The iPS cells are normal skin cells reprogrammed to become like embryonic stem cells, so they are capable of becoming any body cell/tissue type. They are much simpler to produce, don't require endangering women by removing their eggs, and are not ethically problematic because they don't require the destruction of human embryos.
While some are saying that this new technique could lead to cloning, others question the underlying reasons for this criticism…
[article suggesting this shown below, followed by comments and reports clarifying this concern]
"Japanese scientist Yamanaka now says he fears method will be used to create human being with only one biological parent. The pioneer of the newest stem cell technique hailed as solving the ethical problems with embryonic stem cell research expressed his fears that scientists would use the method to create a human being with only one biological parent in an interview with The Telegraph on December 13. Shinya Yamanaka, a professor at Kyoto University and one of the two researchers who pioneered the "reprogramming" of human skin cells into stem cell replacements, said his breakthroughs could have dire implications for the rest of reproductive science.
"In theory our work means that you can generate germ cells (eggs and sperm), which could be very good news for the treatment of infertility," he said. "But what if somebody took those sperm and eggs from a single person and fertilized them? The result would be something very strange and dangerous. At this time there are no guidelines or rules that would prevent this."
"These things could be done somewhere by rogue scientists, but not in the UK where all research is strictly regulated," said Chris Shaw, a professor at King's College, London. "It is going to be immensely difficult to achieve fertilization and implantation in a woman."
A spokesman for the Human Fertilisation and Embryology Authority, the UK's regulator overseeing practice in fertility treatment and embryo research, said that it was "legally a grey area," relying on laws to be introduced next summer to ban the practice.
Ian Wilmut, a professor at Edinburgh University and the researcher who gave rise to Dolly, the first cloned sheep, was quoted as saying he's abandoning his cloning efforts to adopt the skin cell pluripotent approach.
"The work which was described from Japan of using a technique to change cells from a patient directly into stem cells without making an embryo has got so much more potential," Wilmut said, according to BBC News. "Even though it's only been described for the mouse, when we were considering which option to pursue, whether to clone or whether to copy the work in Japan, we decided to copy the work in Japan."
The research breakthroughs, announced in July and published in November, have been hailed by much of the pro-life movement as an alternative to the unethical use of human embryos in medical stem cell research. However, others are expressing concerns about where this will all lead given that many scientists involved in this work are known to not have any concerns about the ethical dimensions of destructive embryonic research or cloning.
James Thomson, a biologist and professor at the University of Wisconsin in Madison and the second scientist to develop the new skin cell pluripotent method, thinks that human embryo research should continue.
"What I hope will not happen is that everybody says, 'See? We don't have to do embryonic stem cell research now,'" Thomson said in an interview with MSNBC (http://cosmiclog.msnbc.msn.com/archive/2007/11/20/474428.aspx). "Just like Dolly was our inspiration to do the screening in the first place, we could not have successfully done the screening without the existence of human embryonic stem cells. The Japanese group, Dr. Yamanaka's group, used four genetic factors in mice. They had tried the same [mouse] embryonic stem cell culture with human material and it didn't work. Then they used human embryonic stem cell conditions that had been developed at my lab and other labs."
Thomson emphasized the reliance on human embryonic stem cells in the process of finding the new pluripotent skin cell method, and sees embryonic stem cell research as instrumental to further breakthroughs.
"In our research, we actually used human embryonic stem cells as part of the screening process," he said. "So the research itself on human embryonic stem cells led to the next finding about pluripotent cells."
Thomson said that he never believed cloning could be used to develop new therapies.
"Mainly, it's just hugely inefficient and terribly expensive," he said.
Thomson hopes that pluripotent cells could serve the purpose that cloning research did, but does not think that cloning research should be abandoned either.
"This may not be the end of the story," he said. "These pluripotent cells may not be perfectly like embryonic stem cells. We don't know yet. But I do think this is the path that people are going to follow now."
Previous Coverage: Ethical New Stem Cell Method Used to Cure Sickle Cell Anaemia in Mice
http://www.lifesite.net/ldn/2007/dec/07120707.html
Japanese Breakthrough Prompts Germany to Increase Adult Stem Cell Funding
http://www.lifesite.net/ldn/2007/nov/07112903.html
Japanese Team May Have Found Stem Cell "Holy Grail"
htp://www.lifesite.net/ldn/2007/jul/07072007.html ;
[18December2007, LifeSiteNews.com, John Connolly, London]
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Comments by David Prentice:
The possibility he mentions (germ cell production, single-parent children) is one proposed for any ES cell, and remember iPS are an "ES-type" cell.
