Stem Cell Research


Adult stem cellsI haven’t been reporting on stem cell research lately, but there has continued to be a flurry of advances in the field.  None of them, however, involve embryonic stem cell research.  All of them involve adult stem cells, cord blood stem cells, or induced pluripotent stem cells (adult cells reprogrammed back to an embryonic state). 

The latest advance was announced earlier this month.  Scientists extracted stem cells from a two year old girl’s bone marrow and created a new windpipe with it in less than a week.  Growing one organ from the cells of another body part is truly astonishing work!  

Here are some other recent medical advances in non-embryonic stem cell research that I have not reported on: 

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Adult stem cell research has been booming.  There are so many advances that it is hard to keep up.  Just recently researchers were able to take adult human skin cells, convert them back to an embryonic state, and then with a string of chemical cocktails convert them into heart cells that were capable of being transplanted into rats.  While not yet ready for human trials, this is a major milestone that may one day give real hope to those who have suffered heart attacks.

 

HT: Wesley J. Smith

Justice Lamberth

Last summer I informed you that Justice Lamberth ruled Obama’s embryonic stem cell policy illegal, arguing that it violated the Dickey-Wicker amendment which prohibits the use of federal funds for destructive embryo research.  Lamberth slapped a preliminary injunction on the policy, suspending all use of federal money for embryonic stem cell research.  Shortly after, an appeals court lifted the injunction while they were considering the appeal against Lamberth’s decision.  On April 29, the U.S. Court of Appeals in Washington finally ruled against Lamberth’s interpretation of the Dickey-Wicker amendment, 2-1.  President Obama’s policy stands.

A faster, safer, more productive method has been discovered for turning adult stem cells into an embryonic-like state (induced pluripotent stem cells).

Catching up on the news….

Last year (March 9, 20010) President Obama signed an Executive Order overturning President Bush’s stem cell policy that allowed federal funding for stem cell research on stem cell lines created prior to August 9, 2001, but not after.  President Obama wished to expand federal funding to include stem cell lines created after August 9, 2001.

Ironically, two days after issuing his EO, President Obama signed into law the annual appropriations bill which included the Dickey-Wicker amendment.  This amendment, which has appeared in every appropriations bill since 1996, specifically prohibits the use of federal funds for research that involves the destruction of human embryos.  The amendment reads:

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In May of this year Gallup polled Americans to determine what behaviors they found morally acceptable and unacceptable.  Sixteen behaviors were evaluated, and here are the results:

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Investors Business Daily has an article on California’s Proposition 71 that passed five years ago, which secured $3,000,000,000 dollars for embryonic stem cell research.  They note how the California Institute for Regenerative Medicine, which was created by the proposition and oversees the distribution of the research money, has shifted its focus to adult stem cell research.  Why?  Because ESCR is not panning out to be the promising research the supporters of prop 71 promised it would be.  While this is good, they note how it appears to be a bait-and-switch: 

To us, this is a classic bait-and-switch, an attempt to snatch success from the jaws of failure and take credit for discoveries and advances achieved by research Prop. 71 supporters once cavalierly dismissed. We have noted how over the years that when funding was needed, the phrase ‘embryonic stem cells’ was used. When actual progress was discussed, the word ‘embryonic’ was dropped because ESCR never got out of the lab.

They conclude by noting that “it is ESCR researchers who have politicized science and stood in the way of real progress. We are pleased to see California researchers beginning to put science in its rightful place.”

HT: Wesley Smith

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CIRM is the CA agency that oversees the distribution of 3 billion dollars for stem cell research in CA.  The agency was created by constitutional amendment via a ballot initiative in the 2004 election.  From its inception, it has directed most of its energies and funds to promoting embryonic stem cell research (ESCR).  It seems, however, that they have finally caught on to the fact that ESCR is not the most promising area of stem cell research.  Of the $230 million in grants awarded to 14 institutions yesterday, 10 of them were for adult stem cell research (ASCR).  Good.

HT: Wesley Smith

In my previous post I discussed President Obama’s recent Executive Order to expand the number of embryonic stem cell lines eligible for federal funding.  It turns out that’s not all the president did.  Part of the Executive Order entailed revoking President Bush’s Executive Order 13435 (issued June 20, 2007), which made it a priority to fund research into alternative methods of obtaining pluripotent stem cells-methods that do not involve the destruction of embryos.  That policy was largely responsible for the iPS breakthrough that revolutionized the field of stem cell research.

