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Stem cell construction

In a world where space is equated with prestige, California stem-cell researchers are going to be getting a lot more of it. The California Institute of Regenerative Medicine has just awarded $270 million dollars for buildings to institutions all over the state. These funds will be matched by even more than that amount by other donors.

Here is some coverage of this boon to scientific buildings.
The San Diego Tribune consistently does a nice job; this article focuses on the $43 million coming in locally. Another is more general.
The San Francisco Chronicle splashed it over much of its front page and seemed to me to do the best job of covering the impact on California.
The New York Times gave it a mere 600 words, and I couldn’t find it in the LA Times.
And of course, Nature had a full article on CIRM and the national impact on stem-cell science last week. ( See my ramblings and links )

I’d pulled clips on government investment in infrastructure several weeks ago (I thought I’d have time to write in-depth on this but haven’t), and I was surprised to discover that government really doesn’t traditionally invest that much in infrastructure. CIRM is limited to spending 10% of its funds for construction.

I found a lot of skepticism on academic construction in general but haven’t done much reporting. CIRM quotes Paul Berg saying that the hardest problem for people getting into stem cell research is the lack of facilities. Back in February, the head of the Buck told me that if they got the funds to construct a new building for stem cell research, they’d have little trouble filling it with scientists. ( The Buck got $20.5 million to fund the $41 million building.)

Here’s an article from the Economist on whether better facilities for universities are a good idea. (It does not address stem cells particularly, and you’ll need a subscription.) Journalist Dan Greenburg has also written on the unprecedented era of laboratory construction going on. Here’s a recent, statistics filled pdf on college construction.

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CIRM and the shape of stem-cell science

Nature has just posted a thoroughly reported feature on how the California Institute of Regenerative Medicine and its billions of dollars will change the shape of stem-cell science and infrastructure. (For a more personal view from a Texas scientist, see our commentary by Peggy Goodell .)

One point the feature makes is that CIRM’s board members also serve the institutions that receive funding from the institute. There are, of course, a welter of rules aimed at avoiding conflicts of interest, but CIRM has still found itself subject to strong criticism. One retired journalist has even started a blog devoted to the institute’s scrutiny. An editorial accompanying the Nature feature calls for strong governance.

Still, CIRM is not the only stem-cell agency facing such charges. A report this week from Integrity in Science reports that “at least 11 of the 25 voting-members of Health and Human Services’ Advisory Council of Blood Stem Cell Transplantation have financial ties to cord blood-banking and transplantation industry despite a committee charter stating that such conflicts should be limited.”

What does seem unique to CIRM are the multiple sources of “two-masters” tension: it must support basic science and clinical applications ( see my interview with Marie Csete) ; it must succor biotech companies but make sure that patients and other scientists can access their technology (see my article on CIRM grants to businesses ). Even its organizational structure is split. (See my article on CIRM’s search for a president .)

I’ve asked CIRM officials about this before. I’m told that such strains are indeed difficult to balance, but done right they are a source of strength. I’ve asked non-CIRM experts about it too. They tell me it’s easy to make bad investments in hot new fields, but good ideas often wither early because they can’t prove their worth. And I've asked everyone whether CIRM’s funds are a good use of money, and they say what journalists hate to hear: time will tell.

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Of in vitro meat and cloned drug-sniffers

The entrepreneurial spirit may boost efforts to turn stem cells into fried chicken. It has already expanded the ability to clone dogs. If ideas like these could be tweaked just a bit, they could help spawn research tools the biomedical community really needs.

An idea that might boost cutting edge research (and save animal lives) is coming from a surprising source, People for the Ethical Treatment of Animals. Saying that stem cell science could make in vitro meat possible, PETA has just put up a $1 million prize for the first candidate to make a palatable in vitro chicken product and sell at least 2,000 pounds of it over 10 states.