Actually, there are a couple papers where they toy with the idea of making new eggs or sperm with adult stem cells…
But also, no matter the cell type, I don't think they're going to be successful, esp. with the ES types. This seems a pretty empty argument.
Some other thoughts:
One of the arguments has been that human ESC and embryos were *required* for study and directly led to the iPS cells. Yamanaka himself is the best counter to this.
Yamanaka has said he never used any human eggs, embryos, or ESC.
He has used MOUSE embryonic stem cells. He figured it out in mice, and then applied the SAME genes with human skin cells; and it worked.
He's also shown (10 days after the first announcement) that he could get the same result without the potential cancer gene (another of their complaints, that iPSC can cause cancer.)
BUT keep in mind that Yamanaka also has mouthed (probably to save face with colleagues) that some embryos (meaning human embryos) are necessary
, at least for now, for comparison. So if you see those comments raised, take with a grain of salt.
HERE is a great article with some interesting comments from Yamanaka about not using embryos:
Risk Taking Is in His Genes By MARTIN FACKLER NYTimes December 11,
2007
Scientist at Work | Shinya Yamanaka
http://www.nytimes.com/2007/12/11/science/11prof.html
There's also this one:
"Neither eggs nor embryos are necessary. I've never worked with either," says Shinya Yamanaka. The first installment of his research appeared a year ago — and was greeted with polite scepticism by his colleagues. At the time they were mesmerized by dreams of cloning embryos and dissecting them for their stem cells.
Michael Cook, Is therapeutic cloning obsolete?, Mercatornet, Saturday, 16 June 2007
http://www.mercatornet.com/articles/is_therapeutic_cloning_obsolete/
Fact sheet:
Induced Pluripotent Stem Cells (iPS cells)
Embryonic Stem Cells without Embryos or Eggs
WHAT SCIENTISTS HAVE DONE
Dr. James Thomson of U WI (first to grow human ESC) and Prof Shinya Yamanaka from Japan each have a high profile paper released Nov 20 (in Science & Cell).
Both show that embryonic-type stem cells can be produced directly from ordinary human cells, such as a skin cell, without first creating an embryo.
Prof Yamanaka published a second paper Nov 30 in Nature Biotechnology in which he achieved the same result with human and mouse cells by adding only 3 genes, omitting one gene (myc, an oncogene) that had cancer-causing potential.
Both groups used viruses to add the genes, another potential concern for cancer, but they are already working on refining the technique to eliminate use of viruses.
The "direct reprogramming" technique, first developed by Yamanaka in mice in 2006, involves adding 3-4 genetic factors to an ordinary cell, such as a skin cell. These "reprogram" or "dedifferentiate" the cell directly into an embryonic-type stem cell (called "iPS cells"–induced Pluripotent Stem cells.)
Dr. Rudolph Janisch published a study in Science on December 6th showing that mouse iPS cells were able to treat sickle cell anemia in mice. There was no indication of cancer formation after 12 weeks.
They DO NOT start with adult stem cells, and they DO NOT produce adult stem cells. They are not stem cells from destroyed human embryos. These are EMBRYONIC-type stem cells.
ETHICAL SIGNIFICANCE
The technique DOES appear to hold the ethical line: no embryos created or destroyed, no cloning, no eggs needed.
However, it still produces embryonic-type stem cells.
So, these will still have all the practical scientific problems that "original" embryonic stem cells have– tumor formation, problems with getting desired functional cells, and as yet no proof that they will make a transplant match.
These cells cannot form an embryo by themselves.
There has been some discussion about the reports that mice were produced from the mouse iPS cells. This is not forming an embryo directly from the cells, but by two techniques that are used to test the pluripotent ability of any ESC. The cell is either injected directly into an existing blastocyst-stage mouse embryo, or a tetraploid embryo is formed by combining the cell with other cells. The mouse embryo is then placed into the womb of a surrogate mouse mother, gestated, and the born mice are examined to see if the ESC or iPSC contributed to all tissues.
REACTION
Coupled with the announcement by Ian Wilmut (the "father of Dolly") that he is abandoning cloning as a method, in favor of Yamanaka's method to get embryonic stem cells directly, these are significant announcements.