Why would Obama revoke that Executive Order?  The most promising areas of stem cell research have been those that do not involve the destruction of embryos (adult stem cells, cord stem cells, iPS).  Why would he pull funding for the most promising areas of stem cell research, and direct those funds into the least promising area of research: ESCR?

This is ironic in light of Obama’s own stated support for “groundbreaking work to convert ordinary human cells into ones that resemble embryonic stem cells.”  It is also baffling given his own admission that to-date, ESCR has not produced therapeutic benefits.  Contrast this to research using alternative sources of stem cells, which have yielded more than 70 treatments.  It doesn’t make any sense to put all of one’s eggs in a basket that is both medically unproductive and ethically suspect, when there are other baskets that are both medically productive and ethical.  It seems Obama is being driven by an ideology that is more concerned with promoting research involving the destruction of human embryos, than he is with funding research that is yielding actual therapeutic benefits for sick Americans.  So much for putting science ahead of ideology.  If he was interested in science, he would put his money on ethical alternatives to ESCR such as iPS.

On Monday March 9, President Obama fulfilled a campaign promise by issuing an Executive Order to expand the federal funding of embryonic stem cell research (ESCR).  While the move was expected, it is baffling given the fact that recent advances in the stem cell research field have made ESCR technologically passé.  Just over a year ago scientists were able to come up with a morally benign method of obtaining the biological equivalent of ESCs, called Induced Pluripotent Stem Cells (iPS).  iPS cells have the advantage over ESCs in that they do not require the destruction of human embryos or cloning to obtain them, the process of creating them is simple and less expensive, they do not face the problem of somatic rejection when used therapeutically, and they promise a limitless supply of pluripotent stem cells (stem cells that can become any of the body’s 220 cells) for scientific research.  Given the recent technological advances in pluripotent stem cell research, deciding to invest additional money in ESCR makes as much sense as deciding to invest money to make better cassette tapes.  Obama’s Executive Order is out-of-date, and unnecessary.

On the positive side, Obama did not try to hype the potential of embryonic stem cells as have many other politicians.  He candidly admitted that “at this moment, the full promise of stem cell research remains unknown, and it should not be overstated.  But scientists believe these tiny cells may have the potential to help us understand, and possibly cure, some of our most devastating diseases and conditions. … [I]f we pursue this research, maybe one day – maybe not in our lifetime, or even in our children’s lifetime – but maybe one day, others like him [Christopher Reeve] might [be cured via embryonic stem cell therapies].”

On the negative side, however, I find Obama’s reasoning to be malformed.  According to Obama,

[I]n recent years, when it comes to stem cell research, rather than furthering discovery, our government has forced what I believe is a false choice between sound science and moral values. In this case, I believe the two are not inconsistent. As a person of faith, I believe we are called to care for each other and work to ease human suffering.

The dichotomy between science and morality is not a false one.  The two can conflict at times.  We can debate whether the two conflict in the case of embryonic stem cell research, but it will not do to just declare by fiat that there is no conflict.

Interestingly enough, Obama goes on to speak of his own religious moral values, and how they have affected his decision to expand the funding of ESCR.  What I would like to know is why it’s ok for Obama to make policy based on his religious values, but it was wrong for Bush to do the same?  This is a double-standard.  The fact of the matter is that in principle, there is nothing wrong with drawing on one’s religiously-informed moral values to make public policy.  Policies are based on moral considerations, and our understanding of what’s right and wrong is most often informed by our religious convictions.  In this case, however, we have two men with conflicting moral values.  Bush valued all human life – including embryonic life – whereas Obama only values post-natal life.  Bush valued all human life equally, and thus believed it would be immoral to kill one life to save another.  Obama doesn’t value all life equally, and thus thinks it a moral imperative to kill one life to save another.  Each man has a different ideology, and thus a different policy.  So enough with the talk about Bush choosing “ideology over science.”  He chose morality over science.  Obama, on the other hand, is choosing science over morality (although I’m sure he doesn’t see it that way).

