Stem Cell Wars

[THP]

Great article. Well worth reading.

http://worldnetdaily.com/news/article.asp?ARTICLE_ID=38633

[Jeff]

I must admit that I too have been surprised at times by all the advances in ASC that we never hear about. The US is supposed to be so far behind yet it seems like the majority of successes are all happening right here in the good ole USA. Too bad they are so underreported.

~See you at the SCIWire-used-to-be-paralyzed Reunion http://www.stopstart.fsnet.co.uk/smilie/wavey.gif ~

[Wise Young]

Jeff,

The suggestion by this journalist (Michael Fumento) that researchers are arguing amongst themselves on the merits of ESC and ASC "for money" is disengenouos and insulting. Perhaps the same claim could be made about his motivation for making this spurious claim that "scientist in stem-cell cover-up deliberately exxaggerate embryonic advances, ignore adult", i.e. that he is making this claim "mostly over money". Please understand that I am not making this claim. I am suggesting that his claim that scientists are doing it for money is as spurious a claim as that people are against embryonic stem cell research for money.

The concept that scientists are arguing for embryonic stem cell research because they will make more money from such research is simply not true. In fact, the smart thing for many scientists, and many scientists have already chosen this route, is to abandon embryonic stem cell research. Adult stem cell research is non- controversial, is more likely to be supported by Federal NIH funds and also pharmaceutical industry, and get approving nods from everybody. In contrast, anybody who engages in embryonic stem cell research is looked upon by some as a baby-killer.

Believe me, scientists like myself would not say that embryonic stem cell research is important unless it is truly important. I don't believe that the future lies in harvesting stem cells from embryos but nevertheless strongly support embryonic stem cell research. The accusation that we get money from advocating embryonic stem cell research is simply wrong. There is no or little money in embryonic stem cell research, either from the government, industry, or private sector. Believe, those scientists who advocate for such research are not doing it for money but out of scientific conviction.

Wise.

[Jeff Weeks]

Wise, I really appreciate your perspective.

The reason the author struck a chord with me is that I believe the political environment which favors funding of ASC actually favors the reporting of ESC. Polls continue to indicate that our media has a liberal bias. Reporting ASC success does not serve their purpose. Reporting about ESC is much more useful in promoting their agenda.

I read the article with a keen interest about reporting. I think you read the article from a few more angles than me. http://sci.rutgers.edu/forum/images/smilies/smile.gif

[Wise Young]

Jeff,

What is most distressing to me about this debate is that it is attempting to sow the seeds of distrust of scientists. The main thrust of this article is that monetary interests are motivating embryonic stem cell research. In contrast, I think that fascination that scientists have in stem cells is not monetary but rather scientific.

Let me put stem cell research in perspective. I have just spent a day with Irv Weissman and Evan Snyder, two leading stem cell biologists of our time. Hearing them speak gave me additional perspectives into the magnitude of the scientific problem that stem cell researchers are grappling with. The discovery of adult stem cells has thrown one of the major founding principles of biology into question: the concept of differentiation.

Biologists have long considered development to be a one-way street. The organism starts out as an ominopotent egg that, when fertilized with a sperm, starts on the road of differentiation. It first produces pluripotent stem cells which then further differentiate into epidermal, mesodermal, and endodermal layers. These layers further differentiate into the tissues and organs that we are familiar with, including our nervous system.

Until the mid-1990's, cancer was the only example of cells going backwards in differentiation. Dedifferention was considered to be pathological. Indeed, the very language used to describe developing and cancerous cells suggested a simplistic theory of differentiation that posits that stem cells are "primitive" and differentiated cells are more "specialized".

The first blow against this theory of differentiation was struck when Ian Wilmot and colleagues cloned Dolly the sheep. They were able to put the nucleus of a differentiated breast cell into an egg, fool the egg into thinking that it is an egg nucleus, and start developing. In short, they were able to de-differentiate the nucleus straight back to its most "primitive" state.

The second blow came with the discovery of adult stem cells. The first such adult stem cells were described (or at least the concept was popularized) in the brain. Called neural stem cells, these cells raised a ruckus in neuroscience because it challenged a long-held theory that no new neurons are born in the brains of adults.