Wilmut, Thomson, and Yamanaka should be CONGRATULATED on turning from questionable science that has produced no useable results, to focus on more promising scientific methods, easier, cheaper, and available for funding now, that also meet the ethical bar (though realistically, Wilmut & Thomson still have no problem with embryo destruction–they are doing this for the scientific advantage.)
These events indicate there is no need to destroy embryos, nor cloned embryos for research.
ADDITIONAL TALKING POINTS on iPS cells: http://stemcellresearch.org/statement/pptalkingpointsweb.pdf
Do we still need embryos and cloning? Answering Common Claims about iPSCs
http://stemcellresearch.org/commentary/answeringcommonclaims.htm
NEWS STORIES
Researchers Turn Skin Cells Into Stem Cells
By Gretchen Vogel ScienceNOW Daily News 20 November 2007
http://sciencenow.sciencemag.org/cgi/content/full/2007/1120/1
Researchers Create Stem Cells Without Destroying Embryos
By GAUTAM NAIK WSJ November 20, 2007 9:16 a.m.
http://online.wsj.com/article/SB119556606750999184.html?mod=hpp_us_whats_news
Scientists Bypass Need for Embryo to Get Stem Cells
By GINA KOLATA NYTimes November 21, 2007
http://www.nytimes.com/2007/11/21/science/21stem.html
REFINED TECHNIQUE
Woman's skin turned to embryo cells
Roger Highfield reports that the alternative to cloning continues to show promise; The Telegraph (London) 7:01pm GMT 30/11/2007
http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2007/11/30/scicells130.xml
A simpler recipe for human stem cells
Adult skin cells turned to pluripotent stem cells without a cancer-causing agent
David Cyranoski, Naturenews Published online 30 November 2007
http://www.nature.com/news/2007/071130/full/news.2007.219.html
Reprogrammed Skin Cells Strut Their Stuff
By Gretchen Vogel, ScienceNOW Daily News, 6 December 2007
http://sciencenow.sciencemag.org/cgi/content/full/2007/1206/2
OTHER COMMENTS REGARDING CLONING & iPSCs:
There seems to be some angst about the Boston Globe article and Melton indicating iPS cells are "dangerous", so Harvard is sticking with cloning.
Thoughts & quotes to correct this:
Responses to:
Caution urged in new method for stem cells; Harvard sticks to cloning
By Colin Nickerson Boston Globe Staff / December 17, 2007
http://www.boston.com/news/education/higher/articles/2007/12/17/caution_urged_in_new_method_for_stem_cells/
They use some viruses for gene therapy now, FDA approved.
But I'm not sure you want to go down that path of arguing about viruses.
Better to go this route:
NO embryonic stem cells are FDA approved at this point, because they ALL cause tumors.
-but the iPS have already shown that they can treat a disease in mice
-the iPS succeeded where cloning failed
-everyone (incl Melton) is confident that they can get iPS without viruses
SO, one might ask why they *really* want to continue cloning, given that it's already proven to be less efficient (a failed technique by comparison), much more expensive, and risks women's health by exploiting them for their eggs…do they really want treatments to help people's health, or do they really want cloning?
————
ALL embryonic stem cells share the potential for cancer, whether derived from IVF embryos, cloning, or by iPS.
Only adult stem cells have successfully treated patients, and without any tumor formation.
The point of iPS cells is that there are no ethical concerns with their derivation, and it is easier, cheaper, more efficient than using IVF embryos and cloning.
Since the iPS cells might render cloning and embryo-destructive research obsolete (and have actually done so), they have to attack it in some way to continue to justify more cloning.
Even the Boston Globe article points out that cloning has had no success so far.
But they still hold out the canard that ESC, esp. from cloning, offer the "best hope" for treatments. By ignoring adult stem cells and actual, current treatments, they can continue their facade. What the Globe story really points out is that they are becoming desperate, still wanting money for their experiments, so attacking the more successful research to drag it down to their level is the only way; they have to plant doubt in peoples' minds.
Specifically regarding the retroviruses, and the potential cancer gene, myc.
Below are some quotes from earlier stories, noting that it won't be long before the virus question is answered (I especially like the quotes from… Melton himself!)
They have to focus on the viruses now, because Yamanaka (10 days after the original announcement) showed that the Myc gene could be eliminated from the mix, using only 3 genes.
And don't forget that Jaenisch recently showed that he could succeed with a treatment in mice with iPS cells, where he had failed using cloning.
