The Niche

The excitement from the reprogramming and cloning breakthroughs from earlier this month is fading, and people are looking to future paths and profits. Monkey cloner Shoukhrat Mitalipov has teamed up with a start-up company in San Diego, though it’s not exactly clear what it will be doing. Reprogramming cells without eggs or embryos will require less money, skill, and hard-to-procure material, so expect both academics and entrepreneurs to jump into the space. I’ve already seen one stem cell company touting the advance in a press release.
The intellectual property field may be more open as well. One of the teams that reprogrammed human skin cells was led by James Thomson of the University of Wisconsin, who also led the first team to generate human embryonic stem cells from leftover embryos provided by an IVF clinic. His patents covering human embryonic stem cells are controlled by WARF (Wisconsin Alumni Research Foundation) and have raised howls of protest from the community. Thomson says the intellectual property surrounding reprogramming techniques will "be complicated." When I asked WARF what that meant, I was told that the patent situation is complex because two groups made the discovery at the same time and the science is moving very rapidly. Another complicating factor is that the two groups used different techniques to reprogram cells, and whispers of forthcoming techniques are growing into shouts.
That doesn't yet mean patient advocates should be dancing in the streets. To keep us levelheaded, Newsweek’s Sharon Begley has an article that’s informative and easy to read. Also, while several prolife blogs are hoping the end is nigh for embryonic stem cells, the scientists leading the egg-free reprogramming breakthrough are making a strong case that studies of embryonic stem cells hold the keys for using these so-called induced pluripotent cells. See an editorial in Nature and this article from AFP.
For what it’s worth: Of the articles that appeared at the time of announcement, I particularly enjoyed the articles from Bloomberg , Nature, and Science.

Posted by Monya Baker on November 29, 2007
Categories: Reprogramming/Pluripotency | Permalink | Comments (0) | TrackBacks (0)

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.

Continue reading "State Controller Recommends Inquiry in CIRM Board Conflict of Interest" »

Posted by Monya Baker on November 27, 2007
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That’s a paraphrase of what James Thomson at the University of Wisconsin-Madison told reporters at a press conference this morning when he announced that he’d induced human skin cells to take on the trappings of embryonic stem cells. His work is published online today in Science. Tying (or narrowly beating) Thomson is Kyoto University’s Shinya Yamanaka who reports his accomplishment in Cell. A news article from Nature is available here.
Thomson said that other researchers would be hard-pressed to distinguish his cells from human embryonic stem cells (ESCs) but repeated several times that whether these cells differ from ESCs in important ways remains to be seen. It does seem, however, that highly flexible cells could be made without collecting eggs from women and without destroying an early stage embryo.

Moreover, these pluripotent cells could be made from patients with known diseases. If the root causes of disease were genetic that could be a better way to study disease. It could also mean that replacement tissues for, say, diabetes patients using genetically identical cells. Thomson predicted that this research could lead to researchers testing drugs in ‘panels” of cell lines to figure out if toxicity and efficacy varied across genotypes.

Both Yamanaka and Thomson used a suite of four genes to transform cultures of skin cells. Both quartets included OCT3 and SOX2, well known markers of pluripotency. For the other two, Yamanaka used the KLF4 and c-Myc, which he’d shown earlier in mice. Thomson used NANOG (identified a few years ago as a master switch of pluripotency) and LIN28, implicated in processing mRNA. (According to a news article by Science.)

Besides these groups, there are many, many whispers of others about to publish similar accomplishments. Some report overcoming a remaining drawback: the transformed cells contain multiple copies of genes inserted into the genome by engineered viruses. “Nobody thinks we’re going to have those vectors even a year from now,” Thomson told reporters who had called in.

But he said, the major barriers still exist. The manipulations move cells back to what he called “a ground state” but for therapies and drug screening, researchers need a differentiated state. That was something he said was coming.

Synergies with other research

Thomson said that the time, cost, and expertise needed to make embryonic stem cells would likely push researchers to prefer genetically reprogrammed cells. Induced pluirpotent cells made by Yamanaka and Thomson come directly from cultured skin cells. Embryonic stem cells are made by scooping out cells from within an embryo and culturing them. Both types of cells can form teratomas and be differentiated into other cell types. Embryonic stem cells can also be made from cloned embryos, in which the nucleus of a differentiated cell is placed in an oocyte that is then activated to divide to form an embryo.

That feat was never been accomplished in humans (earlier reports were fraudlent). Nature did report it this week.

Thomson said that it would be useful to reprogram cells from the same monkey whose nucleus was used to make the embryonic stem cell lines. Then, cells generated from oocyte-assisted reprogramming and genetically engineered reprogramming could be compared directly.

Much of the speculation about what would need to happen to make the technique useful was reported when Yamanaka and other groups reported the accomplishment in mice. Here is a link to that article .