The third blow to the differentiation theory came in 1999 when Angelo Vescovi reported that neural stem cells can be transplanted into bone marrow and produce blood cells (see Turning brain into blood (http://news.bbc.co.uk/1/hi/sci/tech/259962.stm)).

The fourth blow came in 2000, when Ira Black and colleagues found that bone marrow stem cells can produce neurons in culture (see Researcher grow brain stem cells from bone marrow stem cells (http://www.cnn.com/2000/HEALTH/08/15/brain.stemcell/). This year, Black, et al. reported that bone marrow mesenchymal stem cells can produce all types of neural cells (seeMarrow stem cell transplants succeed (http://www.detnews.com/2004/health/0405/15/a02-152019.htm)).

In many ways, these discoveries spell the demise of the long-held theory of differentiation. It is a true revolution in biology. In my opinion, it ranks in the same category of scientific discovery as the overturning of Newtonian physics in the early half of the 20th Century, that eventually led to the development of nuclear power. The stem cell debate should be put into this context.

The limitation that President Bush and others have placed on embryonic stem cell research would be comparable to limiting nuclear physics research in the 1950's. The discovery that somatic cell nuclear transfer (SCNT) can be used to clone a mammal is as momentous as the first demonstration of nuclear fission. It was of course a theoretical possibility for many years before but Dolly was similar to the first nuclear explosion.

The current research on stem cells (adult and embryonic) is similar to nuclear physics of the 1950's when it was clear that nuclear energy would transform the world. President Bush's restriction of NIH funding of embryonic stem cell research would be like President Eisenhower restricting funding of nuclear physics research in the 1950's. Of course, Einsenhower did not restrict nuclear physics. If he had done so, the world would have been very different.

At stake is not just stem cell therapies but the very foundations of biology. What we find out about stem cells will provide the bases for understanding development, differentiation, and cancer. The textbooks of biology are being rewritten to accomodate this revolution and American scientists are being held back in this crucial area of research.

Wise.

[This message was edited by Wise Young on 05-26-04 at 05:30 AM.]

[NoDecafPlz]

Great!

Thanks Doc!

Joe.

[Faye]

Originally posted by Wise Young:


What is most distressing to me about this debate is that it is attempting to sow the seeds of distrust of scientists. The main thrust of this article is that monetary interests are motivating embryonic stem cell research. In contrast, I think that fascination that scientists have in stem cells is not monetary but rather scientific.

Let me put stem cell research in perspective. I have just spent a day with Irv Weissman and Evan Snyder, two leading stem cell biologists of our time.......... It is a true revolution in biology. In my opinion, it ranks in the same category of scientific discovery as the overturning of Newtonian physics in the early half of the 20th Century, that eventually led to the development of nuclear power. The stem cell debate should be put into this context.

The limitation that President Bush and others have placed on embryonic stem cell research would be comparable to limiting nuclear physics research in the 1950's. The discovery that somatic cell nuclear transfer (SCNT) can be used to clone a mammal is as momentous as the first demonstration of nuclear fission. It was of course a theoretical possibility for many years before but Dolly was similar to the first nuclear explosion.

The current research on stem cells (adult and embryonic) is similar to nuclear physics of the 1950's when it was clear that nuclear energy would transform the world. President Bush's restriction of NIH funding of embryonic stem cell research would be like President Eisenhower restricting funding of nuclear physics research in the 1950's. Of course, Einsenhower did not restrict nuclear physics. If he had done so, the world would have been very different.

At stake is not just stem cell therapies but the very foundations of biology. What we find out about stem cells will provide the bases for understanding development, differentiation, and cancer. The textbooks of biology are being rewritten to accomodate this revolution and American scientists are being held back in this crucial area of research.

Wise.



