Posted on 11/20/2007 7:40:45 AM PST by Pyro7480
NEW YORK - Scientists have made ordinary human skin cells take on the chameleon-like powers of embryonic stem cells, a startling breakthrough that might someday deliver the medical payoffs of embryo cloning without the controversy.
Laboratory teams on two continents report success in a pair of landmark papers released Tuesday. It's a neck-and-neck finish to a race that made headlines five months ago, when scientists announced that the feat had been accomplished in mice.
The "direct reprogramming" technique avoids the swarm of ethical, political and practical obstacles that have stymied attempts to produce human stem cells by cloning embryos.
Scientists familiar with the work said scientific questions remain and that it's still important to pursue the cloning strategy, but that the new work is a major coup.
"This work represents a tremendous scientific milestone — the biological equivalent of the Wright Brothers' first airplane," said Dr. Robert Lanza, chief science officer of Advanced Cell Technology, which has been trying to extract stem cells from cloned human embryos.
"It's a bit like learning how to turn lead into gold," said Lanza, while cautioning that the work is far from providing medical payoffs.
"It's a huge deal," agreed Rudolf Jaenisch, a prominent stem cell scientist at the Whitehead Institute in Cambridge, Mass. "You have the proof of principle that you can do it."
There is a catch. At this point, the technique requires disrupting the DNA of the skin cells, which creates the potential for developing cancer. So it would be unacceptable for the most touted use of embryonic cells: creating transplant tissue that in theory could be used to treat diseases like diabetes, Parkinson's, and spinal cord injury.
But the DNA disruption is just a byproduct of the technique, and experts said they believe it can be avoided.
The new work is being published online by two journals, Cell and Science. The Cell paper is from a team led by Dr. Shinya Yamanaka of Kyoto University; the Science paper is from a team led by Junying Yu, working in the lab of in stem-cell pioneer James Thomson of the University of Wisconsin-Madison.
Both reported creating cells that behaved like stem cells in a series of lab tests.
Thomson, 48, made headlines in 1998 when he announced that his team had isolated human embryonic stem cells.
Yamanaka gained scientific notice in 2006 by reporting that direct reprogramming in mice had produced cells resembling embryonic stem cells, although with significant differences. In June, his group and two others announced they'd created mouse cells that were virtually indistinguishable from stem cells.
For the new work, the two men chose different cell types from a tissue supplier. Yamanaka reprogrammed skin cells from the face of an unidentified 36-year-old woman, and Thomson's team worked with foreskin cells from a newborn. Thomson, who was working his way from embryonic to fetal to adult cells, said he's still analyzing his results with adult cells.
Both labs did basically the same thing. Each used viruses to ferry four genes into the skin cells. These particular genes were known to turn other genes on and off, but just how they produced cells that mimic embryonic stem cells is a mystery.
"People didn't know it would be this easy," Thomson said. "Thousands of labs in the United States can do this, basically tomorrow."
The Wisconsin Alumni Research Foundation, which holds three patents for Thomson's work, is applying for patents involving his new research, a spokeswoman said. Two of the four genes he used were different from Yamanaka's recipe.
Scientists prize embryonic stem cells because they can turn into virtually any kind of cell in the body. The cloning approach — which has worked so far only in mice and monkeys — should be able to produce stem cells that genetically match the person who donates body cells for cloning.
That means tissue made from the cells should be transplantable into that person without fear of rejection. Scientists emphasize that any such payoff would be well in the future, and that the more immediate medical benefits would come from basic research in the lab.
In fact, many scientists say the cloning technique has proven too expensive and cumbersome in its current form to produce stem cells routinely for transplants.
The new work shows that the direct reprogramming technique can also produce versatile cells that are genetically matched to a person. But it avoids several problems that have bedeviled the cloning approach.
For one thing, it doesn't require a supply of unfertilized human eggs, which are hard to obtain for research and subjects the women donating them to a surgical procedure. Using eggs also raises the ethical questions of whether women should be paid for them.
In cloning, those eggs are used to make embryos from which stem cells are harvested. But that destroys the embryos, which has led to political opposition from President Bush, the Roman Catholic church and others.
Those were "show-stopping ethical problems," said Laurie Zoloth, director of Northwestern University's Center for Bioethics, Science and Society.
