More excitement over genetically ‘pure’ iPS cell technique

Another fine piece of science – and a great read - released today US time, giving an even 'cleaner' method of obtaining perfectly-matched embryonic-type stem cells (iPS cells) without ever creating or destroying an embryo. Once again we see that the furphy used by lobbyist-scientists in South Australia to distort the cloning debate there - namely that iPS cells are dubious because of 'genetic manipulation / viral integration' - is shown to be spurious. iPS cells are genetically as pure and safe (or unsafe) as anything made from embryos, and have the overwhelming advantage of matching the actual patient.

 

Note the final paragraph of the report below, confirming yet again that iPS cells (from our own skin) are functionally indistinguishable from embryonic stem cells, yet have the major technical advantages of genetic/immune compatibility and lab simplicity (and no ethical stress).

 

Hence the obvious question: what justification remains for using embryos, and of course, what possible place for manufacturing embryos by cloning?

 

The relevant paragraph reads: "The scientists found that those reprogrammed embryonic-like cells (dubbed "protein-induced pluripotent stem cells" or "piPS cells") from fibroblasts behave indistinguishably from classic embryonic stem cells in their molecular and functional features, including differentiation into various cell types, such as beating cardiac muscle cells, neurons, and pancreatic cells."

 

Here is today's press statement of the iPS paper in Cell Stem Cell:

 

A major breakthrough in generating safer, therapeutic stem cells from adult cells: Scientists completely avoid problems of genetic manipulation by instead using chemical programming

Public release date: 23-Apr-2009 http://www.eurekalert.org/pub_releases/2009-04/sri-amb042209.php

 

"The new technique solves one of the most challenging safety hurdles associated with personalized stem cell-based medicine because for the first time it enables scientists to make stem cells in the laboratory from adult cells without genetically altering them. This discovery has the potential to spark the development of many new types of therapies for humans, for diseases that range from Type 1 diabetes to Parkinson's disease.

 

The study was published in an advance, online issue of the journal Cell Stem Cell on April 23, 2009.

 

"We are very excited about this breakthrough in generating embryonic-like cells from fibroblasts [cells that gives rise to connective tissue] without using any genetic material," says Scripps Research Associate Professor Sheng Ding, who led the research.

"Scientists have been dreaming about this for years."

 

Normally, cells develop from stem cells into a myriad of increasingly more specialized cell types during early development and throughout a lifetime. In humans and other mammals, these developmental events are irreversible. This means that when tissues are damaged or cells are lost, there is usually no source from which to replenish them. Having a source of the most primitive stem cells available would be useful in many medical situations because these cells are "pluripotent," having the ability to become any of the body's cell types-potentially providing doctors with the ability to repair damaged tissues throughout the body.

 

However bright this promise, the use of stem cells in medicine has faced many hurdles. One strategy has been to work towards a therapy where doctors could take a patient's own adult cells and "reprogram"

them into stem cells. This not only avoids potential ethical problems associated with the use of human embryonic stem cells, it also addresses concerns about compatibility and immune rejection that plague therapies such as organ transplantation.

 

A few years ago, a team of researchers in Japan made a breakthrough in this general approach by converting mouse skin cells into mouse stem cells. The Japanese team accomplished this remarkable transformation by inserting a set of four genes into these skin cells. While the study was a powerful proof-of-principle, the therapeutic potential of genetically reprogrammed cells is limited because of safety issues. One obvious problem is that the four required genes and their associated foreign DNA sequences permanently reside in the cells when transplanted. Moreover, the specific genes in question are problematic because, in living tissue, they are linked to the development of cancerous tumors.

 

Many scientists have been trying to find safer ways to generate stem cells from adult cells -- developing methods that require fewer genes, or techniques that can put genes in and then take them out. However, to date all of these have still harbored significant safety concerns due to the nature of the genetic manipulations. Ding and his team previously reported the discovery of drug-like small molecules to replace some of those genes, but have also hoped to go even further and find ways to reprogram adult cells into stem cells without using any genes or genetic manipulations at all.

 

The team of scientists accomplished this extraordinarily challenging feat by engineering and using recombinant proteins, that is proteins made from the recombination of fragments of DNA from different organisms. Many different recombinant proteins have been therapeutically and routinely used to treat human diseases. Instead of inserting the four genes into the cells they wanted to reprogram, the scientists added the purified engineered proteins and experimen ted with the chemically defined conditions without any genetic materials involved until they found the exact mix that allowed them to gradually reprogram the cells.

 

The scientists found that those reprogrammed embryonic-like cells (dubbed "protein-induced pluripotent stem cells" or "piPS cells") from fibroblasts behave indistinguishably from classic embryonic stem cells in their molecular and functional features, including differentiation into various cell types, such as beating cardiac muscle cells, neurons, and pancreatic cells." ENDS.