If PETA had picked pork instead, the research might have had some benefit for the biomedical research community (though it may also have facilitated more experiments using pigs.) No one has worked out a way to get robust pluripotent stem cells in sufficient quantities from species besides mice, monkeys, and men.
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Stem-cell skin creams, a San Diego collaboratory, and legal blogs

An article in Tuesday’s LA Times patiently explains that expensive bottles of skin cream sold in doctors’ offices and online do not actually contain stem cells. They don’t have much science either. Other companies are marketing services to store stem cells in menstrual blood. The uterine lining is highly regenerative, but the science is early.

In San Diego, four independent institutions are planning to build a common $115-million facility for stem cell science. Teri Somers covers it well, and some commentators are passionately against. The California Stem Cell Report has comments on this, plus a lively discussion on the meaning of “trivial” in terms of the contribution the California Institute of Regenerative Medicine claimed to have made and actually made to research leading to clinical trials. (The posts are on April 17 and April 15) Back in August, Nature Reports Stem Cells conducted a survey on how recipients of innovation grants intended to use them, noting that the Institute had been kept from disbursing most of the funds it had been awarded)

Keep reading for most posts that caught my eye

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Meetings this week to help embryonic stem cells’ head for the clinic

This Thursday and Friday, the FDA deliberates on how to decide that cells derived from embryonic stem cells are ready to be tested in humans. On Saturday and Sunday, patient advocates and stem-cell researchers meet in San Francisco to talk about how to accelerate discoveries and therapies.

Both indicate a growing momentum for moving stem cells into applications. I wrote a preview article on the FDA discussions. The FDA’s got a difficult job to do. It has to make sure that it doesn’t slow down therapies for horrible, debilitating diseases and that human subjects aren’t exposed to dangerous procedures. This meeting is regarded as a first step for moving embryonic stem cells into well-regulated clinical testing.

I’ve never attended an FDA Advisory Committee meeting before, and I called several people to get a sense of what to expect. One of them was Michele Keane-Moore, a former cell-product reviewer with FDA who is now with the Biologics Consulting Group. She told me that the public forum marks a good learning opportunity for the agency. FDA officials have discussion with many companies, she says, “but all of that work is confidential and can’t be discussed.” Now, she says, “A lot of the questions will be aired in a public forum, so all the stakeholders can say what their concerns are.” the transcripts will eventually be made available for this meeting. Keane-Moore believes the discussion will be similar to the one held in July 13 on stem cells in neurological diseases. You can get to it here.

You can read more in the Nature article, but the FDA is mainly worried that the animal tests used to assess safety problems aren’t good enough and that they won’t know until too late that the transplanted cells are causing harm rather than benefit. The FDA has to make these calls all the time, but there are a couple reasons why these cells are cause for concern. One is that the animal safety tests often require animals to be bred to lack immune responses or to be on immunosuppressive drugs (mouse bodies would attack human cells otherwise), so they want to figure out the limitations of these tests.

Also, stem cells are very different from drugs because cells can multiply and change. That makes them harder to predict. If you put the cells in an environment where they can grow quickly, a low dose of cells could become a high dose. That can’t happen with drugs. Of course, everyone also hopes that these cells can bring about cures for diseases that so far seem intractable to regular drugs.

If you have something you want me to have my eyes out for at either of these meetings, please send me an email or add a comment below.

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Recent editorial is meant to urge caution, not attack a scientist

I’ve gotten a couple of emails about an editorial Nature recently ran urging scientists in the iPS field not to rush. It starts by relating an anonymous attack against Shinya Yamanaka for a minor problem. That’s supposed to get folks’ attention, but it is absolutely not the point of the article, which is to urge caution to everyone who is in and rushing into a very hot, very young field that is also politically charged.

The article is not questioning Shinya Yamanaka as a scientist. (It’s common for mistakes to slip through, and there are mechanisms to correct that.) The editorial is about what happens (confusion) and can sometimes happen (fraud) in hot, new fields, and this is going to be even worse for stem cell scientists because the field is politically charged as well. Shinya Yamanaka has already dealt with the accusations in a way that seems to have satisfied Science, and so delving any more into them would actually elevate the accusations of an anonymous emailer, giving the accusations more attention than they deserve.