The new work, she said, "redefines the ethical terrain."
Richard Doerflinger, deputy director of pro-life activities for the U.S. Conference of Catholic Bishops, called the new work "a very significant breakthrough in finding morally unproblematic alternatives to cloning. ... I think this is something that would be readily acceptable to Catholics."
Another advantage of direct reprogramming is that it would qualify for federal research funding, unlike projects that seek to extract stem cells from human embryos, noted Doug Melton, co-director of the Harvard Stem Cell Institute.
Still, scientific questions remain about the cells produced by direct reprogramming, called "iPS" cells. One is how the cells compare to embryonic stem cells in their behavior and potential. Yamanaka said his work detected differences in gene activity.
If they're different, iPS cells might prove better for some scientific uses and cloned stem cells preferable for other uses. Scientists want to study the roots of genetic disease and screen potential drug treatments in their laboratories, for example.
Scottish researcher Ian Wilmut, famous for his role in cloning Dolly the sheep a decade ago, told London's Daily Telegraph that he is giving up the cloning approach to produce stem cells and plans to pursue direct reprogramming instead.
Other scientists said it's too early for the field to follow Wilmut's lead. Cloning embryos to produce stem cells remains too valuable as a research tool, Jaenisch said.
Dr. George Daley of the Harvard institute, who said his own lab has also achieved direct reprogramming of human cells, said it's not clear how long it will take to get around the cancer risk problem. Nor is it clear just how direct reprogramming works, or whether that approach mimics what happens in cloning, he noted.
So the cloning approach still has much to offer, he said.
Daley, who's president of the International Society for Stem Cell Research, said his lab is pursuing both strategies.
"We'll see, ultimately, which one works and which one is more practical."
It would be interesting to see if this research was funded by the government or the public sector.
If you read the article, there are no ova involved. No ovum means no embryo, as far as moralists are concerned.
All they're doing is "de-programming" the skin cells so they can become something else.
As long as there's money to be made, you bet.
The whole point of this announced breakthrough is that they believe they have gotten these cells to have all the qualities of embryonic stem cells. I.e. they are totipotent; can be turned into any and all types of cells. For use in treatments, they would interfere with the cells’ development to steer them into becoming only certain types of cells or a certain organ, but without such steering they would develop into a complete embryo. If they can’t develop into a complete embryo, then they are also limited in what types of cells/organs they can be steered to develop into.
The problem with “adult” stem cells is that they cannot be turned into any and all types of cells needed — certain adult stem cells can be turned into a limited number of cell types, but they have all gone too far down the path of the differentiation to be turned into other cell types. What these researchers claim to have done is to have taken an adult cell and engineered it back to the embryonic state, from which it CAN develop into all cell types. They seem unsure as to whether they have really gotten 100% of the way there, but they know they need to get 100% of the way there in order for their technique to be really useful for what they’re hoping it will be useful for.
The tumor problem is over-hyped (and not entirely limited embryonic cells), but it will be solved in due course like all the other challenges.
"All" they are doing is de-programming the skin cells so they can become EVERYTHING else. When the moralists figure out that everything includes whole babies (and believe me, it won't be long) any of them who have been focused on ova involvement will become unfocused very quickly. The only test for whether these researchers have accomplished what they think they have, is to see if the cells can be developed into normal embryos. This will of course be done with animal studies at first, but as soon as it's successful in animals, human reproductive cloning will follow quickly.
If what they have is a 100% totipotent cell, what they have is a Day 1 embryo. There’s no advantage here over using IVF embryos -— except that they won’t have to hyperovulate females to get more “raw material”: for which I will give a quarter of a hooray.
Had W never stood up to the political pressure from the pro-aborts, this would never have come to pass.
I suspect nothing will change in California regarding the move to provide ever more funding to embryonic stem cell “research.” It never really was about research, medicine or curing disease, and I’m sure you know what I mean. It was as firmly rooted in science as global warming. This embryonic obsession was always a way of obtaining through the back door a source of public funding of abortion. It will continue as planned.
Well, there’s a big advantage in that they can produce genetically matched cells, and thus treatments that don’t require the patient to take anti-rejection drugs (which don’t always work) for the rest of their lives. THAT is what they’re so excited about, and with good reason.
