November 20, 2007
Skin Cells Reprogrammed Into Pluripotent Stem Cells

Adult human cells can be reprogrammed to act like embryonic stem cells (which are notable for their ability to become all other cell types in the body).

In a paper to be published Nov. 22 in the online edition of the journal Science, a team of University of Wisconsin-Madison researchers reports the genetic reprogramming of human skin cells to create cells indistinguishable from embryonic stem cells.

...

The new study was conducted in the laboratory of UW-Madison biologist James Thomson, the scientist who first coaxed stem cells from human embryos in 1998. It was led by Junying Yu of the Genome Center of Wisconsin and the Wisconsin National Primate Research Center.

For several years I've been expecting clever scientists to figure out ways to basically program around the limitations on embryonic stem cell research. By finding ways to turn the knobs on genetic switches in the cell it was inevitable that scientists would figure out how to make cells change state into embryonic cells. They will next find more genetic knobs to turn in order to convert embryonic cells into precisely desired cell types and they will even find ways convert between various non-embryonic cell types while totally avoiding an intermediate state where the cells are like embryonic cells. Cells are just complex state machines. The next few decades of advance in biotechnology can be seen as a series of advances in techniques for causing desired and useful cell state transitions.

Shinya Yamanaka of Kyoto University led a separate team that also accomplished this same goal of reprogramming adult skin cells to turn them into pluripotent stem cells

The same feat is reported in the journal Cell by Prof Yamanaka with colleagues in Japan and America, the scientist who pioneered this approach of "nuclear reprogramming" in mice. He too reports that a simple recipe turns human skin cells into embryonic stem cell-like cells, he calls "iPS" cells.

From about 50,000 human cells treated with four factors introduced by a virus, his team obtained 10 distinct kinds of embryonic like cells.

"This efficiency may sound very low," said Prof Yamanaka but in practice it means a single experiment in a Petri dish will yield several lines of embryo like cells, while cloning would require dozens of human eggs to achieve the same feat.

Each team introduced 4 genes into the nucleus to create this effect.

Doug Melton, a stem-cell researcher at Harvard University, heralded the breakthrough.

Yamanaka, of Kyoto University in Japan, last year was the first to reveal the successful creation of reprogrammed cells in mice; he and two other research groups published improvements on that step this July. Many scientists thought it would take years to do the same with human cells.

"We appear to be closer than we ever thought we might be to a day when we could use this alternative method," Melton said in prepared remarks.

Though Thomson and Yamanaka both reprogrammed human skin cells using four genes, their methods differed slightly. They used different viruses to deliver the genes. Both used genes called Oct4 and Sox2, but Thomson used two others called Nanog and Lin28, while Yamanaka used c-Myc and Klf4.

These results aren't surprising. The most important difference between embryonic cells and adult cells is whch genes are activated. These scientists basically figured out how to apply a software patch to human cells that made them express genes that make them act like embryonic cells. Scientists have already identified these genes as active in early stage embryonic stem cells and have experimented with activating them in mouse cells.

These results might not yet provide perfect substitutes for embryonic stem cells.

"While this is exciting basic research, it could still take years to get this to work in humans in a way that could be used clinically," said Robert Lanza, chief scientific officer of Advanced Cell Technology in Worcester, Mass. "I cannot overstate that this is early-stage research and that we should not abandon other areas of stem cell research."

It seems unlikely that these cells have been pushed into a state that is exactly like the state of an embryonic stem cell. That state might have very subtle aspects that are important in ways we have not yet discovered. The cells created by these two new methods might suffer lingering effects from the introduced genes and a technique to silence those genes at some later step might be needed. But then cloning didn't produce perfect embryonic stem cells either.

Christian opponents of embryonic stem cell research are celebrating this discovery since the result reduces the advantage of working with embryo-derived cells.

Today, Family Research Council President Tony Perkins praised the research of Dr. James Thomson and Dr. Shinya Yamanaka. Thomson, the first to grow human embryonic stem cells, and Yamanaka from Japan, published results in the journals Science and Cell, respectively, showing that embryonic-type stem cells can be produced directly from ordinary human skin cells, without first creating or destroying human embryos

Here's yet another group opposed to embryonic stem cell research who are hailing this result

Wesley J. Smith, the Discovery Institute's Senior Fellow in Bioethics and author of Consumer's Guide to a Brave New World, hailed the breakthrough as demonstrating that ethical science is also good science: "Everyone should applaud this tremendous scientific achievement. We now have the very real potential of developing thriving and robust stem cell medicine and scientific research sectors that will bridge, rather than exacerbate, our moral differences over the importance and meaning of human life."

They are happy about this result because it probably will make the use of embryonic stem cells unnecessary. But the result also seems to show that the difference between embryonic stem cells and other cells is just different settings on a few genetic switches in the cell. So doesn't this result make embryonic stem cells seem less magical and less supernatural?

Share |      Randall Parker, 2007 November 20 11:27 PM  Biotech Stem Cells


Comments
HellKaiserRyo said at November 20, 2007 11:54 PM:

Uh... I wonder if this eliminates eugenic genetic engineering since cloning cannot be done now.