Election results did not favor the pro-life cause, but they did favor the traditional marriage cause.  Here is a brief survey of the most important issues:

Abortion

California’s Prop 4 sought to require parental notification prior to a minor receiving an abortion.  It was defeated (52% to 48%).

Colorado’s Colorado Definition of Person Initiative of 2008 (aka Amendment 48) sought to define all human beings from the moment of fertilization as “persons.”  It was defeated (73% to 27%).

Obama was elected President of the United States.  If he does what he says he will do given the chance, he will repeal virtually every restriction on abortion (including partial birth abortion), will repeal the ban on using federal tax dollars to fund abortion, will repeal the ban on funding abortions outside the U.S., and will nominate liberal justices to the Supreme Court (ensuring that Roe v Wade will not be overturned for at least another 20-30 years).  This is probably the greatest setback to the pro-life cause since the Supreme Court re-affirmed Roe in 1992 (Planned Parenthood v Casey).  Not only does he stand

Embryonic Stem Cell Research

Michigan passed a constitutional amendment authorizing the use of “leftover” embryos for stem cell research by a margin of 53% to 47%.

Assisted Suicide

The voters in Washington passed Washington Initiative 1000, a bill legalizing assisted suicide.  It passed with a 59% to 41% margin.  Washington is now the second state to pass such a law (Oregon is the other).

Same-Sex Marriage

Voters in California, Arizona and Florida approved constitutional amendments defining marriage only as the union of a man and woman.

California’s Prop 8 passed 52% to 48%
Arizona’s Prop 102 passed 56% to 44%
Florida’s Amendment 2 passed 62% to 38%

California’s win was particularly important, because the state Supreme Court had just forced same-sex marriage on the state by judicial fiat earlier this year.  California is the first state to rescind the right to same-sex marriage once it has been created by a judiciary.

In my former post, I liked to an article by Rob Stein of the Washington Post.  While the article was well-written, and very informative, I was troubled by one line in particular.  Richard Doerflinger, of the U.S. Conference of Catholic Bishops, has been a prominent feature in the stem cell debates.  He is critical of embryonic stem cell research, but supportive of adult stem cell research.  Here is how Stein prefaced Doerflinger’s response to the news of this breakthrough: “Even the harshest critics of embryonic stem cell research hailed the development as a major, welcome development.”  He then goes on to quote Doerflinger. 

It seems to me that Stein’s emphasis is entirely misplaced given the subject at hand.  Embryonic stem cell research was not the topic at hand, so why bring up Doerflinger’s position on that research?  How is it relevant?  

Furthermore, by prefacing Doerflinger’s quote by saying “even the harshest critics…”, it conveys the idea that Doerflinger would normally be opposed to something like this, but even he thinks it’s great.  The fact of the matter is that Doerflinger is a strong proponent of the very kind of research Stein was writing about.  A more proper and fitting preface would have been, “The strongest proponents of adult stem cell research could not have been more pleased with this breakthrough.  As Richard Doerflinger has said….”  

The fact that his comments were prefaced with a negative tone, related to a different topic, makes me think Stein might have a bias against those who oppose embryonic stem cell research–a bias so strong, that he cannot help but to express it, even in an article that celebrates the success of the very kind of research his ideological opponents have championed.  

Or maybe it was his way of trying to tie this breakthrough into the larger debate over embryonic vs. adult stem cells.  I don’t know, but either way, he seemed to poison the well before letting Doerflinger have his say, and it wasn’t fair.  After all, he never prefaced the comments of embryonic stem cell supporters with, “Even those most critical of the ultimate value of adult stem cell research hailed the breakthrough as a welcome development.”  What else are we to conclude? 

I emailed Mr. Stein these questions.  We’ll see if he responds.

In a major breakthrough, Harvard scientists have been able to reprogram adult pancreatic stem cells into beta cells capable of producing insulin, simply by flipping three genetic switches.  That is cool enough in itself, but the real kicker is that they did this in vivo.  