————-
"It should be made clear that this amazing breakthrough will not produce immediate cures," Grompe said. "The therapeutic potential of all human pluripotent stem cells, including those generated by direct reprogramming, remains uncertain." "The risk for cancer — a feature common to all pluripotent stem cells — is a major problem and this risk may be higher in these cells than in embryo-derived stem cells because the viral genes used for reprogramming remain present in the cell," Grompe said.
Human Embryonic Stem Cells — Without an Embryo By NIDHI THAREJA, M.D.
ABC News Medical Unit
http://abcnews.go.com/Health/story?id=3891547&page=1
—————-
The crucial next step, according to an article in Science magazine, is to find a way to switch on the genes that cause the skin cells to regress into stem cells rather than relying on the retrovirus to insert the genes.
"It's almost inconceivable at the pace this science is moving that we won't find a way to do this," stem cell researcher Douglas Melton of Harvard University told Science magazine.
Scientists transform human skin cells into stem cells
Mira Oberman
Agence France Presse — English
November 20, 2007 Tuesday 2:27 PM GMT
——————–
Although promising, both techniques share a downside. The retroviruses used to insert the genes could cause tumors in tissues grown from the cells. The crucial next step, everyone agrees, is to find a way to reprogram cells by switching on the genes rather than inserting new copies. The field is moving quickly toward that goal, says stem cell researcher Douglas Melton of Harvard University. "It is not hard to imagine a time when you could add small molecules that would tickle the same networks as these genes" and produce reprogrammed cells without genetic alterations, he says.
Researchers Turn Skin Cells Into Stem Cells By Gretchen Vogel
ScienceNOW Daily News 20 November 2007
http://sciencenow.sciencemag.org/cgi/content/full/2007/1120/1
———–
The reprogrammed cells, the scientists report, appear to behave exactly like human embryonic stem cells. "By any means we test them they are the same as embryonic stem cells," Dr. Thomson says.
But even the retrovirus drawback may be temporary, scientists say. Dr. Yamanaka and several other researchers are trying to get the same effect by adding chemicals or using more benign viruses to get the genes into cells. They say they are starting to see success.
It is only a matter of time until retroviruses are not needed, Dr. Melton predicted.
"Anyone who is going to suggest that this is just a side show and that it won't work is wrong," Dr. Melton said.
New Stem Cell Method Could Ease Ethical Concerns By GINA KOLATA
NYTimes November 21, 2007
http://www.nytimes.com/2007/11/21/science/21stem.html
————–
According to Dr. George Daley, director of the International Society for Stem Cell Research, "No one knows when, if ever, human stem cells will be placed into patients," but this breakthrough makes "stem cells as tools for research immediately valuable." Scientists will use these stem cells to study diseases in a petri dish. Drug research is another area where these new stem cells will have immediate application.
Gupta's CNN blog Wednesday, November 21, 2007
http://www.cnn.com/HEALTH/blogs/paging.dr.gupta/2007/11/new-stem-cells-what-they-could-mean-to.html
—————-
Thomson said he was surprised it didn't take longer to discover how to reprogram ordinary cells. The technique, he said, is so simple that "thousands of labs in the United States can do this, basically tomorrow."
In contrast, the cloning approach is so complex and expensive that many scientists say it couldn't be used routinely to supply stem cells for therapy.
Scientists should be able to find other ways to slip the genes into the skin cells, Thomson said. Other scientists suggest that a purely chemical treatment, not inserting genes at all, might be able to get the same result.
The cancer-risk problem should be solved quickly, maybe within a year or so, said Doug Melton, co-director of the Harvard Stem Cell Institute.
Before then, iPS cells could be used in lab studies to study the early roots of genetic disease or to screen drugs. But of course, it's anybody's guess when a useful treatment would result from that.
Even with the cancer problem solved for transplant uses, there's another big hurdle:
The whole idea of using embryonic stem cells or iPS cells for treating people with conditions like diabetes and Parkinson's disease via transplant is itself far from proven.
Scientists will need to learn how to turn iPS cells into the right kind of tissue, and how to use that tissue in a way that will treat a person's disease.
Such studies, in the lab, animals and finally people, will take years.
As far as that obstacle goes, Thomson said, the breakthrough announced this week changes nothing. "We have a lot of work to do."
