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Archive by date: March 2009

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Rebuttal to President's Council criticism of Obama expansion of stem cell research

Last week, ten members of Bush's Council on Bioethics issued a statement criticizing President Obama's lifting of the funding ban on human embryonic stem cell research.The statement, posted by the Hastings Center, is available here. See also our previous post.

In the rebuttal also posted by the Hasting Center, Case Western bioethicist Insoo yun first commiserates with the council's hard work. Then he takes them to task, particularly for implying that Bush's policy enabled research. "To say that the Bush compromise is good enough for American stem cell science is an insult to the researchers and to our fellow citizens," Hyun writes. He also points out that embryonic stem cell research has been and continues to be essential to furthering work on induced pluripotent stem cells and that banning reproductive cloning does not logically require the banning of therapeutic cloning.

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As NIH gains ability to fund embryonic stem cell research, California stem cell institute poised to run out of cash

With the U.S. National Institute of Health poised to fund more grants in both non-embryonic and embryonic stem cell research, the California Institute of Regenerative Medicine hopes to focus on the research that can move the science to treating patients. But it’s set to run out of cash. Both Science and the LA Times have written about this recently (links below)

Last Friday’s issue of Science, described the agency’s quest to sell private bonds so that the Institute could pay out grant funds it has already awarded. As things stands now, CIRM is set to go broke in September.

Constance Holden describes the plans of CIRM leader Robert Klein to sell private bonds, noting that he is more optimistic than several others about the possibilities of success.

The article also quotes James Kovach, head of the Buck Institute for Age Research in Novato, California as saying that he expects state initiatives such as CIRM to survive.

Given California’s financial crisis, an editorial in Monday’s Los Angeles Times questions whether the spending is a good use of money, particularly given the agency’s leadership by Klein.

The leadership and governing structure of CIRM have come under a lot of criticism. Its 29-member board is politically appointed and must include patient advocates as well as high-ranking officials from the institutions most likely to receive CIRM funds. Its plans to give loans and grants to companies have been called both essential and overambitious. The agency has also been praised for taking a leadership role in drafting guidelines and for helping to maintain a U.S. pipeline of stem-cell scientists.
Stem-cells the $3 billion dollar question (subscription required)
US policies on human embryonic stem cells (subscription required)
California against cronyism (subscription required)
CIRM’s search for a president (free online access)
CIRM training grants approved, but awards uncertain (free online access, with links to relevant news stories)

Advocates of state funds point out that, even if NIH is allowed to fund more types of research, it is only able to award a small fraction of the grant applications it receives. They also point out states can still fund research that the federal government cannot, particularly research that creates or destroys embryos. The Dickey-Wicker amendment prohibits funds for deriving new lines from early (about 2-5 day-old) embryos no longer needed by fertility clinics as well as for trying to generate new embryonic stem cell lines genetically matched to an existing individual. (See Embryonic education)

For people without subscriptions, there are more excerpts from the Science article on the California Stem Cell Report.

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President's council on bioethics speaks out against ... the president

Cross-posted from the Great Beyond

Ten members of the 18-member President's Council on Bioethics have criticised US President Barack Obama's recent executive order lifting the restrictions on federal funding for human embryonic stem-cell research.

In their statement, the ten say Obama's order is "a step backward" with regards to "the progress that had been made in reconciling the needs of research and the moral concerns of many Americans". Obama's order reversed a policy put in place by George W. Bush in August 2001, which permitted federal funding for research on human embryonic stem cells, but only on cell lines that had been derived by the date of his speech.

Much of the dispute centers on the source of the embryos that could be used for such research. Obama's order does not specify the source of the embryos: whether they are leftover embryos from in-vitro fertilisation clinics, or are created for the purpose of research. This is the source of much of the council criticism. The story has been picked up predominantly by the conservative press (Weekly Standard).

The statement did not come from the council itself, but rather from ten of its members speaking out on their personal beliefs. The council, created in its current form by Bush in 2001, has come under fire before, for instance in 2004 when one of its members was dismissed after speaking out against Bush's stance on stem-cell research (Nature). The council in its current form is constituted through 30 September 2009.

