Lung stem cell? Promising, but no reason to take up smoking again...

Very interesting article today in the New Engalnd Journal of Medicine identifying another native adult stem cell, this time resident in the lung:

Human lungs contain identifiable stem cells. In animal models, these cells participate in tissue homeostasis and regeneration. They have the undemonstrated potential to promote tissue restoration in patients with lung disease.

For those without a subscription to NEJM, see the write-up in Forbes.

Very promising as a potential pathway for regeneration of damaged lung tissue.

NHMRC CLONING REVIEW DUE TO REPORT TO PARLIAMENT 27th MAY 2011

Thanks to all who made a submission to the Cloning Review (see Blog entry for Feb 15th).

The large majority of submissions argued against cloning, in light of the new, ethical alternative.

Read all the submissions at: https://legislationreview.nhmrc.gov.au/public_submissions

You can listen to our National Director's comments HERE in an online interview.

The concluding remarks in the submission by Australians for Ethical Stem Cell Research:

I trust that we have made the case that the scientific landscape of stem cell science has changed so dramatically since November 2007 that the argument about the ‘unique necessity’ for cloning no longer applies; that if our Senators and MPs had known in 2006 what we know now, cloning would never have been permitted. Arguments for SCNT/cloning are now marginal: its proposed role in mitochondrial disease is demonstrated here as a conceptual error, and the call to create cloned ESCs as a ‘comparison’ to iPSCs, even though we know ESCs are functionally identical to iPSCs, is truly clutching at straws. A sense of proportion – measuring the substantial ethical barrier to the creation of human embryos as mere research material, versus the shrivelled residual arguments for SCNT/cloning – should result in recommendations to repeal this inhuman and unjustified practice. 

Our submission online at the Cloning Review

The Cloning Review Committee is posting yesterday's last-day-rush of submissions, including ours, to the legislative review site. There are many well worth a read, over a good red one night this week...

Ours is at the link: https://legislationreview.nhmrc.gov.au/submission/submission-165 and opens with a line of argument tediously familiar to anyone who has followed this blog since 2009, and its predecessor, the pre-Yamanaka, "Conscience versus Con Science" since 2006:

Summary statement

SCNT/cloning is a human corruption and a scientific failure. It is unethical, in that it involves the creation of living human embryos solely for research and destruction. It is unnecessary, in that the stem cell revolution of 2007 has removed the sole scientific argument for cloning: SCNT/cloning is no longer the “unique method” for obtaining patient-matched pluripotent stem cells, in fact it has never obtained even a single human stem cell for all the millions spent and all the embryos created and destroyed. The new “induced pluripotent stem cell” (iPSC) technique has succeeded magnificently in achieving patient-matched pluripotent stem cells where cloning has failed. Further, the iPSC method is ethically uncontentious: it does not use women’s eggs and does not create and destroy human embryos. This Review Committee should recommend repeal of the unethical practice of SCNT/cloning - a practice which since 2007 has no plausible justification - and recommend restoring the long-standing prohibition on the creation of human embryos solely for research.

Action! March 15 Deadline to say NO to human cloning...

We only have until March 15th to tell the federal Cloning Review that we want this inhuman and unjustifiable science banned once again. Please see https://legislationreview.nhmrc.gov.au/2010-legislation-review for ‘how to make a submission’.


Background:In 2006, by just one vote in the Senate, a law was passed allowing human cloning – the creation of living human embryos solely for the purpose of research and destruction. The law bans the cloned embryo from being implanted in a woman’s womb, and decrees that the embryo must be destroyed before 14 days of age, but still permits the creation of embryonic human life solely for exploitation in stem cell experiments and IVF research.

That was wrong and unnecessary then, and even more unnecessary now – since the magnificent breakthrough by Yamanaka in November 2007 of ‘direct reprogramming’ of adult skin cells into the exact equivalent of embryonic stem cells, without ever creating or destroying a human embryo. This revolution in stem cell science means that scientists now have an entirely ethical method to obtain the specialized stem cells that cloning hoped to obtain but never has obtained. Cloning is a failed science; the new Yamanaka method has proven both simple and effective.