Hurdles Remain After Stem Cell Advance
By MALCOLM R
ITTER The Associated Press
Wednesday, November 21, 2007; 5:29 PM
http://www.washingtonpost.com/wp-dyn/content/article/2007/11/21/AR2007112101808.html
——————–
Unlike cloning, "the wonderful thing about this approach is that it's easy. You're going to see lots and lots of labs give it a try," predicts Robert Blelloch, a stem cell biologist at the University of California, San Francisco, who recently published his own reprogramming experiments based on Dr. Yamanaka's breakthroughs.
Ian Wilmut, who cloned Dolly, has long been hoping to find a treatment for motor neuron disease in people by using the same technology he used in his original sheep experiment. The eventual goal was to create embryonic clones of such patients, derive fresh tissue from those clones, and then transplant that tissue back into the patients.
Now, he's so impressed with Dr. Yamanaka's successes, he's decided to abandon cloning and try reprogramming instead. "Cloning has had its impact," says Prof. Wilmut. "It seems we should all focus our efforts on reprogramming."
Advance in Stem-Cell Work Avoids Destroying Embryos By GAUTAM NAIK
WSJ November 21, 2007
http://online.wsj.com/article/SB119556606750999184.html
————–
Their enthusiasm notwithstanding, scientists warned that medical treatments are not immediately available. The new method uses genetically engineered viruses to transform adult cells into embryo-like ones, and those viruses can cause tumors. But the cells will be instantly useful for research — "to move a patient's disease into a petri dish," as Daley put it.
And some scientists predicted that, with the basic secret now in hand, it may be only months before virus-free methods for making the versatile cells are found.
Some of the hurdles to medical applications have already begun to be overcome. One of the genes that Yamanaka used, called c-myc, can initiate cancers, for example. But Thomson's recipe does not include c-myc, and in recent studies Yamanaka has succeeded with a three-gene cocktail that excludes c-myc.
More generally, retroviruses are a problem because they disrupt a cell's DNA in random locations, which can trigger tumor growth.
Both Thomson and Yamanaka said they are now testing methods that don't involve retroviruses.
Among them are adenoviruses and fatty bubbles called liposomes, which deliver genes to cells without harming DNA, or even direct-injecting the biochemicals that the added genes produce inside cells.
Scientists differed on how big a challenge it would be to transcend retroviruses, but several said they were not concerned. "I don't think it is a big hurdle," Jaenisch said.
Advance May End Stem Cell Debate, Labs Create a Stand-In Without Eggs, Embryos
By Rick Weiss Washington Post Staff Writer Wednesday,
November 21, 2007; A01
http://www.washingtonpost.com/wp-dyn/content/article/2007/11/20/AR2007112000546.html
——————
Melton said he was unsure how the institute's donors would react to the findings. At the time of the institute's founding, human embryonic research was "the most promising way forward," according to Melton.
"Now I would say the reprogramming of stem cells is equally promising," he said.
Embryo research stays in focus at Harvard By Clifford M Marks, Harvard
Crimson; SOURCE: Harvard University Wire November 29, 2007 Thursday
——————
A simpler recipe for human stem cells: Adult skin cells turned to pluripotent stem cells without a cancer-causing agent.
David Cyranoski Naturenews Published online 30 November 2007 | Nature |
doi:10.1038/news.2007.219
http://www.nature.com/news/2007/071130/full/news.2007.219.html
————–
"The correction of sickle cell anemia described in our experiments indicates that harnessing autologous iPS derived cells for therapeutic purposes recapitulates several of the promises offered previously by SCNT…"
Hannah J et al., Treatment of sickle cell anemia mouse model with iPS
cells generated from autologous skin, Scienceexpress published online 6
December 2007, doi: 10.1126/science.1152092
———–
"This demonstrates that IPS cells have the same potential for therapy as embryonic stem cells, without the ethical and practical issues raised in creating embryonic stem cells,* says Jaenisch.
Reprogrammed adult cells treat sickle-cell anemia in mice, published
14:10 EST, December 06, 2007, http://physorg.com/news116172622.html
————–
Townes says he and Jaenisch initially collaborated on a project that used nuclear transfer to make corrected stem cells, a process called therapeutic cloning. But the experiments failed, he says, because nuclear transfer was too inefficient to produce the needed cells. The iPS cell technique "is amazingly efficient," he says.
Gretchen Vogel, Reprogrammed Skin Cells Strut Their Stuff, ScienceNOW
Daily News, 6 December 2007