Posted by Alex Witze on March 27, 2009
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Human iPS cells without genetic integration: Six reprogramming factors, a plasmid, and a holy grail

For the first time, human skin cells have been reprogrammed to pluripotency without requiring genetic elements to insert themselves into the reprogrammed cells. Though so-called induced pluripotent stem cells promise to be as powerful as embryonic stem cells in their ability to differentiate into all cell types, standard techniques use viruses to insert multiple copies of reprogramming genes into the cells; this makes the cells less predictable, and it creates a higher risk of a cancerous growth. As a result, many laboratories have been racing to publish techniques to reprogram cells without permanent genetic modification.

The latest paper, by Junying Yu and James Thomson at the University of Wisconsin–Madison, and colleagues, uses a plasmid that does not integrate into chromosomes to reprogram the cells[1].

Continue reading "Human iPS cells without genetic integration: Six reprogramming factors, a plasmid, and a holy grail" »

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Comments on two previous posts

Lee Buckler has pointed out on my business round-up that the merger between reagents-and-animal-cells company Stem Cell Sciences in the UK and the cell therapy company StemCells in California creates a single company with near-term, medium-term and long-term sources of revenue. That makes sense to me, even though the differences in technologies and the geography seem hard to manage. Also, he just posted a very comprehensive round-up himself. You can see them here.

William Gunn has just commented on my clinical trial analysis post that it’s not just bone-marrow transplant that might call themselves stem cell tranplants but consist of poorly purified and characterized cells. Neural cell transplants can go the same way. Good point. The most salient example I can think of was the tumours that grew in a young patient’s brain and spinal cord after an unregulated procedure (See our Commentary by Clive Svendsen and my news story ). But, like Gunn points, out, it is also a worry for clinical trials.

Thanks both for your insights.

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Stem-cell business round-up

Here’s a collection of some stem-cell business news in March.

Two companies selling stem cell products for laboratory research have announced a deal. According to Fox Business, Stemgent is going to start marketing CellDesign’s kits to differentiate adipocytes.

Just a couple weeks ago, Stemgent announced that it had received $14 million in venture capital from firms including HealthCare Ventures and Morgenthaler Ventures. Stemgent sells a range of products for growing and differentiating pluripotent stem cells, particularly small molecules that influence cells’ fates. Also recently, CellDesign announced that it was selling two lines of adipocyte stem cells.

Meanwhile, Invitrogen has launched a product to push DNA and RNA into a wide variety of mammalian cells. (The fact that they mention stem cells in the title of the announcement gives an indication of where they think their market is and where it will be growing, I think.)

The UK’s Epistem has signed a deal with Novartis to use epithelial stem cells to find drug targets. It’s $4 million upfront, with up to $45 million in potential milestone payments. How does this compare with other deals? I tried looking up a few. Some announce milestones, such as Cellartis with Novo Nordisk. Other deals, like Novocell with Pfizer and Roche with Cellular Dynamics International, don’t mention. I’m sure somebody has thought of this more deeply than I have, but it doesn't seem to correlate (as I would have guessed) with whether the cells are used as therapies or as screening tools. Please comment.

A lot of people in the business realm expect a spate of mergers between stem cell companies. We saw Jamie Thomson’s companies come together in November. Cellular Dynamics International, Stem Cell Products Inc. and iPS Cells Inc are all one in CDI.
I seem to have been the only person in the world surprised that cell-therapy company StemCells, Inc merged with Austin Smith’s reagents company Stem Cell Sciences. I figured each could find a more-similar company to merge with, but the goal, it seems, is diversity. StemCells is in California and is testing fetal neural stem cells in children’s neurodegenerative diseases. Stem Cell Sciences is in the UK, has reagents that keep stem cells from differentiating, and also has intellectual property on rat embryonic stem cells.

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More analysis on stem cell clinical trials

In response to my last post, I wondered what Chris Scott's analysis of clinicaltrials.gov would say if he looked for fetal stem cells. He just told me he did the relevant search, and came up with nothing. In fact, one trial by StemCells that does use fetally derived cells does not say so in its clinical trial description. (See his post and several interesting comments at the link above.) Christopher Scott directs the program on stem cells and society at Stanford.

Scott has told me before that he is concerned that, because of enthusiasm for stem-cell research, clinicians may be including the term “stem cell” in clinical trials even if what’s being transplanted are poorly purified and characterized mixtures likely to contain stem cells. When I asked him about his recent analysis, he said he couldn't prove whether or not stem cells had been carefully purified or characterized. "It's just that the words "stem cell therapy" sounds sexier than "cell therapy" which is more accurate because most studies transplant populations of cells "enriched" for stem cells."