Thank you Dr. Young, for putting the Stem Cell Research situation in perspective in such a powerful way. http://sci.rutgers.edu/forum/images/smilies/smile.gif

BTW, for those of you who also want to meet Dr. Irv Weissman: he will be speaking at the First International Stem Cell Action Conference, June 5th, at UC Berkeley.
www.stemcellaction.org (http://www.stemcellaction.org)

Hope to see many of the California CC members there!!! http://sci.rutgers.edu/forum/images/smilies/cool.gif

"I do not believe that the same God who has endowed us with sense, reason, and intellect has intended us to forgo their use."
- Galileo Galilei

[Steven Edwards]

Originally posted by Wise Young:

Jeff,

Let me put stem cell research in perspective. I have just spent a day with Irv Weissman and Evan Snyder, two leading stem cell biologists of our time. Hearing them speak gave me additional perspectives into the magnitude of the scientific problem that stem cell researchers are grappling with. The discovery of adult stem cells has thrown one of the major founding principles of biology into question: the concept of differentiation.

Biologists have long considered development to be a one-way street. The organism starts out as an ominopotent egg that, when fertilized with a sperm, starts on the road of differentiation. It first produces pluripotent stem cells which then further differentiate into epidermal, mesodermal, and endodermal layers. These layers further differentiate into the tissues and organs that we are familiar with, including our nervous system. I'm about to go to an appointment, so I haven't read all of this yet, but the belief that things could only go one way has always confused me. I'm glad that scientists are investigating the other possibilities now. http://sci.rutgers.edu/forum/images/smilies/smile.gif

Post more when I get back.

-Steven
[I]...dear kindly judge, your honour, my parents treat me rough, with all their marijuana, they won't give me a puff, they didn't wanna have me, but somehow I was had, leapin' lizards, that's why I'm so bad

[Wise Young]

Steven, the first evidence of de-differentiation was recently reprted in Science magazine (Stem Cells Toward Sperm Cells And Back Again: Experiments Reverse Cells' Developmental Course (http://www.sciencedaily.com/print.php?url=/releases/2004/05/040519071433.htm). This is in Drosophila (fruitfly). It seems that the germ cells (which are stem cells) that produce sperm not only reproduce themselves. Sperm cells that are no more than 2 differentiation steps away can go backwards to produce germ cells again. The question is whether this can be done with cells that are further down the line of differentiation and what genes are responsible.

Because of the attitude that stem cells are more "primitive" than the differentiated cells that they produce, most scientists thought that it is the gene expression of the specialized cells that make them specialized. But an alternative possibility is that stem cells are highly specialized cells, i.e. cells that are highly specialized to produce other kinds of cells. This alternative makes sense if one thinks about it.

The egg is actually a very specialized cell, a cell that has certain receptors for sperm and can undergo a transformation when activated by sperm to produce stem cells that in turn produce the whole organism. Being an egg is not the "default" state of a cell. If being an egg or sperm is the "default" state of a cell, one would find eggs or sperm popping up all over the body. This of course does not happen. Therefore, it is reasonable to postulate that an egg is a highly specialized cell and, likewise, stem cells are high specialized cells.

I also want to point out that true stem cells do not themselves differentiate, in the sense that they become the cells that they produce. Rather, they produce another type of cell while remaining stem cell-like. Also, the definition of a stem cell is a cell that can produce more of itself. That is actually the main difference between embryonic stem cells and adult stem cells. Adult stem cells do not remain stem cells in culture for long. They tend to differentiate over time and stop becoming stem cells. However, embryonic stem cells, as long as they are grown in a condition that has certain growth factors, will remain stem cells indefinitely and will produce more stem cells.

In the Drosophila study cited above, it appears that stem cells emit a "chemical signal" that tells other cells around them to retain their "stemness". There are other studies that suggest that a single RNA message tells the stem cell to remain stem cells while the offspring cells become differentiated.

Wise.

[DA]

Originally posted by Jeff:

I must admit that I too have been surprised at times by all the advances in ASC that we never hear about. The US is supposed to be so far behind yet it seems like the majority of successes are all happening right here in the good ole USA. Too bad they are so underreported.