The idea for the editorial started after PrimeGen decided to publish its findings on viral-free reprogramming by press release. Here was an accomplishment that the whole community was waiting for, but no one could assess it, and so Nature felt that we needed to say something about how people need to be more patient in a hot field. And then a few days later, the anonymous email got sent to many journalists and journal editors, and it seemed a call for caution was even more necessary.

So again, the editorial is urging caution in a hot, politically charged field. It is not about one of the field’s best-loved and most-respected scientists.

I’ll blog again as I get more feedback and hear more thoughts, but I wanted to get this up quickly. In the meantime, I want to say that much thought went into this editorial. You might be interested in how I think some decisions are made. (I don’t have first-hand knowledge of much of this, but I think I can guess.) Also, I should emphasize that stuff I've written above is just me; I haven't yet weighed in on the collective wisdom of NPG.

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Patients paying for stem cells are probably getting bad science

Desperate patients need help separating legitimate researchers from quacks, said representatives the biggest organization for stem cell researchers, who announced that they’d decided to draft guidelines for how basic research on stem cells can be responsibly “translated” to research on human patients. The guidelines will cover embryonic stem cells plus those collected from cord blood and adults, as well as stem cells induced from differentiated cells.

At a press conference in Half Moon Bay, California, a panel of highly influential officials and researchers in stem cell science said they were alarmed at “medical tourism” in pursuit of questionable and potentially harmful stem cell procedures. The only established stem-cell treatments are for a handful of blood diseases, they said, but advertisers promise cures for every imaginable disease. Story Landis, head of the National Institute of Neurological Disorders and Stroke and George Daley, president of the International Society for Stem cell Research said their organizations were besieged by patient queries about treatments whose risks and benefits are unknown. The ISSCR plans to produce guidelines to help such patients and their families assess whether practitioners’ claims are credible.

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Stem-cell researchers and stem-cell research advocates

Tuesday night and the night before, I went to events designed for scientists and non-scientists to mingle. It made me think about what stem-cell-research activists tell me frustrates them most about stem-cell scientists.

On Monday night, a complete stranger made dinner for me and others he’d identified in the stem-cell field. Peter Kuperman, a hedge fund manager who likes to cook, hosts modern-day salons on topics he finds interesting. And though I had misgivings (surely only psychopaths and pushy salespeople invite strangers into their homes), I went and found that it was exactly what he’d billed it to be.

It was nice to see scientists in their human contexts: sleepy from peer-reviewing a manuscript, worried about finding the best school for their children, excited for their spouses’ careers. It was instructive to see how what has become conventional wisdom to those inside the field is still news to those outside it.

On Tuesday night, I went to San Francisco’s Ask-A-Scientist: free monthly lectures by scientists to standing-room only crowds. As part of a discussion on ancient science, our speaker defined its modern counterpart: a consensus-driven community that cautiously advances hypotheses backed by evidence collected through rigorous methodologies.

I hadn’t considered the consensus-driven aspect, but it’s true. One current scientific controversy is whether certain tumours arise from stem-cell-like progenitors or from differentiated cells. Those in one camp don’t seek to split from those in the other camp; they want to convert them. They want that conversion to be honest, not forced; those in one camp should be drawn to the other not by bullies or charismatic personalities, but through logic and data. That’s why many reviewers want to be anonymous, and why some scientists want authors to be anonymous as well.

Consensus building through logical arguments built on empirical data is much of what makes the scientific community a community. It’s one reason why scientists volunteer to review grants and papers. Perhaps more than in other disciplines, scientists expect their arguments to be heard in full and carefully rebutted. Problems come when they interact beyond the community. Scientists don’t always anticipate that a reporter will sometimes listen to a long, cautious explanation and then use only the most enthusiastic sentence.

This leads to why stem cell researchers and stem-cell research advocates misunderstand each other.