11 reasons why we no longer need Embryos for Stem Cell Science – neurobiology Prof

Excellent, brief, argument by a leading neuroscientist, as to why embryos (let alone cloned embryos) are no longer required for Stem Cell Science:

Link: http://www.stemcellresearch.org/commentary/answeringcommonclaims.htm

Does Research Really Need Human Embryos and Cloning?

by Dr. Maureen L. Condic

April 16^th 2009.

Neurobiologist Maureen L. Condic investigates 11 common arguments in favor of embryonic stem-cell research, and explains why science may not need the controversial technique, after all.

ESCs, iPS or ASCs for macular degeneration: a no-brainer.

Yes, you read it in The Australian, that "an (embryonic) stem cell therapy to cure the most common cause of blindness has been developed. Surgeons predict it will become a routine one-hour procedure that will be generally available within seven years."

 

To the experienced eye, this is clearly another calculated bubble of hype – but for sake of argument, let's pretend this speculation actually might come to pass 'within seven years'. Then, in order to gently deflate this – or any – ESC bubble, let us ask the two key questions that any reasonable person must always ask:

 

1. Why use embryonic stem cells (ESC) when you can use induced pluripotent stem cells (iPS)? We know the two types are indentical in their properties, but there is one huge clinical difference: iPS cells match the patient, and ESCs do not. ESCs are foreign cells from a foreign individual, and require immune suppressants even in animal studies, to prevent rejection – just like with an organ transplant. Which would you, the patient, prefer?
   
2. For that matter, why use either ESC or iPS when you can use adult stem cells (ASC)? We already have reports of the capacity of ASCs to generate the same retinal cells generated by ESCs in this 'breaking news'. Again, there is not one but TWO huge clinical differences. ASCs, like iPS cells, match the patient – but ESCs are foreign. Further, ASCs alone are free from the tumour risk inherent in ESC / iPS cells. Which type of cell would you, the patient, prefer to have in the back of your eye?
   

In one example of ASCs used to generate retinal photorececeptor cells – published in the journal Stem Cells last year – the principal researcher comments on both the immune-rejection and ethical advantages:

Dr. Ahmad's research team recently published its findings in the journal Stem Cells. Their findings demonstrated that corneal stem cells could be converted into photoreceptors, he said, which suggests that they also could be used for repairing retinal damage. "This gives us hope that we may be able to manipulate these cells to treat retinal degeneration and restore sight," he said. "By using a person's own Muller adult stem cells, problems associated with immune rejection as well as the controversy surrounding the use of embryonic stem cells would be eliminated."

 

No, even if reckless authorities in the UK were to approve this proposed ESC trial, and risk tumours and immune rejection in the delicate ocular tissues of volunteers, sensible 'customer demand' will have the final say. No reasonable person will prefer ESCs – with all their ethical ugliness and need for innume suppressant drugs – over the simple and clean technique of iPS. Further, this reasonable person would not let either ESCs or iPS cells within a metre of my retina, when I could use ASCs instead and have no concern over tumours.

 

And finally, only ASCs are on track to treat the other aspect of macular degeneration – abnormal blood vessels in the retina.

 

For example, see Nature journal in 2002 – reviewed here. The researchers comment:

"Abnormal angiogenesis is the cause of visual loss in age-related macular degeneration, where new blood vessels grow under the retina.In the ocular disease models, the (adult) stem cells differentiated into endothelial cells and proliferated, forming new blood vessels. This actually rescued and stabilized the retinal vessels when they would otherwise be degenerated."

 

Or peruse the full article in the Journal of Clinical Investigation, 2004:

"In this study we demonstrate that whenever a fraction of mouse or human adult bone marrow–derived stem cells rescues retinal blood vessels that would ordinarily completely degenerate, a dramatic neurotrophic rescue effect is also observed."

 

Memo: whenever a claim for ESC therapy is made, always ask the two question: Why not use iPS and get a perfect genetic match? Why not use ASC and avoid the tumour question?

 

Never forgetting the one question that overarches this whole debate: Why not get this good science in an ethically uncontentious way, using a method that dose not exploit human embryos?

 

First Oprah, now Al Gore… realism is breaking out all over

It has long been clear that smart private money is fleeing cloning and embryo experimentation in favour of iPS, while only dumb public money - as promised by Obama - will prop up that redundant science. In order, it seems, to prop up the cultural triumph over Bush and his obscurantist ilk.

 

Forgetting the inconvenient truth that it was Bush whose ethically-targeted funding made this magnificent iPS discovery possible, Al Gore, of hanging chad and Supreme court appeal fame, is now standing to profit from Bush's smart move. And all the best to him. But there has been no more satisfying demonstration of the true future of stem cell science than this week's announcement that the former vice-President is putting $20 million into the "hot area of 'induced pluripotent' stem cells."