~See you at the SCIWire-used-to-be-paralyzed Reunion http://www.stopstart.fsnet.co.uk/smilie/wavey.gif ~
exactly. the usa isnt lagging behind. we are in the pack, slightly ahead. we could have been farther ahead. its amazing how little cc members know about asc.

[Steven Edwards]

Oh how I crave to be in a research lab and direct research. And to think, I hated Biology in 9th grade because I disagreed with so much of what was in the books. http://sci.rutgers.edu/forum/images/smilies/smile.gif

I have a strong feeling that with the correct gene therapy techniques, any cell in the human body can be turned into any other type of cell, including those that produce germ cells. In normal development, I can see how "differentiation" can be assumed, but once genes were discovered [and the fact that genes coded for proteins, which can help control gene expression], I think the concept of differentiation should have been reinvestigated. Oh well, gotta love us armchair quarterbacks. http://sci.rutgers.edu/forum/images/smilies/wink.gif

Just to throw this out -- regarding ASC vs ESC -- I have a few ideas on how ESCs remain stem cells. A recent study [released Monday] (http://www.sciencedaily.com/releases/2004/05/040521070635.htm) showed that some mRNAs are destroyed while the ribosomes are reading them to produce proteins. In a similar fashion, I believe it could be possible that when ESCs produce differentiated cells, those differentiated cells -- in addition to their normal functions -- produce the "supporting factors" that help ESCs retain their stemness. Through the generations, the children then begin producing factors that stop their parents' ability to produce the appropriate "stemness" supporting factors. In essence, the kids -- not the fellow stem cells -- determine when to cut off life support for their grand-[grand-grand]-parents.

That's the idea of mine that I think holds the highest likelihood of being near the mark.

-Steven
...dear kindly judge, your honour, my parents treat me rough, with all their marijuana, they won't give me a puff, they didn't wanna have me, but somehow I was had, leapin' lizards, that's why I'm so bad

[Wise Young]

Steven,

The mechanisms that prevent de-differentiation are remarkably effective. By the way, I believe that it must be a simple mechanism in order to be so robust. It is no accident that almost no examples of de-differentiation have been found in all these years of biological research. Let me give you an example. If the stem cells in our nose suddenly started to make sperm, that would be considered the miracle, probably worthy of sainthood. But it just doesn't happen.

On the other hand, perhaps it is because we haven't looked hard enough. For example, perhaps one out of a thousand or ten thousand cells spontaneously revert to stem cells. If these stem cells just produce a few cells and then go away, we probably would not recognize it.

Wise.

[Steven Edwards]

I agree that the mechanism is effective and simple; the method I described below fits both requirements. It's hard to convert my programming oriented thoughts to words and make understandable correlaries, so I may have missed a thing or two. http://sci.rutgers.edu/forum/images/smilies/smile.gif

I may try a new description tomorrow after giving it some more thought. 30,000+ genes offers a *lot* of potential mechanisms, as you know. Have you given any thought to the mechanisms involved in how they retain their stemness?

-Steven
...dear kindly judge, your honour, my parents treat me rough, with all their marijuana, they won't give me a puff, they didn't wanna have me, but somehow I was had, leapin' lizards, that's why I'm so bad

[Faye]

Originally posted by Wise Young:


The mechanisms that prevent de-differentiation are remarkably effective.

Is a teratoma an example of where the mechanism breaks down?

"I do not believe that the same God who has endowed us with sense, reason, and intellect has intended us to forgo their use."
- Galileo Galilei

[Wise Young]

Faye, a teratoma is a stem cell tumor. Stem cells sometimes lose their growth control. Most teratomas are located along the path that germ cells migrate in the body and therefore may be a tumor of germ cells in many cases. Presumably it is just a stem cell that has grown out of control. By the way, teratomas are quite rare in humans, usually in children.

When I refer to dedifferentiation or trans-differentiation, I am thinking about stem cells in one tissue producing cells of another tissue. For example, it would be like the stem cells in your brain suddenly deciding that they will make hair cells or bone, or blood cells. Although these are not necessarily tumors, a general assumption when we see a type of tissue that should not be there, we don't think about dedifferentation but rather cancer.

Wise.