Reading:To get the latest on why cloning is both wrong and redundant, read my review article from Viewpoint magazine, “An Obituary for Human Cloning”. And browse this blog for some highlights of the new world of entirely ethical stem cell science - where there is no need for cloning.

Action:
Then please write a submission, however short and simple, to the committee. All we need to convey is that:

· It is wrong to create human embryos solely for research and destruction.
· We understand that cloning (SCNT) is one method of creating a living human embryo, as was confirmed at the Senate hearings in 2006 – the same method used for creating Dolly the sheep.
· We know that, since the Yamanaka 'iPS cell' breakthrough in November 2007 (see my review article) we have an entirely ethical, and proven, method of obtaining the specialised stem cells that cloning hoped (but failed) to obtain, so there is no longer any serious justification for cloning.
· If our Senators had known in 2006 what we know since the Yamanaka breakthrough, cloning would never have been considered, and no laws would have been passed.
· We now want the Review Committee to acknowledge the dramatically changed scientific landscape, and recommend to Parliament that the provisions allowing cloning are no longer scientifically justified, and should be repealed.

As always, the committee is dominated by well-known supporters of cloning (see my December entry on 'Cloning review at last'). That is a disgraceful derailment of a supposedly 'independent' review. However, that is not our primary concern. We need to send lots of careful, thoughtful submissions - even a short summary statement is fine, and there is no need to provide responses in all sections of the review - so they know that the public is aware that the old arguments for cloning no longer apply, that it is now a redundant science supported by unjustifiable laws.

FURTHER COMMENTS by our WA Rep: In 2002 the Commonwealth passed laws permitting research on so called “left over” human embryos but banning the deliberate creation of human embryos for research by any means, including a comprehensive ban on the cloning of human embryos.

A 2005 review of that legislation proposed revoking the ban on cloning and allowing human embryos to be created for research by cloning or by the use of eggs derived from aborted baby girls. Legislation implementing the changes passed the Senate by just one vote. It was given Royal Assent on 12th December 2006.

All states except Western Australia subsequently passed mirror legislation allowing cloning. In WA note was taken of the revolutionary developments in science in November 2007 which allowed pluripotent stem cells to be derived from any body cell by a process which avoided any creation or destruction of a human embryo.

Only Sydney IVF has been issued with licenses to experiment on cloning. Since obtaining the licenses on 16 September 2008 Sydney IVF has used 389 “clinically unsuitable” human eggs (ova) in an attempt to create cloned human embryos. In only 32 attempts was there development to the two cell stage and in no case was the eight cell stage passed. This is well short of the point at which embryonic stem cells could be extracted. The official report on the experiments states: No reproducible method for SCNT [somatic cell nuclear transfer] using clinically unsuitable eggs for the efficient epigenetic reprogramming of human embryonic stem cells to the blastocyst stage has been established to date.

It seems futile to be trying to clone using eggs that are no good at being fertilised. This approach was tried and abandoned by British researchers at Newcastle some years ago. They switched to using fresh, good quality eggs obtained through an egg sharing arrangement with women undergoing IVF at half price rates – a form of payment for eggs.

This approach is currently banned in Australia.

In July 2009 review committee member Loane Skene called for Australia to follow the lead of New York State which broke ranks in the US by allowing payments to women for eggs for research. It seems likely Skene will seek to persuade the committee to recommend this change.
Inducing ovulation in women in order to harvest their eggs exposes them to a massive 239% increased risk of uterine cancer, 150% increased risk of non-Hodgkin’s lymphoma and a 42% increased risk of breast cancer.

Up to 10 percent of patients undergoing induced ovulation experience severe ovarian hyperstimulation syndrome (OHSS) with symptoms including loss of future fertility, kidney or multiple organ failure, and death. Deaths from OHSS include 32 year old Irish woman Jacqueline Rushton, who died in Dublin on 14 January 2003. She suffered a gradual deterioration of her organs, virtually all of which were slowly destroyed. Temilola Akinbolagbe, a young woman who died in April 2005 in London, suffered a more sudden death from a massive heart attack linked directly to OHSS.

