Stem cell pioneer does a reality check

[Rollin Rick]

<A HREF="http://msnbc.msn.com/id/8303756/" TARGET=_blank>In
teresting read here</A> this has me thinking. Comments anyone?

[sbdspray]

That's great! The stem cell pioneer is giving opponents a free gift. Kill embryos for merely research, with no reasonable expectation for transplantation therapies in the decades to come. If that's the case, I agree with the opponents because if Dr. Thomson is interested in learning more about the human body for deeper and deeper research, then he has plenty with what cells he already has. Why should taxpayers pay for something that isn't aimed at their best interests. Yeah, maybe 50 years from now it will be, but if that's the case, they have plenty already at the rate they are going. I agree, the subject is stale, and I think people really have lost interest, and with public statements like Dr. Thomson's here, it's more likely to put someone to sleep. You eliminate the neccesity for cures, you've lost the majority of your audience. It looks as if Dr. Thomson and Leon Kass are little buddies, with the Madison-Chicago thing goin' on. I frankly couldn't care less about the issue anymore, it's clearly apparent that actual application of therapies in a clinical setting are beyond our realm of slim, fragile hopes.

sherman brayton

[Schmeky]

Brayton,

While Dr. Thomson doesn't believe ESC's will be used in a therapeutic/regenerative human setting, Korea and Geron are establishing stem cell banks for human application.

Thomson is entitled to his opinion, but the facts are self-evident. hESC's are going to be applied to humans, soon. Geron for acute SCI in 2006 and Korea for chronic SCI in the near future. These are irrefutable facts.

You constantly bitch about fragile hope and slim chances for application of therapies, well, it's is going to happen, and soon. What you should be concerned with is how well these real world hESC's are going to work in humans.

If they do, things will move very quickly. If they don't, you're right.

[sbdspray]

God..I hope you're right! inevitably, chronic complete SCI will be too much for modern medicine to address. It's like Dr. Young said some time back, it's like putting a squashed strawberry back together. What about severing the lower half of paraplegic's bodies and replacing them with robotics. That seems far more doable. Does anyone have burning neuropathic pain that's getting worse year by year? if so, what drug(s) are you on?

sherman brayton

[Schmeky]

Brayton,

No one knows about about reversing chronic SCI, it obviously hasn't been accomplished yet.

What you should be happy about is the fact that some of the most cutting edge research on the planet at reversing SCI is headed your way. It's a hot area of research worldwide in many countries.

I hurt all the time too. It suks. I'm a lot older than you, I have a very narrow window of opportunity; your window is much larger. You have the money for treatment. You have your arms, hands, and upper body; many don't. Dr. Young has even told you you're fixable.

Chill a bit

[sbdspray]

but schmeky, it's not about money! A million bucks ain't gonna get you out of this horrid mess. No disrespect to you whatsoever, at least you had more years of sex than I did, damn I was a late bloomer, and just getting started. I'd get hard, and desperetly try to hide it to no avail if I swept by an attractive, buxom woman. Now, I could be inside Pamela Anderson, and limp as a dead horse. I once foolishly thought it was just a question of building a bridge and reconnecting the pathways, now we know there are genes involved, chemical signals, thousands of spider web accurate connections to be made, it's just so utterly depressing and relentlessly grim, but hey, the miami project thinks it may be here in 5years.

sherman brayton

[Schmeky]

Brayton,

No disrespect taken on my end whatsoever. You're right, I did have more years, but, it was not enough.

I have picked up on your sexual frustration and believe me, it is justified. You have every reason to be bitter. The loss of sexual function in a young man is traumatic. Very traumatic. Throw in neuropathic pain, medical incompetence, and you have all the ingredients for anger and bitterness.

Do you remember a recent post where the famous SCI researcher Martin Schwab said the most fascinating thing he has seen in his 20 years of lab work was how the axons knew how to make the right connections once regeneration was initiated?

Don't loose all hope. You might get that little pecker of yours workin' one day afer all

Maybe mine too

[Steven Edwards]

Even though Dr. Thomson has said some things that people may not like, he has listed a number of important points that would be good to focus on in our advocacy. In my opinion, some of the more important ones:

Q: The people who use nuclear transfer generally say that the technique is optimized for producing the stem cells rather than making babies. They would not want to equate this with the process that produces embryos that were fit for implantation, and they'd argue that they're using the reproductive process differently ...

A: See, you're trying to define it away, and it doesn't work. If you create an embryo by nuclear transfer, and you give it to somebody who didn't know where it came from, there would be no test you could do on that embryo to say where it came from. It is what it is.

It's true that they have a much lower probability of giving rise to a child. ... But by any reasonable definition, at least at some frequency, you're creating an embryo. If you try to define it away, you're being disingenuous.

Q: What are some of those guesses about other technologies?

A: Well, if you take a nucleus and you put it into an oocyte [egg cell], the oocyte knows how to reprogram things. That's a problem that we can study, to understand how that happens. We don't really have a lot of information about how that works, so it's hard to predict how long it's going to take to solve that problem. I'd be surprised if within 10 years we didn't have another way to solve the problem, but it could be that it's a very, very hard problem and it's going to take a long time to do it.

Q: To find a way for a normal cell to reprogram itself?

A: Right. The message of Dolly is less about cloning, that we can clone Dolly or we can clone people or even do nuclear transfer to make embryonic stem cells; it's that the differentiated state is in principle reversible. And while that was known for a lot of model organisms, and there was even some evidence for that in mammals, Dolly really drove the message home that it was simply a question of time before we understood how to do that.