I suppose similar PR reasoning can explain the dearth of "fetal stem cells" in the database. A more charitable explanation would be that, of course, fetal stem cells is as poor a descriptor as is adult stem cells, since fetuses have already formed all their major organs. All the trials I know of using fetal cells use fetal neural cells. (But see my last post for more on that.)

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Clinical trials mentioning stem cells up over 200% from summer 2007

The number of U.S. registered clinical trials using stem cells increased from 709 at in summer 2007 to 2,319 today. For trials using stem cells in heart disease grew by 110% last year (from 118 to 56); Parkinson’s disease fell by 100% last year (from 1 to 0). That’s according to an index of clinical trials just posted by Stanford’s Chris Scott.
Scott examined used the world’s largest registry of clinical trials to see how many included the term stem cells, categorized them, and then compared results between two years. Not surprisingly, the vast majority of trials were in hematology and oncology indications, for which bone marrow transplants, which contain stem cells, have been practiced for generations. One comment notes that as little as 5 years ago, all such trials would have fallen under that indication.
Scott offers caveats for his analysis. In particular, not every hit in a text search need be real. Nonetheless, the numbers are fascinating.
One category the analysis does not explore is trials using fetal stem cells. Those that I know of are all for neurological indications, and at least three have received or asked for regulatory approval to start trials within the twelve months. (The trials that have been given the green light are StemCells and ReNeuron.)
Given reports that a boy developed tumours in his brain and spinal cord after an unregulated (and highly criticized) stem cell procedure, this would be an interesting category to watch. In fact, just days after the reports came out, the FDA told NeuralStem to put its plans for a clinical trial on hold.

As research on all types of stem cells grows, it will be very interesting to see how the mixtures of cell types and indications studied shifts.

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Stem-cell tourism, what's a scientist to do?

Members of the scientific community should lobby regulatory authorities to regulate bogus stem-cell clinics, according to the latest policy forum in Science this week (subscription required). The piece calls out the claims and (lack of) evidence put forward by stem-cell clinics in countries “not known as leaders in biomedical research.”

The forum also urges the World Health Organisation to create a consensus statement on the clinical application of stem cell research. Individual scientists should help provide non-English translations of existing information, such as the patient handbook developed by the International Society for Stem Cell Research, which includes questions would-be stem cell tourists should ask clinics and physicians.

The authors of the forum, Doug Sipp of Japan’s RIKEN and Kyoto University and physician Sorapop Kiatpongsan of Chulalongkorn University of Bangkok and Harvard, published an earlier commentary with Nature Reports, in which they analysed the duties and motivations of patients, physicians, scientists, governments, and other stakeholders that act in this arena.

Though stem cell tourism operates outside the scientific mainstream, stem-cell scientists should care about it not just because patients can be harmed but because mishaps can cause mistrust of those clinicians who are struggling to meet regulatory requirements and established guidelines to move stem cell research to the clinic.

Here are some of our articles reporting on stem cell tourism and the scientific community’s actions and reactions toward it.

Stem cell researchers face down stem cell tourism
A variety of international efforts hope to warn patients off unregulated treatments

Stick to the guidelines and fewer get hurt
The ISSCR hopes its handbook will prompt regulators and governments to shut shady clinics

Unregulated stem cell transplant causes tumours
Researchers say cells were poorly characterized prior to transplantation

Stem cell clinical trials must be closely monitored
Results of unregulated stem cell transplant were predictable and avoidable

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Can gene therapy plus liver "stem cells" cure diabetes?

The press resleases of two new studies are making the rounds, so I'll point to them here. One mouse study, published in Developmental Cell, shows that gene therapy can prompt liver cells toward beta cells. I'll cover the other press release tomorrow.