The news that cultured human skin cells had been reprogrammed to an embryonic-like state came in late November of last year. Embryonic stem-cell researchers crowed over the accomplishment: how it advanced understanding of the rules governing cell potential; it promised more-accessible research tools and, maybe, cell therapies. Many embryonic stem-cell-research advocates despaired, fearing that the discovery would give ammunition to those who wish to ban all embryonic stem cell research. Scientists’ enthusiasm went off-message, many advocates chided. Advocates felt betrayed that scientists who reviewed the breakthrough papers hadn’t warned them before publication so they could prepare a media response.

But, for the most part, scientists act to ensure that consensus-building mechanisms are driven by logic; that means saying what they think and taking seriously the promises of confidentiality given during the review process. If advocates convince scientists they must act otherwise to ensure favorable policy, they risk weakening what gives the scientific community, and science, its strength.

Advocates that support scientific research have worked hard and with some success to convince scientists that they must reach out to the general public so that society can value and support their work, but I think lecturing scientists about being “on message” could seed distrust. It would be far, far better and easier for scientists to learn to convey the essential skepticism of their discipline than to learn to convey one particular message.

To me the quintessential scientist is one who says, “I think I’ve found the most exciting thing ever. Now I have to work as hard as I can to see if I can prove it wrong.” Some apparently exciting things really are; some aren't. For most reading this blog, the exciting thing is that cells not derived from embryos can behave like embryonic stem cells; the hard work necessary to know if it’s really true means comparing these cells with embryonic stem cells, that means work with embryonic stem cells to know which cells can answer which questions. That’s not a message; that’s a thought process more people should understand.

I don’t pretend to have any answers for how researchers and research advocates can work together more productively, but I’ve spent the last two nights watching non-specialists and specialists spending their leisure time together, and I think the answer may lie somewhere in that.

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Stem Cells Go to the Movies

Posted on behalf of Brendan Maher, locum Nature biology features editor

Last night I went to the Philadelphia public television station WHYY, to see an independent film on stem cell researcher Jack Kessler of Northwestern University and the sharp turn his research took when his daughter lost the use of her legs after a skiing accident. The movie is called “Mapping stem cell research: Terra Incognita”.

Shot in stark video, the piece paints an intimate portrait of Kessler, his family and his “other” family -- the postdoc and student working on a spinal regeneration project under his direction. The movie is positioned to put a human face on the ethics of embryonic stem cell research. Kessler is an outspoken activist for this kind of work – moreso even than his college-aged daughter, who just wants to get on with her life.

I was more compelled by the personal look at his postdoc and student, as they test the effects of injecting a self-assembling gel matrix into severed mouse spinal cords and see if axonal growth is able to cross a crucial barrier. It’s a live animal follow-up to the experiments presented in this Science paper.

In the movie you see tense lab meetings with negative results, time-consuming troubleshooting, and that odd mistrust that junior researchers feel about their results that is overshadowed by the enthusiasm of a PI. Ultimately, their paper is rejected from Science without review. Not your happiest of endings, but certainly appropriate.

The screening was followed by panel discussion including science journalist Marie McCullogh from the Philadelphia Inquirer; Jonathan Epstein, a University of Pennsylvania stem-cell biologist; and two bioethicists, Paul Root Wolpe from Penn and Catholic priest and biologist, Father Tadeusz Pacholczyk, who appears in the movie comparing embryonic stem-cell research to slavery. Needless to say, it was a heated discussion about the nature of the embryo and the equivocation between potentiality and identity. The roundtable more or less proved that the recent discovery of reprogrammed, or induced pluripotent stem cells, in no way changes the nature of the debate.

The question was raised, but never adequately answered by the main stem-cell opponent in the room (that would be Fr. Tad) whether it would be acceptable to use treatments, if ever developed from these induced cells, based on the fact that they were made possible by research he finds otherwise abhorrent.

The film starts running on US public television stations on 15 January. A listing of screenings around the country is available here.