You are encouraged to make a brief submission to the legislative review:
- opposing any proposal to allow payment for human eggs for cloning research;
- calling on cloning to be banned because it is a failed approach to obtaining stem cells for therapy and it involves the unethical creation and destruction of human embryos.

Submissions can be made online at: https://legislationreview.nhmrc.gov.au/node/add/submission

Hard copy submissions may be mailed to: Legislation Review, National Health and Medical Research Council, GPO Box 1421 Canberra ACT 2601

Nice in Mice: skin straight to heart cells (forget embryos)

I can’t improve on my comrade David Prentice’s coverage of this latest bit of Direct Reprogramming Wizardry. I wonder if this new way of obtaining perfectly-matched stem cells (with no need for embryos or cloning, and apparently minimising the risks inherent even in iPS cells) will generate the sort of science-media interest that the futile tinkering at Geron generated...

Changing Skin Directly to Beating Heart Cells
by David PrenticeJanuary 30, 2011 http://www.frcblog.com/2011/01/changing-skin-directly-to-beating-heart-cells/

Scientists with the Scripps Research Institute have directly converted adult mouse skin cells into beating heart cells, without using any stem cell intermediate, and without the laborious process of generating embryonic-like stem cells. Using a reprogramming process similar to that for induced pluripotent stem (iPS) cells, they were able to directly produce “spontaneously contracting patches” of heart cells in the lab. The research is published online in Nature Cell Biology.

The group used the same four genes (“Yamanaka factors”) often used to make iPS cells, but switched off the gene activity after a few days, before the cells had a chance to become iPS cells. Then they stimulated the cells with factors to direct them into becoming cardiac-type cells.

According to Dr. Sheng Ding, senior author of the study:
“In 11 days, we went from skin cells to beating heart cells in a dish. It was phenomenal to see.“This work represents a new paradigm in stem cell reprogramming. We hope it helps overcome major safety and other technical hurdles currently associated with some types of stem cell therapies.”

The worrisome type of stem cells is pluripotent stem cells, i.e., embryonic stem cells, which have a propensity to grow out of control and form tumors.

Back in 2009, similar story titles (converting skin to beating heart cells) appeared when a group used skin cells to make human iPS cells (pluripotent, embryonic-like stem cells), then turned those iPS cells into cardiomyoctyes in culture. But because of the embryonic-like nature of iPS cells, their practical application for patient transplant is in doubt. When pluripotent cells are injected in mice, they cause cancer-like growths.

Direct reprogramming, going from one cell type to another without forming a pluripotent stem cell, offers a way around the practical problems of pluripotent stem cells. Several other groups have shown the possibility of direct reprogramming to form various tissue types.

Meanwhile, adult stem cells have already successfully treated patients with chronic heart failure.

Cloning Review at last! If you didn't laugh, you'd cry

This is part disgrace, part farce. A Review that is only announced a few days after the final date at which the statutory report was meant to be completed and tabled (i.e. within four years of the date of Royal Assent which was 12th December 2006); a Government Minister who does not appear to know the effect or subsequent history of the legislation to be reviewed; a new Committee of Review featuring the architect and chief activist of the last Review! What a display of government amateurishness, and what a shamefully cynical process for conducting a new Review on such a contentious matter.

Here is the release from the Federal Minister for Mental Health and Ageing, Mark Butler, and the poor bloke can't get much right. Take this, for instance:

The Acts, passed by the Australian Parliament in 2002 and followed by complementary state and territory legislation, banned human cloning...

No, Minister. For the record, the Acts from 2006 were not followed by complementary state legislation, at least in Western Australia, because that enlightened State (early 2008) rejected the federal laws in the light of the recent Yamanaka breakthrough in 'direct reprogramming' (in Nov 2007) that rendered cloning redundant. And let's cut the weasel words that the Acts "banned human cloning". The whole point is that they allowed human cloning - go ahead and create as many embryonic humans as you like, just do not let the cloned human embryo be brought to birth. Hence the title "Prohibition of Human Reproductive Cloning", i.e. live-birth cloning. There is no prohibition on cloning, provided the embryo is destroyed in research prior to 14 days of age. Create, but be sure to kill, or you will have broken the law under this Act. Nice, that.