I'd actually looked into the mouse study a bit, so I'll put that up now. It will go on the site as a formal article next week.
A sort of beta-cell magic: transdetermination seems easier than transdifferentiation
A single added gene prompts liver progenitor cells to make insulin and reverse diabetes

With the introduction of a single gene, cells in the liver can take on the function of pancreatic cells and go on to reverse symptoms of diabetes in a mouse model of the disease. Researchers led by Lawrence Chan at Baylor College of Medicine in Houston, Texas had already shown that they could, in effect, cure diabetes in mice by infecting their livers with a virus containing the gene for neurogenin (Ngn3), a transcription factor that is expressed as cells begin differentiating into insulin-producing beta cells, the type of cells lost in juvenile diabetes. But while the researchers knew that it worked, they did not know why, so they began trying to figure out what cells in the liver began producing insulin.
Careful lineage tracing studies implicated two types of cells.1 The first were hepatocytes, mature cells that made insulin only for about six weeks after infection. The other, more-stable source of insulin-producing cells were liver progenitor cells. These actually switched lineages and went on to form clusters of islet cells that resembled those that the pancreas would make normally after an injury. Further analysis showed that the liver cells were expressing a wealth of genes made in pancreatic lineages in general and for the insulin-producing beta cells in particular.
“The phenomenon is certainly worth further investigation,” says Ken Zaret, a cell biologist at the Fox Chase Cancer Center in Philadelphia. He says that Chan’s work is similar to that of other researchers who showed that adding genes for transcription factors can change cell differentiation.2,3 “However, it differs in discovering that the more stable target in the target tissue is not the terminally differentiated cells, here the hepatocyte, but rather an apparent facultative progenitor cell.”
Chan believes that fully developed hepatocytes are not capable of transdifferentiating, or switching from one mature cell type to another. However, the progenitor cells are at a “weak point” in their differentiation pathway, in which their default lineage can be transdetermined to another lineage. Liver and pancreas are both endoderm organs, and some molecules expressed early in their development are the same. “I believe that the more closely the cells are related to the endocrine pancreas lineage, the more likely they will be ‘pushed’ into the beta-cell lineage,” Chan explains.
Several factors may be doing the pushing. “My sense is that the success of the experiments is due to the convergence of multiple stimuli,” says Zaret. In addition to the Ngn3 transcription factor, he says, other conditions, particularly the viral infection and the high blood glucose levels in diabetic mice could be necessary to stimulate the nascent beta-like cells to proliferate.
Chan believes that this approach of causing progenitor cells to switch lineages may have more general applications. “Induced transdetermination may be easier to accomplish than induced transdifferentiation, if one can identify the receptive cell lineage,” he says. Thus, “receptive” progenitor cells could be a viable target to regenerate organs in multiple diseases, including but not limited to diabetes.

Related articles

Smash the (cell) state

Thomas Graf: Cellular identity and transdifferentiation


1. Yechoor, V. et al. Neurogenin3 is sufficient for in vivo transdetermination of hepatic progenitor cells into islet-like cells but not transdifferentiation of hepatocytes. Developmental Cell (2009)

2. Lassar AB, Paterson BM, Weintraub H. Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell 47, 649-56 (1986)

3. Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455, 627-32 (2008)

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With NIH back in the game, CIRM leans toward translation

Cross-posted from The Great Beyond

Obama’s decision made scientists cheer, but raised a question for CIRM: how would its leaders make the case that the agency is still necessary – especially when the state is trying to crawl out of a fiscal crisis? The California voters created CIRM in 2004 in part because the federal government wasn’t funding much human embryonic stem cell research. But with the hands of the National Institutes of Health no longer tied, long-time critics have said CIRM should “adopt a secondary role to NIH” or even close shop entirely.

In response, CIRM is repositioning itself more firmly as a translational agency, preparing for NIH to take on some of the burden of funding basic research. At its 12 March board meeting, the agency reordered some of its programs and cut or delayed funding for others to ensure that the agency will have enough money to support its clinically focused disease team grants, which are expected to be awarded this fall.

CIRM will run out of money this September because the state’s fiscal crisis stopped bond funding from flowing to the agency. The state has authorized CIRM to sell up to $400 million in private bonds to fill the gap. The board members were asked to vote on recommendations prepared by CIRM staff on ways to cut back on expenses in anticipation that $100 million of these bonds will be sold this year. The board endorsed some of the CIRM staff’s recommendations, including funding one set of grants that it awarded in January – $17.5 million to train undergraduates and master’s level students to work with stem cells – and delaying funding for twelve months a second set of grants awarded in January that will give $40.6 million to graduate students, postdoctoral and clinical fellows already working in stem cell research labs.