Last year it was shown that an adult stem cell could be reverted back to an embryonic-like state (induced pluripontent stem cells).  But this process is one that takes place in vitro.  Not only do the stem cells need to be removed from the body, but then they need to be reverted to an embryonic state, then coaxed into differentiating into the desired cell type, and finally be placed back in the body for therapeutic purposes.  The Harvard team skipped all but the third step.  They have shown that adult stem cells can be transformed into other types of cells without being removed from the body, and without having to be retovertered into embryonic form.  Not only does this make for a less invasive procedure, but it would also avoid the current problem facing embryonic and embryonic-like stem cells: tumor formation.  

While this is definitely a big breakthrough, only time will tell whether it can be safely used in humans, and how many conditions can be treated with this procedure.  One thing seems certain, however: this is just one more nail in the coffin for embryonic stem cell research.  It is becoming both impractical, and irrelevant.

Sorry, but I have one more post before leaving on vacation!


Michael J. Fox, in an
interview with Maria Menounos on The Today Show, said he will continue to be an advocate for embryonic stem cell research, even though an alternative method for obtaining the functional equivalent of hES cells has been found. I don’t get it. To my knowledge Fox doesn’t have a financial stake in ESCR. His career is not on the line. He is not aspiring for political office. He is an advocate for ESCR because he wants to find a cure for the Parkinson’s he and many others suffer from, and thinks ESCR is the most promising ticket to get there. Of all the public advocates out there, he is surely most interested in the clinical success of ESCR.

That’s why I am baffled that he would not switch ships at the dock. Why continue to support ESCR when an simpler, more efficient method of obtaining the same kinds of cells has come along? The number of hESCs we can obtain will always be limited to the number of frozen IVF embryos donated to research, or the number of eggs donated for cloning (if human cloning ever proves successful). But with iPS cells, we can create a virtually unlimited supply. All we need is a skin cell! Furthermore, labs all over the world can create iPS cells, whereas only a relatively few were equipped to do ESCR and cloning.

Furthermore, surely Fox must be aware of the fact that moral concerns are largely responsible for the slow pace of ESCR. Why not support the research that everyone agrees is morally acceptable? It can only speed up the progress, because it will enjoy the support of everyone, including the federal government. I can’t figure Fox out.

HT: Jivin J

Ramesh Ponnuru points out how Newsweek’s science correspondent, Sharon Begley, has changed her tune. When Bush vetoed legislation that would have expanded federal funding for destructive embryonic stem cell research, Begley wrote how this might be “a cruel blow to millions of patients for whom embryonic stem cells might offer the last chance for health and life.” Never a mention of the practical drawbacks and deficiencies of ESCR.

Now that an ethical and more practical alternative to ESCR has been discovered, Begley is downplaying the significance of pluripotent stem cell research in general:

While the research was once hailed as leading directly to cures—by turning stem cells into neuronal cells that could be implanted in patients with Parkinson’s
disease, say—it now looks like something much more mundane: another laboratory tool to study different diseases, yielding insights that would launch the slow, years-long search for new therapies. … [H]aving the new method for creating stem cells is unlikely to lead to treatments and cures any sooner than having only the old one.

[I]t will be years before scientists understand reprogrammed stem cells—how to get them to mature into different tissues, for instance.

To a public for whom stem cells equal cure, the real blow will be the realization that the simplistic picture—take a patient’s genes, slip them into an egg, let the egg grow and divide into stem cells that are perfect genetic matches for the patient and transplant those cells to treat diabetes, Parkinson’s, Alzheimer’s—is more fiction than fact. … Instead of yielding cures directly, stem cells— reprogrammed and embryonic alike—will take their place alongside other lab systems for studying disease. They will reveal hitherto-unknown causes and pathways of illness, even pointing the way to new drugs. The typical time between such a discovery and a new drug is at least 15 years.

Talk about going from “Yankee Doodle” to “The Death March”!! Why the change in tune? Many commentators have suggested (and I tend to agree) that the change in tune is political. The reason the Left promoted ESCR was because it put a further hedge around abortion rights (you can’t object to killing the unborn when they are your source of cures, but on the other hand, if ESCR is objectionable on moral grounds, then so is abortion by extension), and it allowed the Left to stick it to the President and conservative Christians (portray them as anti-science, lack of compassion). Now that an undeniably superior method for obtaining what they say they wanted all along has come along, and that due largely to the political policies of President Bush, the tune has to change. Now they have to downplay the significance of stem cell research, and admit that cures from pluripotent stem cells are years away. Oh the irony!