Cross posted from Brendan Maher on The Great Beyond.
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Shanghai stem cell conference promises more to come

Shanghai crab is a delicacy available for only a short time each year, and the 20-million-strong href="http://query.nytimes.com/gst/fullpage.html?res=9A0DE2D91F3BF937A2575AC0A960948260&sec=travel&spon=&pagewanted=1" > residents of Shanghai devote themselves to its consumption. It was auspicious that the tasty crabs were still available during the first Shanghai International Symposium on Stem Cell Research, attended by around 500 scientists, hundreds of Chinese researchers and close to 100 foreigners. (NOTE: I wrote this on November 10th, but wasn't able to post until today.)

To put that in perspective, the last meeting of International Society for Stem Cell Research, the biggest annual stem cell conference, drew just over 1,900 attendees in June this past year.

China’s government and academies are pouring resources into stem cell research, and Chinese-born researchers trained in the United States are proving a huge asset. Some are returning to China to head up labs in that country; others are remaining in the US but forming collaborations with researchers in China.

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State Controller Recommends Inquiry in CIRM Board Conflict of Interest

Accusations against the chair and another member of California’s stem-cell institute should be referred to the state’s Fair Political Practices Committee, State Controller John Chiang said today at a meeting of the financial committee for the California Institute of Regenerative Medicine (CIRM). A public advocacy group had called for Robert Klein and John Reed to resign after learning that Reed, who is also president of the Burnham Institute, asked CIRM to reconsider its decision that the recipient of a previously awarded grant was not, in fact, eligible for funding because he was not an on-site, full-time employee of the Burnham Institute.
UPDATE on 11/28: Here is the letter from Chiang's office to investigate the charges.
Following Klein’s advice, Reed wrote a letter to CIRM staff in charge of administering the grant stating that David Smotrich, a clinician affiliated with Burnham, should be eligible for the award of $638,000. CIRM staff did not consider the request, and the grant was not awarded.

However, John Simpson of the Foundation for Taxpayer and Consumer Rights said that Reed should resign because, as a member of CIRM’s oversight committee, Reed should not have made requests on behalf of his institution. Simpson also called on Klein, who has no affiliation with the Burnham, to resign, saying he demonstrated poor judgment.

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Stem-cell policy detanglers

A patchwork of stem-cell funders are stepping up to fill the void left by the US NIH, which cannot fund research on new embryonic stem cell lines.

Efforts to cope with this fragmented group are analyzed in a feature by Nature Reports Stem Cells and an analysis by Stanford lawyer Susan Stayn on Chris Scott’s Stem Cell Blog .

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Comments on an American Scientist in Iran

I've had a number of people tell me personally that they've enjoyed reading Rudolf Jaenisch's account of his visit to a stem cell conference in Tehran hosted by the Royan Institute. Some Iranian scientists in America wrote in to say thanks. Also of interest, the US National Academy of Sciences just announced plans to expand cooperation with Iranian research and education centers.
Here's the link to our article.

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Stem cell student bloggers

I wanted to give a quick shout-out to some students today.

William Gunn, at Tulane gives his take on a raft of stem cell papers on his blog, Synthesis.

Raja Anand, in Belgium, has put together an impressive collection of links.

And of course, the frighteningly energetic Attila, whom I've had the pleasure of meeting in person blogs on PIMM.

Now, Red Pill, Chris Scott, California Stem Cell Report, you're all great, but there's a certain energy to students, getting started in a field and sharing what they're learning.

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Renaming the Embyronic Stem Cell Registry recasts debate

The day that President Bush vetoed legislation to expand federal funding for embryonic stem cell research, he also issued an executive order calling for a plan to promote alternate sources of pluripotent stem cells, the details of which were announced today. Like the original executive order, it calls for the NIH Human Embryonic Stem Cell Registry to be renamed the NIH Pluripotent Stem Cell Registry.

The implication is that existing pluripotent stem cell lines are equivalent to embryonic stem cell lines. That’s not true. Many scientists think it could be true someday if current techniques advance, but many believe advancing pluripotent stem cells cannot be done without continuing to study embryonic stem cells.