But the board also voted to rejigger a list of priorities drawn up by CIRM staff. The board’s vote lowered the priority of a set of basic biology grants that were to be awarded this year and boosted the priority of part of the funding for the disease team grants, which will be worth a total of $210 million.

The move protects the full amount of funding for the disease team grants, potentially worth up to $20 million apiece, which will be given to 10 to 12 groups of scientists that aim to put stem cell-based therapies into clinical trials within four years. The disease team program is designed to be a jewel in CIRM’s crown, demonstrating the agency’s special role in translating stem cell science into treatments. The move to prioritize the grants came after patient advocates on the board argued that federal funding can now flow to basic biology research: “The NIH funds that [basic] work,” said board member Joan Samuelson of the Parkinson’s Action Network.

CIRM chief communications officer Don Gibbons said the board’s action answers the critics who said that Obama’s policy change has made the agency less necessary: “This action shows that, yes, there is a place for CIRM, and we are doing something different from NIH,” Gibbons said.

The board also voted to elect two vice-chairs: current board member Duane Roth and California Democratic party leader Art Torres. Torres will draw a $75,000 salary, far less than the $332,000 salary discussed last fall, when CIRM drew some flak for awarding board chair Robert Klein a $150,000 salary on the same day that Governor Arnold Schwarzenegger warned that the state was facing “financial Armageddon”.

CIRM President Alan Trounson had the day before the board meeting endorsed the idea that CIRM should carve out a special role for itself as a translational research agency. “Wouldn’t our natural niche be somewhere between the basic science and the clinic? I think this is where we should be,” Trounson said at an 11 March meeting in San Francisco meeting to discuss the future of the agency.

But some scientists at that meeting were worried by that idea. “This push of getting out there to the clinic has some risks,” warned Arnold Kriegstein of the University of California San Francisco at the meeting. “There’s a risk that little will be learned at great cost” if patients are harmed in poorly designed early clinical trials, Kriegstein said.

And Warner Greene of UCSF’s Gladstone Institute of Virology and Immunology cautioned against “turning over the reins” of basic science to the NIH: “It’s foolish to expect now that the disease teams will succeed,” he said.

CIRM chief scientific officer Marie Csete sought to ease such fears at the 11 March meeting: “We are not abandoning basic science,” she said, adding that any CIRM-funded clinical trials will proceed with caution. “No one wants another name like Jesse Gelsinger in this field,” she said, referring to the 18-year-old who died in 1999 as a result of his participation in a gene therapy trial.

But, Csete pointed out that CIRM has “a shorter timeline” than the NIH,” and feels a special responsibility to California taxpayers who created CIRM hoping to get a real return on their investment. “First and foremost, we want to get to the end goal, which is cures,” Csete said.

by Erika Check Hayden
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Neural clustering

Here’s a trio of three early stage studies that look encouraging for using stem cells as therapies in the brain.

Continue reading "Neural clustering" »

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Obama’s stem-cell orders, the next-day stories

On Monday, President Obama lifted federal restrictions on funding human embryonic stem cell research, just in time for scientists to apply for NIH grants in stem cells and regenerative medicine.

The Washington Post has a very nice collection of articles, including transcripts of Obama’s speech and a Q&A with Harvard’s David Scadden, and an analysis of the key questions Obama’s order leaves to the NIH. One link can lead you to all the rest.

The New York Times reports that stem-cell researchers won’t be flush with cash, even in California, and examines financial woes at the California Institute of Regenerative Medicine.

The most chipper story, titled “Life injected into Bay Area stem cell companies”, is from the Contra Costa Times.

It includes an anecdote from Michael West, who helped found stem cell companies Advanced Cell Technologies and Geron. West recalls a conversation with Bob Swanson, founder of biotech superstar Genentech.

“"I remember he pulled me aside and told me that stem cell research is going to be just like recombinant DNA was for the industry," West said. "Once the political cloud was lifted, the industry just exploded."

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More ES-cell research could pave way for less ES-cell research

Just last week, three labs reported on two techniques to reprogram human cells without permanently inserting the viral genes normally necessary to render cells pluripotent. At least one headline proclaimed that ES cells were obsolete.