The actual research was done in Japan, without gov’t cash from Japan. The guy who did the research actually took this route because he did not have funds to follow everyone else in the embryonic stem cell race. Is a very interesting story.
I am quite confused by what you are saying. Deprogramming skin cells doesn’t result in an embryo, it results in stem cells that mimic embryonic stem cells. These cells are valuable because they can become any other kind of stem cell, with the exception of germ cells. Without germ cells, how on earth do you think a baby is going to be created?
Even in this era of scientific research and test tube babies, reproduction still requires an egg. Without it, there is no way an embryo can be created. If you know otherwise, please explain to me how this is accomplished.
“If what they have is a 100% totipotent cell, what they have is a Day 1 embryo”
A fertilized egg is considered totipotent, meaning that its potential is total; it gives rise to all the different types of cells in the body. You are right in your understanding of the word totipotent, but there is no way to obtain totally totipotent cells without an embryo.
The cells that are being created here must be pluripotent, meaning they can create any kind of cell in the body, except those that create a fetus. An egg is still necessary to create an embryo or a fetus, and God help us if that ever changes.
I think they're on the verge of doing just that. Have you been keeping up with the UK's Human Fertilisation and Embryology Authority (I was going to say Orwellian-sounding, but no, I guess it's Huxleyan)? They are doing really freaky things with laboratory-based human reproduction. I think the idea now is to develop an "entity" which is just abnormal enough that it wouldn't be considered quite technically human. For experimental purposes.
Not that it matters. They don't seem to grasp the ethical objections to manipulating nascent humans. And the legal "barriers" are made of cobwebs. Thee are no meaningful limits at all.
A totipotent cell with a full set of non-defective DNA, that is dividing, can and will become a full fledged organism if put in the right environment (think uterus). This is why you can split an embryo in two and get two babies. Eggs have been a convenient environment in which to let nature do the work of de-programming the DNA of a differentiated cell nucleus, so that the DNA in that nucleus will acquire the ability to develop into a full organism (e.g. Dolly, the famous sheep). When the DNA has already been de-programmed back into a totipotent state, the egg is not needed.
And I don’t know why you think that a truly totipotent stem cell can’t differentiate into germ cells. Where do you think germ cells come from? The science of artificial gamete production, starting with adult somatic cells, is actually pretty far along already.
According to a recent news article in the San Francisco Chronicle, Stanford University critics are now saying that the totipotent cells lines they're developing now (embryonic) " may not yield medical treatments for decades, if ever."
"These companies are essentially taking advantage of people's ignorance and fears to make a buck," said David Magnus, director of the Stanford Center for Biomedical Ethics---"
Meanwhile, according to the Sacramento Bee, the umbilical cord cells have a splendid therapeutic potential precisely because they don't involve so many genetic markers and thus are potentially useful even for non-related recipients. Supposedly you just have to have about 200 cell lines available to provide a workable match for anybody in the state of California.
I wasn’t familiar with the organization, but I went to the web site and did some reading. The only thing that I could find was cytoplasmic hybrid embryos, which are part human and part something else. As reprehensible as that is, it still requires an egg.
As far as I know, There is still no way to create an embryo without an egg. (I am close to 100% sure about this) If there is no embryo, then life is not being destroyed. This process sounds like it has tremendous potential, and I am encouraged by the attention it is generating. Basically, these stem cells are as beneficial as they can be, without being true embryonic stem cells. Nothing is really lost, because the benefit of embryonic stem cells has nothing to do with them coming from an embryo.
Not all embryonic stem cells are totipotent, fool. Only prior to differentiation into placenta and inner cell mass are embryonic stem cells totipotent. Once differentiation starts, the differing cell lines are being built and these are pluripotent. Your anti-god, anti-life smarminess is spittling forth . Just shut up and read the entite article instead of trying to start an argument to promote your godless idiocies.
Ah.... what am I getting at? It becomes hard to draw a line between a human zygote and a zygote deliberately damaged or altered to be so abnormal that we call it something else.
The more permutations and combinations they make of different nuclear, cytoplasmic, and mitochondrial materials, the more the distinction between a human being, an animal, and a gobbet of lab material is blown to smithereens.
One would think somebody would see that in itself as an ethical problem.
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