Prior to Dolly, we thought it was just impossible, we thought biologically it was not a reversible process. So Dolly does have implications for cloning animals and people, but really the biological message of Dolly is that the differentiated state is reversible under some conditions. ...

Regarding Geron's proposed therapy, it's important to note that they are not transplanting embryonic stem cells. Rather, they are using them as a tool to produce oligodendrocyte precursors, which are then transplanted.

MSNBC: Does it concern you that there are people who say, "We're this close to solving this sort of disease with stem cells, so let's pass this legislation"?

Thomson: Yeah, it's unfortunate. There are clearly exceptions on both sides, but most of the people who oppose this research, and most of the people who support this research, do it with a profound amount of misinformation. It'd be very nice to clear up that information as much as possible. You can still make an informed choice and be for it or against it, but at least it'd be based on the real facts.

An excerpt from one response:

So Dolly came along, and that did change the moral argument in ways that people haven't fully appreciated. The bottom line is that any cell in your body has a latent potential to form a human being.

An important corollary of this statement is that any cell in your body has a latent potential to become any other.

That's it from me for now.

-Steven
...got a little secret, I ain't gonna tell

[Wise Young]

Steven, thanks very much for highlighting the questions and answers. I spoke to Jamie Thomson at the San Francisco meeting. He is a very thoughtful man.

I agree with much of what he says. The main scientific implication of Dolly is not that we can clone an organism but the fact that differentiation is reversible. In fact, cloning of an organism occurs all the time. Every cell, when it undergoes mitosis, is cloning itself. An identical twin is a clone. The act of reproduction is in a form of cloning but, in order to increase genetic diversity, we have sexual reproduction so that offsprings would have different mixing off genes. It is a cloning-melding of two individuals.

Why is the discovery of dedifferentiation so important? First, differentiation is normally so tightly regulated that we believed that dedifferentiation was impossible. Woo-suk Hwang has shown that dedifferentiaion is not only possible in humans but can be reliably and efficiently carried out.

Gerry Schatten, who works with Dr. Hwang, has a wonderful movie of the nuclear transfer process. It shows graphically how the nucleus is placed into an egg that has had its nucleus removed. Under the microscope, it looks almost like putting a marble into a plastic bag of jello. That jello (egg cytoplasm) did something to the nucleus so that it was fooled into producing stem cells. That is what the nuclear transfer process is all about.

I am not sure that I agree with Jamie Thomson regarding the difficulty of finding out the factors in egg cytoplasm that does this to nuclei. Something in egg cytoplasm is telling the nucleus to start making stem cells. It is clearly a robust mechanism. The difficult part was showing that it can be done. Now, it is a matter of analyzing the components of egg cytoplasm and systematically determining what protein or molecules are involved. It may be a lot simpler than we think.

In fact, the way of all science is that things are both simpler and more complex than we think. At the beginning, it always looks incredibly complex because we don't know what is going on. This was the way it was before Dolly. Then, when we discover the mechanism, it is usually simpler than we thought. But, as we study the phenomeon more, it always turns out to be more complex than we thought.

Let me use the example of Jamie Thomson's own discovery, that mouse feeder cells can support human embryonic stem cells. A lot of other types of cells did not seem to work and almost all human embryonic stem cells isolated since 1997 have been initially grown on mouse feeder cells or conditioned media from such cells. Thus, about a year ago, the problem seemed very difficult. Then, all of a sudden, it become clear that mouse feeder cells provide a factor called BMP-4 and that this factor inhibits differentiation of embryonic stem cells. This discovery allowed scientists to eliminate the mouse feeder cells http://www.sciencedaily.com/releases...0223141419.htm

Initially, it was thought that LIF (leukemia inhibiting factor) was the critical factor that prevented differentiation but Austin Smith showed BMP-4 induced the production of proteins called "inhibitors of differentiation" or ID proteins, that collaborate with LIF to prevent differentiation and also stimulate the stem cells to self-renew or make more of themselves. So, the current approach is to grown human embryonic stem cells in cultures containing LIF and BMP-4.

By the way, other factors have been shown now to work like BMP-4. For example, many TGF-beta1 family of cytokines and GDF (growth differentiation factor) have similar effects to BMP. It turns out that transcription factors called SMADs are the principle downstream regulators of BMPs. What are downstream regulators? These are factors that influence the effects of BMP-4. So, now it is getting more complex. LIF, BMP, SMADs, IDs (ID1, ID2, ID3), GDF, TGF-beta1, and others. http://www.signaling-gateway.org/upd...2/nrm1288.html

Notch is a protein that resides on the surface of stem cells. When Notch is activated, the stem cells tend to remain undifferentiated and make more stem cells. However, when it is turned off, the stem cells themselves begin to change into more mature cells that can no longer produce many different kinds of cells. http://www.landesbioscience.com/jour...bt.php?id=1574 And finally, Notch has been implicated in aging of cells http://www.liebertonline.com/doi/pdf...16804323105035

This is really good biology, the stuff that future biology textbooks will talk about.

Wise.

[MrSoul]

Sherman, you wrote:

It looks as if Dr. Thomson and Leon Kass are little buddies, with the Madison-Chicago thing goin' on.

Could you explain what you mean by that? Madison-Chicago? The significance escapes me, don't get it.