyce: If we do have several doublings before the first split we would at a minimum have four.and a 1/16th chance all would be deleted. 50% that at least two persist. and 3 other possibilities, any combination of 3 cells, any one cell remaining and a 1/16th chance that all remain.

As I've said before, the rate of splitting should be a variable in the model.

Frank Joyce: Then two rounds of one double one split, and a round of two doublings and one split. At each time we don't know how many cells would persist but if it did deviate from two the odds would still be far greater that either 3 or 1 would persist.

The rate of splitting is probably not an integral multiple of the rate of division.

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Noel Yap - 07:41pm Mar 11, 1998 ET (#3795 of 3802)

Frank Joyce: The real important thing to remember is how many doublings were made before the first division.

More generally, what's important is the rate of splitting.

Tom Anderson: It does not matter when you split it in respect to each individual cell so long as the relative growth rate for all of them is constant.

Yes, constant growth (and splitting) rates is a big assumption in our models. Gimme a couple of months and I should be able to model changing rates, too (specially if I'm given how (mathematically) these rates change.)

Tom Anderson: It really does not effect much considering the real limitation here is the probability of selecting a fetal cell in the original sample in the first place.

I now see your point. Even if at the end of all the splitting 100% of the culture were fetal cells, the entire probability would still depend on the chances of pulling a fetal cell to begin with (~2x10-7.)

Tom Anderson: my use of non-integers here simply reflects your growth rate figure and allows for some cells not to have finished dividing, or started again. This accounts for probabilities dependent on the fact that all cells do not stop dividing at the culture division and then restart again.

This is correct.

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Noel Yap - 07:41pm Mar 11, 1998 ET (#3796 of 3802)

Tom Anderson: Even if you were to say that a fetal cell were guaranteed to be selected if it were present in the sample, then there would still be less than a ten-millionth of a percent probability of that occurring.

Right (except I think it's less than a millionth.)

Cliff Beall: I think each of you guys would agree that regardless of any probability you might calculate, a verification that Dolly's cells are showing signs of abnormal aging would put to rest the "heresy" that Dolly was cloned from a fetal cell,

Perhaps. Do we absolutely know that cloning from a fetal cell wouldn't result in these symptoms?

Frank Joyce - 09:31pm Mar 5, 1998 ET (#3745 of 3747)

Tom:

Frank Joyce: It does matter because we are talking about cycling times. the cycling time is not reset after each split!!!! You treat the problem as if it were a linear rate like miles/distance and it is not.

It doesn't matter, Frank. To put it simply, let's say one fetal cell was in the culture in the beginning. Just before selecting a cell to clone, the rates of division and splitting allowed the fetal cells to populate 100% of the culture. The total probability that a fetal cell was selected is then 100% times the probability of having a fetal cell in the culture to begin with. This is, as Tom and (I think) Dawn have said, about 2 in 10000000.

Bob Janitor: I think Frank and Tom haven't desevered getting banned for what they've said, or will say based on the content of their past material.

I agree, although I would prefer zero ad hominems.

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Noel Yap - 07:42pm Mar 11, 1998 ET (#3797 of 3802)

Bob Janitor: They've both been quite objective, and I think the content of this board is far more intelligent than any other on CNN.

I completely agree.

Cliff Beall: After the Seed scare, I am surprised things are returning to normal so soon.

So am I.

Carl Nicolai: One way to handle risks is to have insurnce.

I agree.

Carl Nicolai: The insurance companies are experts at evaluating risks.

They are experts in evaluating known risks. The risks involved in cloning are unknown at the moment.

Carl Nicolai: BTW no insurance company will insure the safety of a necular reactor.

Although the risks for a nuclear reactor are known, the possible losses far outweigh any affordable premiums they can possibly charge.

Carl Nicolai: Cloning for reproduction has just become another political football.

Yes, it has.

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Noel Yap - 07:42pm Mar 11, 1998 ET (#3798 of 3802)

Tom Anderson: Ahh, finally, midterms are over!

Mine are jsut starting.

Tom Anderson: if there ever were an accident, there would be so many people making a claim against the power company that both the power company and insurance company could just declare bankrupsy.

Businesses go under the assumption of "going concern." This means they conduct business as if it had an infinite lifetime. Assuming future bancruptcy goes against the "going concern" assumption.

Tom Anderson: But, in the meantime, it is free money for the insurance company seeing as there has never been an unsafe reactor in the United States.

Three Mile Island. Brookhaven National Labs.

Tom Anderson: Anyway, isn't nuclear reactor safety insured by the Nuclear Regulatory Commission?

I'm not sure, but the NRC hasn't completely fulfilled their end of their contracts.

Cliff Beall: I would have to say that banning is a type of regulating.

I agree.

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Noel Yap - 07:43pm Mar 11, 1998 ET (#3799 of 3802)

Cliff Beall: I see no particular harm in the European ban, or, for that matter, the proposed American ban.

I agree with this, too. So long as cloning research in general can proceed, no major harm is done by banning human cloning now. Any ban can be overturned in the future when more is known about the technology.

Carl Nicolai: Since the code can be listed as a one dimensional array that codes for a three dimensional structure it could be looked at as a complex crypographic system that incorporates the other uses for coding.

I follow your coding and information theory thread. But I don't see how cryptography is an issue.

My guess is that most of genetic code is historical junk (ie introns.) This would mean that the genetic code can be compressed even more than it is now.

Carl Nicolai: I would like to know more about this.

So would I. I would also guess that the current compression scheme is fractal in nature.

David Bordelon: People died because alcohol and abortion was banned in this country.

People die now because alcohol and abortion are legal.

David Bordelon: You think the possibility of cloning is scary, try uncontrolled hidden lab cloning.

I agree with the gist of your post, though.