As to the makeup of this committee: shame, shame, shame... As mentioned, Prof Loane Skene, Chair of the last Review (the Lockhart Committee) and a leading lobbyist for cloning, gets a guernsey again: how sweet to get to review her own handiwork, since the 2006 legislation is almost verbatim the recommendations of her Committee. And not only that - she has gone into print as recently as October this year, in the peer-reviewed journal of public affairs, Viewpoint, stating that the current cloning laws are not needing any changes. How prejudiced can a review Committee member possibly be!

Well, a close second for publicly-stated prejudice is the sole scientist on the Review Committee, Prof Ian Frazer. He has been an outspoken activist in favour of cloning, and used the full authority of his role as "Australian of the Year" in 2006 to lobby MPs and Senators. He wrote an influential and, in my view, gravely misleading letter on that letterhead to MPs and Senators on the eve of the vote in 2006 on the current legislation. His letter systematically rebutted the case our association had put to the Parliament (including a full page national newspaper ad only days earlier) as to the superiority of adult stem cells and the hype over embryonic stem cells and cloning.

Most outrageous was his claim in the letter that the problem of tumour formation (which in truth is the fatal flaw in embryonic stem cell / cloning science and not a clinical problem at all with adult stem cells) is really a problem with all stem cells! "Any potential for cancer formation would be inherent to stem cells from any source (adult or embryo)", he writes. So there! A pox on both their houses, says this authoritative scientist! Load of nonsense - the truth is that tumours in embryonic stem cell experiments are an accepted and expected problem, while adult stem cell experiments are notably free of tumours. Even the International Society for Stem Cell Research acknowledges (paragraph 2) that "embyonic stem cells themselves cannot directly be used for therapies as they would likely cause tumors" - but that problem does not apply to adult stem cells. Either Frazer does not understand this central, highly practical problem in embryonic stem cell science, or this was a deliberately misleading message sent to MPs and Senators on the eve of the vote - effectively countering our truthful argument that only adult stem cells could be safely used in direct treatment, as only adult stem cells were safe from the risk of tumours. And now he is on the Review Committee!

In our national newspaper ad we had stated, correctly: "Embryonic stem cells remain unproven in animals and unusable in humans - for reasons such as tumour formation - while our own adult stem cells are safely used in many human conditions." By way of rebuttal Prof Frazer claimed, astonishingly, that "there are no therapeutic uses of stem cells (whether embryonic, adult, or generated by nuclear transfer)". His claim set the B-S metre swinging wildly, given that by late 2006 we had hundreds of patients showing therapeutic benefits from adult stem cells - admittedly early and often small-scale, but certainly 'therapeutic uses' - in a wide range of conditions, including heart disease, wound repair, corneal repair, auto-immune disease. And of course exactly zero with embryonic stem cells. Again, a more truthful statement confirming that there are, and were, adult stem cell therapies, is found at the ISSCR site (paragraph 3) - referring to conditions and trials that were published before Frazer wrote his letter to Senators:

The range of diseases where stem cell treatments have been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used is blood stem cell transplantation to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community.

But 'these therapies' were flatly denied by Frazer in his letter to Senators on the eve of the vote. Frazer's was a muddled as well as misleading claim about 'no therapeutic uses', given that later in his letter he acknowledged therapeutic uses for adult stem cells in bone-marrow transplants, but it was certainly effective in persuading our representatives that our side of the debate was wrong and they had better allow "all avenues of research" to proceed. On any honest comparison of the actual science versus what he gave our MPs to believe,  how is that intervention not an abuse of his authority as "Australian of the Year", in my view misleading our elected representatives on the very eve of the vote? And how then is such a politicised scientist considered suitable as the sole scientific member of this 'independent' Review Committee?