HT: Ramesh Ponnuru

From an MSNBC article regarding the new iPS cell breakthrough:

[James] Thomson said he never believed that cloning itself would produce new therapies – and not just because of the moral and ethical qualms about human cloning. ‘Mainly, it’s just hugely inefficient and terribly expensive,’ he said. Rather, Dolly the sheep – and the pluripotency of embryonic stem cells – pointed to potential treatments that could go beyond cloning, and beyond those precious embryonic cells.” According to Thomson, “My feeling is that somatic cell nuclear transfer was an experimental technique, and it could have led to a mechanistic understanding of how reprogramming could occur. But I was skeptical that it could ever enter the clinic because of practical reasons.”

What a revelation this is. I may be wrong, but I don’t recall Thomson saying any such thing previously. Why didn’t he speak up when CA was asking its citizens to fork over $6,000,000,000 dollars to pay for cloning and ESCR, on the promise that cures were right around the corner, and that the research would bring a windfall of profits to CA? It’s real convenient to play mum until after better research comes along.

Ron Reagan Jr. campaigned for embryonic stem cell research during the 2004 Democratic National Convention. Aware of the fact that many opposed ESCR on moral grounds, Reagan quipped, “The theology of the few should not be allowed to forestall the health and well-being of the many.” From then on, the pro-ESCR strategy was to make this an issue of a war between theology and science; those who want cures, and those who don’t. Commenting on the logic of this, Rich Lowry writes: “Democrats loved this narrative: theology versus science, with its echo of the Inquisition repressing Galileo. It drove the charge that the Bush administration was waging ‘a war on science.’ As if placing ethical bounds on science is a denial of the scientific method and the value of research itself. By this logic, speed limits are ‘anti-driving,’ guardrails are ‘anti-highway,’ and meat inspections ‘anti-food.’”[1]

Exactly! Those with moral objections to certain scientific ventures such as cloning or ESCR are not anti-science or anti-cures. They are people who recognize that the ends do not always justify the means, and that science must be guided by morality lest science become a tool of tyranny.

[1]Rich Lowry, “Science Trumps Politics”; available from http://article.nationalreview.com/?q=ZGE4YTEwOTI0YmY0NjRlNTI5Mjc5NDIzMjA3NWY4Y2Q=; Internet; accessed 27 November 2007.

This may be old news for some of you, but I was on vacation all last week and could not post anything about it until now. Two teams of scientists, one American and one Japanese, have independently discovered a way to revert adult cells into pluripotent form (functional equivalent to embryonic stem cells). This discovery will likely solve the moral dilemma posed by embryonic stem cell research. This is BIG news! See EurekAlert 1, EurekAlert 2, EurekAlert 3, EurekAlert 4, National Geographic News, BreitBart.com, BBC News 1, BBC News 2, MSNBC and and PhysOrg for sample media reports.

Scientists claim embryonic stem cells hold the greatest potential for cures because they are pluripotent (meaning they are able to turn into any one of the body’s 220 cells). The ethical problem with embryonic stem cell research (ESCR) is that to obtain ESCs, the embryo has to be killed. For this, and other practical reasons, alternative methods of obtaining embryonic stem cells have been sought.

What the two teams of scientists just discovered was a means of obtaining stem cells that possess all the characteristics of ESCs (such as pluripotency, indefinite self-renewal, etc.), without having to kill embryos to get them. In fact, this new method does not even involve the use of embryos.

To obtain the pluripotent cells scientists inserted a recipe of four genes (Oct3/4, Sox2, c-Myc and Klf4 in the Japanese study, and OCT4, SOX2, NANOG, and LIN28 in the American study) into adult skin cells (fibroblasts). These genes have the effect of reprogramming the skin cell so that it regresses back to its pluripotent state, becoming the functional (and nearly biological) equivalent of an embryonic stem cell. It de-differentiates the differentiated skin cells just as in cloning, but unlike cloning, the “product” is a pluripotent stem cell, not an embryo. This process is being called somatic cell reprogramming, or cell regression. The altered cells are being called “Induced Pluripotent Stem Cells,” or iPS.