Well, we still have embryo selection, which was advocated (instead of genetic engineering) by Richard Lynn in his book Eugenics.

Well, it probably doesn't really matter at all (genetic engineering of progeny) if cybernetic implants and stem cell rejuvenation for the brain are readily available. The challenge now is to make those accessable to all as it will eliminate poverty (where a sufficent infrastructure exists to dispense those technologies).

And regarding the proposals of engineering human nature; I will probably concede that it might not be a good idea to make humans extremely altruistic. I do think it would still be a good idea, and I most certainly do not want to live in a world where everyone is a good communist. I suppose increasing the mean of human altruism and empathy by a standard deviation or too (from the current human baseline) is satisfactory. We do not want the sterotypical antithesis of the Randian man. I suppose such minor adjustments would lower the gini index for nations too.

HellKaiserRyo said at November 21, 2007 12:05 AM:

"two" not "too", need intelligence enhancement too (use it correctly that time).

David Govett said at November 21, 2007 9:55 AM:

Even more remarkable is that these scientists transmuted skin cells into a Nobel Prize. Zounds!

Ben R. said at November 21, 2007 11:03 AM:

"They are happy about this result because it probably will make the use of embryonic stem cells unnecessary. But the result also seems to show that the difference between embryonic stem cells and other cells is just different settings on a few genetic switches in the cell. So doesn't this result make embryonic stem cells seem less magical and less supernatural?"

That would be applying logic to a worldview that is fundamentally irrational.

Brian H said at November 22, 2007 7:40 AM:

2 comments:
1) Since the silenced genes being re-introduced are known, it seems obvious that at some point it will be possible to un-silence the originals instead, thereby eliminating the viral invasion stage.
2) Pluripotent cells can be, if I'm not mistaken, turned into embryos since they are able to regen all tissue types; I suspect such a cell implanted in a suitable medium would become an embryo. But I may be wrong.

Fly said at November 22, 2007 4:30 PM:

"Pluripotent cells can be, if I'm not mistaken, turned into embryos since they are able to regen all tissue types;"

Totipotent cells are needed to make the placenta as well. But, yeah, I expect they could make totipotent stem cells with the same technique. Might be useful for animal cloning once the technology is perfected.

Marc said at November 26, 2007 11:01 AM:

"'They are happy about this result because it probably will make the use of embryonic stem cells unnecessary. But the result also seems to show that the difference between embryonic stem cells and other cells is just different settings on a few genetic switches in the cell. So doesn't this result make embryonic stem cells seem less magical and less supernatural?'"

"That would be applying logic to a worldview that is fundamentally irrational."

No, that would be deliberately misrepresenting the pro-life position. Pro-lifers are not opposed to embryonic stem cell research because they believe embryonic stem cells are magical and supernatural. Pro-lifers oppose embryonic stem cells because you have to destroy a human embryo to procure them, and pro-lifers believe that human embryos are human beings first, embryos second, in much the way that human infants, say, are human beings first, infants second. Thus, human embryos have the right to life under the Constitution which we can't simply brush aside for the purpose of scientific research.

Ben R. said at November 26, 2007 12:14 PM:

"Pro-lifers oppose embryonic stem cells because you have to destroy a human embryo to procure them, and pro-lifers believe that human embryos are human beings first, embryos second, in much the way that human infants, say, are human beings first, infants second."

How can one define human life by the composition of the blastocyst or the potential for it to become a full grown human? Modern techniques inevitably ensure any given cell can (or will be able to) mimic either characteristic. From a philosophical perspective, it would be more accurate to create a functional definition of what it is to be human and go from there, as opposed to look for the earliest potential for human life.

Marc said at November 26, 2007 5:34 PM:

"How can one define human life by the composition of the blastocyst or the potential for it to become a full grown human?"

Look, it's not that difficult a concept to grasp. Pro-lifers define a person as an individual member of the human species. In other words, if you're a homo sapien, you're in. Every homo sapien has a beginning and an end. We all began at conception and we all will end with our deaths. All the time one spends in between those two points, he or she is a person--again, an individual member of the human species. It doesn't matter how old you are. The fact that an embryo is an extremely young human being doesn't change the fact that she is a human being, any more than the fact that my aged great-grandmother is an extremely old human being changes the fact that she is a human being.

As for cloning, obviously, someone who was cloned will have a different origin point than conception (which never happened). I don't know enough about the mechanics of cloning to speculate on what that point will be. But science's burgeoning ability to manipulate cells doesn't change the fact that every individual alive today had his or her start at conception.

Ben R. said at November 29, 2007 11:11 AM:

"Every homo sapien has a beginning and an end. We all began at conception and we all will end with our deaths."

Why start with fertilization exactly? What is the objective standard for doing so? By what standard is a fertilized egg suddenly a person, genetic distinctiveness? Potential?

"As for cloning, obviously, someone who was cloned will have a different origin point than conception (which never happened). I don't know enough about the mechanics of cloning to speculate on what that point will be. But science's burgeoning ability to manipulate cells doesn't change the fact that every individual alive today had his or her start at conception."

But it is simply a matter of time before that isn't the case. Why retain a basic ethical stance that is unsustainable?

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