If that were the case, one would expect yesterday’s move by President Obama to allow funding for more embryonic stem cell lines to be greeted with a yawn. It wasn’t. The removal of the funding ban made headlines both Friday and Monday. The International Society for Stem Cell Research characterized its scientists as ‘elated.’ Many scientists saw it as the end of a lost almost-decade of research progress.

US News and World Report has rounded up much of the coverage. See Nature’s coverage here.

Scientists are flooding into the race to reprogram adult cells to behave like embryonic stem cells (i.e. to make induced pluripotent stem cells), but they need embryonic stem cells for comparison.

James Thomson of the University of Wisconsin, the first researcher to derive human ES cells and one of the first to make human iPS cells, told me that with the new presidential policy, the newer ES cell lines will replace those made back before scientists had optimized the procedure, back when scientists were trying to figure out whether making human ES cells was possible at all.

“The way I grew them originally was pretty bad,” Thomson told me. “You would pick out the couple [attempts] that grew and passage them [treat them so they can multiply in culture]. The real gold standard will be cells that have been made under better conditions.”

And of course, the study of ES cells was what made the production of iPS cells possible at all. It was necessary to determine what genes could be used for reprogramming as well as the conditions in which reprogrammed cells could grow.

Scientists study the cells they believe are best able to answer their questions (and, at least in the US, they follow ethical guidelines put out by the National Academies). Already, the number of new ES cell lines being made is dwarfed by the number of iPS cell lines. While there will probably always be some questions that ES cells, and no other cell types, will answer, many scientists believe that the field will, of it’s own accord, move more and more toward iPS cells.

Those who want ES cell research to stop now should argue their case on moral, not utilitarian, grounds. The utilitarian argument is best answered by the scientific community.

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Obama poised to lift stem-cell restrictions

Cross-posted from The Great Beyond on behalf of Erika Check Hayden.

Stem cell researchers may have to wait no longer: President Barack Obama appears ready to lift the ban on U.S. federal funding for research on human embryonic stem cell lines created after August 9, 2001.

The ban was put in place by President George W. Bush, who was responding to concerns among abortion opponents that research on human embryonic stem cells is morally problematic because it involves destruction of embryos. Obama will reportedly sign an executive order overturning the ban on Monday, 9 March. The Washington Post also reported that Obama will likely “simply lift the restriction without caveats and let the [U.S. National Institutes of Health] work out the details.” The NIH is currently formulating ethical guidelines and policies that scientists for scientists who want to apply for federal grants to work with human embryonic stem cells.

Obama’s action comes after research advocates had expressed concern over what they considered Obama’s delay in meeting his campaign promise to overturn the ban. “Obviously, we have concerns and would like to see this done,” Tony Mazzaschi, interim chief scientific officer at the Association of American Medical Colleges in Washington DC told Nature last month.

There has also been extensive discussion about whether the ban should simply be overturned by executive order, or whether the job should be done through legislation that would prevent more flip-flops on stem cell policy under future presidents. Now it appears the ban will be overturned both through Obama’s expected executive order and through legislation, as lawmakers have already introduced bills to undo the ban. Similar bills have previously been passed by Congress, but were vetoed twice by Bush; they would likely be signed into law by Obama if Congress passed them again.

Now, scientists are excited at the chance to undo what they see as political interference that has slowed a promising area of research. Human embryonic stem cells can turn into any cell type in the body, making them potentially powerful tools for investigating disease, and possibly treating it. “I feel vindicated after eight years of struggle, and I know it's going to energize my research team,” George Daley of the Harvard Stem Cell Institute and Children's Hospital of Boston told the Associated Press.

Daley and other researchers have been excited by the development of human induced pluripotent stem cells (iPS cells), which have many of the properties of stem cells yet seem less ethically problematic because they are made from adult cells, such as skin cells. Yet they have also cautioned that the cells are not exactly the same as embryonic (ES) stem cells, so there is still a need to continue both lines of research.

“At this point we clearly still need ES cells,” Konrad Hochedlinger of Harvard Medical School in Boston, Massachusetts, told Nature last fall. “It is unclear to what extent ES cells and iPS cells are really equivalent to each other, and showing this will require much more work.”

More stories: New York Times, BBC, and many others. And stay tuned to nature.com/news for more in-depth coverage from Nature.