He concluded his "Australian of the Year" letter to MPs and Senators with as shameless a piece of emotional arm-twisting as I have seen, playing the 'sick child' card:

The decision you make... has the potential to impact on the quality of medical treatment our children receive. Will our children look back in 25 years and say "Our parliamentarians made the right decision, that gave us access to cures for diabetes, heart disease, and neurological disorders", or will they be forced to travel to the US, Europe and Asia to seek treaments?

I have no problem with a known cloning advocate like Frazer being on the committee, as long as his influence could be balanced on the committee by a scientist of equal standing, somebody who could challenge his dubious factual claims - but there is nobody. From Queensland we have an expert in the ethics of midwifery! What earthly use is she on a cloning review committee - unless she wants to upgrade the legislation to allow live-birth cloning so she can expound on the ethics thereof? In Queensland we have giants in the field of stem cell science, like Prof Alan Mackay-Sim or Prof Peter Silburn, so why not put them up there with Frazer? Aha! But they are likely to bring some rigour to bear on the actual facts of stem-cell science, especially post-Yamanaka, and at times have exhibited the personality disorder of 'cloning scepticism', and that would never do! In Victoria we have one of the most senior research scientists in the country, and an expert on stem cells where Frazer certainly is not - Prof TJ Martin - who would have been the obvious choice for this Review, if sound science was the true objective. But no, Victoria gives us the lawyer and serial committee activist, Skene.

This committee is, like its predecessor, another cynical exercise in getting the Report that the "just research everything and who gives a damn about human embryos" lobby desires. Good luck to the token Catholic ethicist on the Committee, but because he has no other scientist on the committee to challenge the well-established views and advocacy of Prof Frazer and Prof Skene, I suspect his voice will be drowned by the noise of the committee's big guns.

Or will Frazer and Skene astonish their critics and prove to be objective and balanced about the diminished place of cloning in the new era of stem cell science? Will they acknowledge that the one great argument for cloning in 2006 - that SCNT was the only way to obtain specialised pluripotent stem cells that exactly match the patient - is no longer a valid argument (post-Yamanaka, in the new era of iPS direct reprogramming)? Will they accept that, had we known in 2006 what we know now, no legislation on cloning would ever have been drafted, let alone passed on the floor of Parliament?

Therefore, will they have the grace to conclude that this divisive practice of cloning, which in the view of many desecrates human life and violates the profound meaning of human reproduction and relationships, is no longer justified and can now safely be repealed in favour of the non-contentious iPS alternative? Please, please, let it be so.

Giving the tale of two-dad-mice a miss

Just a bit of idle mutilation by scientists who were once little boys pulling wings off butterflies. This creepy step is not coming anytime soon (or distant) to a gay couple near you, for the same pesky reasons of human complexity that have foiled the cloners of men rather than mice.

Try the Wall St Journal for an outline of this "weird" experiment (to use the word of the principal mutilator); or get as much explanation as you would ever need from Dr David Prentice at his FRC blog.

Ah yes - the other 'ESC' treatment!!

After Geron Corp and the non-ESC non-treatment trial in spine inury, I see that Advanced Cell Technology (ACT) has made its own bid for five minutes of fame, this time with a rare form of macular degeneration (Stargardt's macular dystrophy). Five minutes is all it takes for intelligent people to ask the same questions I posed re Geron:


1. Given that we can do all this with adult stem cells (for example, see HERE) why mess with embryos (with their inherent problems of tumours, and immune supression, let alone the ethical ugliness)?


2. Even if you really really really want to use tumorigenic pluripotent stem cells, why not spare the patient the need for immune suppressant drugs and use iPS cells (for example, see HERE) as a source of the transplatable cells - because they at least match the patient?

What mug would turn away from the obvious advantages using safe, genetically perfect ASCs and instead use dangerous pluripotent cells? And if only the latter "will do", what mug would use 'foreign' ESCells when he could use genetically matched iPS cells? For as the old song goes: "Anything 'e' can do, 'i' can do better" especially when it comes to matching the patient's immune system.

Still, if all your company's resources and IP is tied up with embryos, and the FDA is fool enough to grant your reckless and unjustified experiment on human subjects, and your legal liability is sufficient - then it is understandable (although still unjustifiable) that you would proceed with ESC-derived cells.