 

"I think", says Gore, "this is one of those good news stories that comes along every once in a while… It's a very important breakthrough that is filled with promise and hope."

 

Journalists are intelligently stating the ethical, as well as scientific, advantage of iPS: "Human embryonic stem cells are controversial because their creation requires the destruction of early-stage embryos. Induced cells do not."

 

Interestingly, cloning of embryos to get matched stem cells is rarely getting a mention in reports on stem cell science these days; again, smart money can see no justification in pursuing the never-achieved and expensive goal of cloning yourself into a twin embryo in order to extract (still-imperfectly-matched) ES cells, when any corner lab can get the exact same (and perfectly matched) cells from a speck of your skin.

 

In this report, Robert Lanza is quoted as having 'cloned embryonic stem cells'. He did not. Nobody has got a cloned embryo to that advanced stage yet. Not a single ES cell from all of cloning's millions of dollars and incalculable abuses of human life. By contrast, iPS is "one of those good news stories" both scientifically and socially – and Lanza wryly remarks: "It's great that Al Gore supports iPS reseach, but who doesn't? Even the pope and the Catholic Church are on board." Apparently that odious company is not enough to deter fellow traveller Gore, and AESCR is very glad to have him – and Oprah – and all reasonable people – on board.

 

Article at http://www.usatoday.com/tech/science/ethics/2009-04-14-gore-stem-cells_N.htm

Oprah's moment of truth: "the stem cell debate is dead" thanks to iPS...

Ladies and Gentlemen, you have to take a look at this ‘teachable moment’ on that leading scientific peer-reviewed programme, Oprah. See http://www.oprah.com/media/20090319-tows-dr-oz-brain

What a sight: Michael J Fox there suffering Parkinson’s (he is the number one ill-informed agitator for ESC research) being told by Oprah’s resident medical expert, Dr Oz, that “the stem cell debate is dead” because we can now “take a little bit of your skin” (here he touches Fox’s arm) and take it back to the same as embryo stem cells… Here is what was said, starting at about 2min 04 into the interview:

“I think, Oprah, the stem cell debate is dead, and I’ll tell you why… The problem with embryonic stem cells is that they come from embryos, like all of us were made from embryos, and those cells can become any cell in the body, but it’s very hard to control and they can become cancer”… (this is at 2min35, and MJ Fox looks a little more restless at this point, and Oprah is tight-lipped, sensing a ‘non-PC moment’). “But in this time of fighting that we’ve had – which did I think slow down research – there have been a huge amount of changes. In the last year we’ve made 10 years’ advancement… and here’s what the deal is: I can take a little bit of your skin, take those cells, and get them to go back in time so they’re like they were when you were first made. And then they will start to make that dopamine.

“And I think that those cells – because they won’t be as prone to cancer because they’re your genes – will be the ones that will ultimately be used to cure Parkinson’s. And nobody can tell how fast we can do this, but I’ve talked to a lot of experts in this field, but I think we’re single-digit years away from making a big impact on the lives of Parkinson’s disease, but not only Parkinson’s diseases, also diabetics, heart attack victims, people who had a lot of problems…”

Remarkable that this word of truth – which validates President Bush’s policy of funding the search for ethical alternatives to embryos research - should ever be heard on the Oprah (Obama’s #1fan) show. I can think of one constructive explanation: the departure of Pres Bush means there is no longer a visceral need for the Oprah-liberal camp to promote ESC / cloning just as part of a culture war against Bush; they are free to be more even-handed about stem-cell science. In the same way, there is no longer a need for the international left-liberals to hate America as part of hating Bush; since Obama, they are free to be more even-handed about America. So perhaps under Obama the Bush-haters will be free to acknowledge the shortcomings of ESC / cloning in a way they couldn’t under Bush.

One problem with the Oprah doc’s comments: there seems to be a pervasive notion that iPS cells, as he said, ‘won’t be as prone to cancer’ as ESCs. I do not agree with this. The teratoma downside is exactly the same. I think Dr Oz is muddling the teratoma risk with the cancer risk associated with viral integration used to obtain iPS (and a further minor muddle - Dr Oz should know that this 'viral cancer' concern has now been laid to rest with virus-free techniques for iPS- see earlier Blog).

I always remind people that iPS cells are no more likely than ESC to be used in direct transplant, as the risk is the same – only adult stem cells can be safely placed in the human body without tumour risk. Conversely, iPS cells are as good as ESC for any research (or generation of transplantable terminal cells) scientists might want to do.

Still, apart from the slight muddle at the edges, this Oprah-Fox moment was highly significant as a breakthrough into public consciousness of the true shape of stem cell science – and as a vindication of the thesis of this website: that cloning is dead, and ESC science is peacefully dying.

For Scholars: iPS journal references up to March 2009

Please see reference document at http://docs.google.com/View?docID=dcpmpcfg_8dq3k8vcb&revision=_latest