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Reports: Obama to lift ES cell funding ban Monday morning

After a lot of wondering about when it would happen, several news outlets are announcing that President Obama will overturn restrictions on funding human embryonic stem cell research on Monday morning, still within 50 days of his taking the oath of office. Some pundits had expected Obama to lift the restrictions within the first days of his presidency, feeding speculation that Obama wanted federal funding for the research to be authorized by Congressional authority.
Here's the story from the Washington Post. The discussion of the topic on CNN touted that it was bipartisan.

It will be interesting to see if this changes the grants that the NIH can offer in its Challenge grants governing stem cells.

Here's Reuters, which says that details are sparse but will include general measures to increase scientific integrity in the administration.

See links to previous coverage on this blog.
What's Obama waiting for?
News round-up: Obama and the funding ban.

Here's a comparison between how the UK, Germany, and US have pursued policies around human embryonic stem cell research.

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What a week for iPS! Human cells reprogrammed with genes that can take their leave

The bogey of making cells that behave like embryonic stem cells has been genetic engineering: so far, reprogramming human cells has required permanent genetic modification, a fact that raises worries of increased cancer risk and unpredictability.
Three prominent papers this week describe reprogramming cells without permanent genetic baggage. They use genetic material that gets into cells, reprograms them, and snips themselves out.

Work published Sunday in Nature dispensed with viruses and instead engineered a transposon called piggyBac to take itself in and out of the cells. That work was led by Andreas Nagy, of Mount Sinai Hospital in Toronto, Canada, and Keisuke Kaji, of the University of Edinburgh, UK. (See Virus free pluripotency for human cells ) On Thursday, a paper by MIT’s Rudolf Jaenisch published in Cell took the cells much further (See Test tube disease models one step closer.) They reprogrammed cells from five patients with Parkinson’s disease and then showed that these reprogrammed cells could be differentiated into neurons. They use an engineered virus that snips out the integrated reprogramming genes once the cells have transformed. Though it leaves behind some remnants of the virus, it removes potentially dangerous genes. Perhaps more importantly, the iPS cells from which the reprogramming genes have been removed behave more like embryonic stem cells.

As Nature’s Erika Check Hayden reports: “While 48 genes were expressed differently between the factor-free iPS cells and the embryonic stem cells, 271 genes differed between the factor-free iPS cells and the iPS cells that retained the factors.”

Though the work is exciting, the race is still on for new techniques to derive iPS cells. The holy grail is to transform the cells without using DNA at all, presumably by adding small molecules and proteins that cause adult cells to reactivate their own, silenced version of pluripotency genes.

Though the cells appear to be very, very similar in their undifferentiated state, and mouse iPS cells can contribute to all tissues in a chimeric mouse, researchers warn that the mechanism by which cells are reprogrammed is not fully understood. The next steps are to study cells differentiated from both ES and iPS cells to see which would be best for cell therapies and drug screening.

Integration-free iPS cells describes other DNA-based techniques to reprogram cells without permant genetic modification.

Cells reprogrammed using only one gene describes a recent paper using proteins and small molecules to reprogram cells and includes links to several related research highlights.


For lay coverage of the self-excising reprogramming factors, see the LA Times , which covers all three papers, the New York Times, which covers the Jaenisch paper and has a nice description of the Jaenisch construct, and the Washington Post, which covers the transposon papers and how techniques to make pluripotent stem cells without embryos might impact political battles over the funding of ES cell work.

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Stem cell bill to be re-introduced

Senators Tom Harkin and Arlen Specter are expected to reintroduce the Stem Cell Research Enhancement Act, legislation to lift the Bush Administration's restrictions on funding stem cell research.

The blog Pennsylvania Avenue quotes speculation that the stem-cell research bill, cosponsored by two Republican sponsors and three Democratic sponsors could lead to a quick bipartisan victory. The Senators are, as reported by American Chronicle, Dianne Feinstein (D-CA), Tom Harkin (D-IA), Orrin Hatch (R-UT), Ted Kennedy (D-MA), and Arlen Specter (R-PA).

A very short piece in the New York Times identifies the legislation as the same one vetoed by President Bush. That means the Representative sponsors of the legislation are Mike Castle and Diane DeGette. That was vetoed twice by Bush; it’s second time up was covered here.

Just prior to announcments that this legislation was imminent, Meredith Wadman’s article in Nature explored the notion of whether Obama would want Congressional action to accompany his lifting of stem cell policy. See that and related articles here.