Hype-alert: as with Geron so with ACT, not a single ESC will ever be injected into a patient (despite the breathless headlines in the media) because, of course, you can never do that. Likewise, this ACT trial is not a treatment: is is just a phase 1 safety trial to see what harm the ESC-derived cells might do to the subjects. So while it is understandable for the CEO to talk up the company's trial, it is not as he puts it "a game changer for the medical community". The only game changer will be when steady minds and smart investment finally expose this embryo-tinkering for the redundant stunt that it is. Then we can divert our energies to the two fertile fields of stem cell research: ASC for safe direct therapies and iPS for ethically uncontentious genetic research and drug development.

My review article on the Death of Cloning

For a glossy summary of why cloning is a blighted science, and why our Parliaments can and must remove the legislation that underpins cloning, here is a link to my peer-reviewed article in the latest edition of 'Viewpoint'. This is a public-issues journal put out by the Australian Christian Lobby, and features a pair of opposing opinions - in this case the other side was put by Professor Loane Skene, former Chair of the Lockhart Review Committee which recommended cloning to the Federal Government back in 2005.

To read her article, and all the other valuable material in the October edition of Viewpoint, please buy one, or a dozen and give them to friends for Christmas, via http://www.viewpointmagazine.com.au

As for my article, feel free to circulate - but mention Viewpoint as the source, thanks.

Turn skin cells to buckets of blood cells – and forget embryos

Something funny happened on the way to reprogramming a patient’s skin cell to an iPS cell. An astute observer at McMaster’s University, Canada, noticed that some of the cells did not fully reprogram, and the half-baked cell had that donut-look of a red blood cell. Now they have learned to control this partial reprogramming, and the McMaster’s news release yesterday tells the story:

Making blood from skin does not require the middle step of changing a skin stem cell into a pluripotent stem
Hamilton, ON (November 7, 2010) – In an important breakthrough, scientists at McMaster University have discovered how to make human blood from adult human skin.
The discovery, published in the prestigious science journal Nature today, could mean that in the foreseeable future people needing blood for surgery, cancer treatment or treatment of other blood conditions like anemia will be able to have blood created from a patch of their own skin to provide transfusions. Clinical trials could begin as soon as 2012.

Mick Bhatia, scientific director of McMaster’s Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine, and his team of researchers have also shown that the conversion is direct. Making blood from skin does not require the middle step of changing a skin stem cell into a pluripotent stem cell that could make many other types of human cells, then turning it into a blood stem cell.

Samuel Weiss, professor and director, Hotchkiss Brain Institute, University of Calgary, said: “This groundbreaking work from Mick Bhatia’s lab is both fascinating and important. It heralds a new age by discovering a role for ‘directed differentiation’ in the treatment of cancers and other disorders of the blood and immune system.”

Yet the ABC cannot help itself. Reporting on such a compelling breakthrough using our own adult cells, it still has to perform a wanton genuflection to those embryonic wannabes. Having established that the Canadian technique does indeed produce human blood cells that exactly match the patient – the authentic pot of gold at the end of the stem cell rainbow - and does it without messing with eggs, embryos or cloning, ABC reporter Jennifer Macey still has to get the token wet-blanket scientist to say that “unlike embryonic stem cells, which can produce millions of new cells, it's still unclear whether the adult skin cells will be able to produce enough blood.”

Yeah, right – show us a single embryonic stem cell that can produce even a single red blood cell that matches even a single human patient. There is none. Zero, zip. To achieve such a cell you first have to successfully clone the patient into her twin embryo, extract the embryonic stem cells, and then differentiate those ESCs into a blood cell. What utter folly. What an insult to our intelligence, pretending such a futile embryonic pursuit deserves equal billing with direct reprogramming of adult cells. It is time for pro-cloning scientists to get over their wounded pride in backing a dud science, stop wasting our hard-earned tax dollars, and stop pretending to ABC journalists and others that cloning is anything but an expensive and offensive failure.

Meantime, let the magnificent work on the near-alchemy of ‘directed differentiation’ proceed apace.