Robert Lanza noted the significance of this breakthrough when he said, “It’s the holy grail. It’s like turning lead into gold.”

Not only is this method morally advantageous to ESCR, but it is practically advantageous as well. There are not enough surplus IVF embryos available for ESCR, and there is a lack of eggs for use in cloning new embryos (not to mention the fact that cloning is an additional moral concern, and has proved unfruitful to date). In contrast, somatic cell reprogramming is an easy process that is not dependent on embryos or donor eggs. We can reprogram as many skin stem cells as there are people with skin! Somatic cell reprogramming has the potential to give us an unlimited supply of pluripotent stem cells. Furthermore, unlike stem cells from surplus embryos, iPS cells are genetically identical to their donor, and thus pose no risk of rejection when inserted into their body.

There are still kinks to be worked out, namely, how to remove the copies of the four genes from the stem cell once they have done their job. The crucial next step 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.”[1] And of course, many of the same practical difficulties involved with the use of embryonic stem cells apply to iPS cells as well, such as their tendency to form tumors, and our lack of ability to control their differentiation. So this breakthrough brings us no closer to developing treatments and cures using pluripotent stem cells. The only stem cell treatments to date come from multipotent stem cells, more commonly referred to as adult stem cells.

Somatic cell reprogramming is so promising that even Ian Wilmut, creator of the somatic cell nucler transfer method of cloning, announced that he is abandoning therapeutic cloning in favor of cell regression. He said, “I am anticipating that before too long we will be able to use the Yamanaka approach to achieve the same, without making human embryos. I have no doubt that in the long term, direct reprogramming will be more productive, though we can’t be sure exactly when, next year or five years into the future.”[2]

Now, the only reason to continue the pursuit of cloning embryos is if we want to birth them, or involve ourselves in genetic engineering of humans. Since those pressing for cloning were so adamant to denounce this “form” of cloning, it will be hard to make a case for it now. I’m sure some will continue to do so, however, because they want to genetically engineer humans, and birth clones. Others have financial interests in ESCR and cloning that are not easily disentangled. A lot of money was bet on ESCR and cloning, so a lot of people have a lot to lose. They will not let go of their money and their interests easily. We’ll have to wait and see how it all pans out.

Last year scientists were able to reprogram adult mouse stem cells so that they revert back to their embryonic form (pluripotent, rather than multipotent). Now, scientists have made the process more efficient. So far it has only been attempted in mice. Learning how to do it with adult human stem cells may take several years, but it is a promising area of research. If successful, there will no longer be a need to destroy embryos (indeed, I don’t think there is a need even now given the success of adult stem cells).

I’ve heard a lot of pro-human embryonic stem cell research (ESCR) politicians talking about the need for “ethical stem cell research” lately. But this begs the question, and ignores the ethical portion of the debate. The ethical debate centers on the way embryonic stem cells are obtained: by killing human embryos. If the anti-ESCR group is right, and killing embryos for their stem cells is morally wrong, then there is no ethical way to conduct ESCR, because it kills the embryo every time. From an anti-ESCR perspective, when a pro-ESCR advocate talks about the need for ethical ESCR, it is as morally intelligible as saying we need an ethical way of killing minorities. There is no way it could ever be ethical, because the act itself is morally wrong!

If one doesn’t see killing a human embryo as unethical, I don’t know what other aspect of ESCR could be considered unethical. A pro-ESCR advocate might respond that how scientists procure eggs for the research might be unethical (paying women for their eggs), but this confuses cloning (in which eggs are needed) with ESCR (in which embryos, not eggs are needed). Of course, conflating the two distinct arms of research is a strategical move on the part of cloning advocates, in which they hope to gain support for cloning (which lacks popular support) by trying to play it off as part and parcel of embryonic stem cell research (which has popular support). But I digress. The fact of the matter is that apart from killing the embryo, there are no substantive ethical concerns with ESCR (excluding those concerns that accompany all medical research).

Of course, as I reported a few days ago, scientists are starting to discover possible ways to obtain embryonic-like stem cells without having to create, or destroy an embryo. That would be the only ethical way to conduct ESCR. Unfortunately, that’s not what the politicians have in mind when they talk about ethical stem cell research, and that’s not the type of research they are trying to pass legislation for.

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