The plan released today includes a soon-to-be-formalized program announcement to fund grants for research on alternative sources of human pluripotent stem cells including dead embryos, altered nuclear transfer (putting genetic material into an oocyte that will cause it to divide without forming a viable embryo), single cell embryo biopsy, and reprogramming somatic cells. These areas could all prove extremely valuable in understanding disease and testing therapies. Nonetheless, opponents of embryonic stem cell research must acknowledge that if this work is performed instead of rather than alongside work on embryonic stem cells, science will suffer and its fruits could be delayed.

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Australian head of California’s stem-cell institute could help globalize stem-cell research

Just a day after the publication of my article wondering whether the California Institute of Regenerative Medicine (CIRM) could capture a big fish as its leader, CIRM announced that it had hooked a big fish.

News reports (links below) hailed the appointment as a coup. Alan Trounson founded the Australian Stem Cell Centre and helped produce the world’s third test-tube baby. He’s also started companies, including the Singapore-based ES Cell International.

One strength that has not been highlighted is Trounson’s potential to link US scientists with those in the Asia-Pacific region. He has been very active in efforts to found an Asian-Pacific Stem Cell Network, and quite vocal about the advantages that that region has for stem cell research. When meeting with leading stem-cell scientists from around the region in June, Trounson was emphatic in discussing the need for political champions.
See our article here.

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CA stem-cell institute gets temporary president

After struggling to find someone to fill the seat vacated by Zach Hall, CIRM seems to be taking a bit of a breather. They've found someone to take the job as president for six months, at $50,000 a month. Richard Murphy as been a member of CIRM's board, and the head of the Salk Institute for Biological Studies in La Jolla, California. He'll take the reins of the institution set to disburse $3 billion over ten years on September 1.
You can read the CIRM press release here.
I have two initial thoughts. One is that as a former board member of CIRM, Murphy probably has a good idea of how long he can last in that position (juggling peole with different aptitudes and agendas and trying to enthuse without overpromising), which apparently is six months. The other concern is the fact that he will recuse himself from decisions involving San Diego-based institutions, according to the Foundation for Taxpayer and Consumer Rights. I understand the concerns about conflict of interest, but how can the president stay out of decisions for a place so powerful and important in stem cell research, and one he knows well too.. And surely Murphy has friends, colleagues, contacts everywhere and not just the place he's called home? There has to be a more effective way keep corruption amd undue influences out of the public sphere.

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Asia-Pacific Stem Cell Network: Please post your thoughts

Recently, I co-chaired a meeting where scientists made a cogent argument for creating a regional stem cell network. A summary of the meeting will be posted on Nature Reports Stem Cells and circulated as an insert in Nature. I hope that the conversation can continue here.

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International stem cell society hopes to expand further from North American roots

“We’ve gone as far away from Boston as possible to go,” Paul Simmons, outgoing head of the International Society for Stem Cell Research, told sparse attendees at an organizational meeting in Cairns, Australia on June.

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Prop 71 instigator to advise international stem cell society

Bob Klein, largely responsible for the legislation that earmarked $3 billion for California stem cell research, has joined the advisory board of the International Society for Stem Cell Research. The announcement came at the end of a tired town hall meeting that capped sessions of scientific talks.
George Daley, incoming president of the society, said that Klein was going to help ISSCR figure out what its mission should be. He wants to give the society more emphasis on research, and he wants to stop fund-raising every time they want to take on a project. He wants a council that will be very philanthropically involved, he says. Well, it’s hard to imagine a better choice.

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Benefit Science With English Help

My week in Japan drove home the obvious. English-speaking researchers need one major talent to prove themselves: the ability to do science. Non-English speakers need two: science and English. This will be true for the foreseeable future, but the scientific community should take steps to lessen its impact.

Doing so will benefit both English and non-English speakers. If non-English speakers are able to publish more easily, knowledge will be available more quickly, so advances can be quickly validated and adopted by others.

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