Posted by Monya Baker on November 20, 2007
Categories: Cloning, Reprogramming/Pluripotency | Permalink | Comments (2) | TrackBacks (0)

This week, Nature released a paper reporting the first embryonic stem cells made from an embryo cloned from an adult monkey. Next week, researchers in the UK hope to try the same thing with humans. The Oregon-based monkey team needed just over 300 monkey oocytes to make two monkey embryonic stem cell lines. The researchers at the University of Newcastle upon Tyne expect to have twice that number of freshly collected oocytes from women seeking fertility treatments.

They are absolutely not trying to clone a live human. Instead, they will remove the chromosomes from an egg, insert the nucleus of a cell from another person, and stimulate the egg to divide. If all goes as they hope, the egg will form a hollow-ball shaped embryo called a blastocyst, from which the cells to create embryonic stem cells will be collected. (The process will destroy the embryo.)

There are plenty of teams in the US working on the tecnhique. James Byrne, lead author on the recent Nature paper reporting nuclear transfer in monkeys, has joined Rnee Reijo Pera's lab at Stanford. Kevin Eggan at Harvard has his own techniques to apply to human. But these groups have to work with frozen embryos or oocytes otherwise not deemed suitable for implantation.

Shoukhrat Mitalipov, who led the work in monkeys, is working with Mary Herbert’s team in the UK. He would like to attempt the procedures himself at the Oregon Health and Science University, but before that could happen, his institutional review board would need to formulate a policy that would allow researchers to collect eggs and he would need private funding to carry the work out. Regulatory policies in the UK allow researchers to pay for half of woman’s fertility treatment if she provides half of the collected eggs for research, and there is currently a waiting list of women hoping to provide eggs, says Herbert. In fact, the waiting list is growing because of the publicity received.

In the US, such arrangements are often considered compensation. Instead, researchers can ask women to undergo the exhausting and somewhat risky procedure for altruistic reasons. In the UK, research on monkeys is highly regulated and so the research that worked out a successful procedure for cloning primate cells would have been hard to do, says Mitalipov.

What a strange world, where international collaborations depend (at least partly) on differences in local attitudes.

Standford University's Chris Scott has some relevant posts on his stem cell blog.
His take on monkey stem cells is here.

His analysis of the UK versus US egg-sharing situation is here.

Posted by Monya Baker on November 15, 2007
Categories: Cloning, Policy | Permalink | Comments (1) | TrackBacks (0)

Patient-specific stem-cell lines now seem more likely than before, thanks to the discovery that primates' genomes can be reset to the primoridal state to sustain embryonic stem cells. Researchers at Oregon Health and Science University transferred the nuclei from cultured skin cells from an adult male monkey into 304 enucleated egg cells. They were able to coax 35 of these into blastocysts. They scooped out cells from 20 of the best blastocysts to make 2 stem cell lines carrying the same chromosomes as the male monkey (one line was genetically abnormal). The efficiency of eggs to blastocysts is much improved, but the overall efficiency is low. More work needs to be done.
“I’m delighted to hear this,” says Jose Cibelli of Michigan State University of the accomplishment. “But that's still too low to be justifiable for humans."
This work was first announced at a conference in June. It is now set to be published in Nature next week, as David Cyranoski reports. Not only did this paper go through the standard, rigorous peer-review, Nature also asked outside experts to carefully examine the cells to make sure they really had been produced through somatic cell nuclear transfer. That's because the stem-cell world has been rocked by fraudulent research. The rationale was explained further in an editorial in Nature.
Next week, Nature Reports Stem Cellswill have a longer story on the factors that led to success as well as an Inside the Paper revealing anonymous comments of the scientific experts who reviewed this paper.

Posted by Monya Baker on November 14, 2007
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Chris Scott, who researches ethical and legal issues involving stem-cell research at Stanford had this to say about Jeanne Loring's recent commentary on Nature Reports Stem Cells.

Jeanne Loring's commentary on the WARF patent situation is an insider's look at the motives and arguments for challenging one of biology's most contentious and important set of patents. Her statements, "WARF has tried to get the same patent issued in multiple countries and failed. Other countries have not even allowed patenting of human ES cells," give clues to the complexity of the international scene. In the EU, legal challenges to hESC patents can center on ethical, rather than technical arguments. Invoking so-called "morality clauses" contained in the European Union's 1998 Directive on Biotechnological Inventions, some jurisdictions and agencies (including the European Patent Office and the German Intellectual Property Office) rule unpatentable any invention that results from
the uses of a human embryo "for industrial or commercial purposes."
But other countries do not. The United Kingdom, for example, has granted patents using hESC lines to a number of for-profit and academic institutions. Sweden has issued one such patent. Even the EPO itself has been inconsistent in its rulings.

Therefore, the situation in Europe is quite fluid and not monolithic, because individual nations can interpret the Directive's language in ways that are consistent with national frameworks of values and beliefs. As the US challenge unfolds, the enemy (or ally, depending on your point of view) is time. Patent reexaminations can take years to resolve. Here, time may favor the patent holders.

Posted by Monya Baker on November 14, 2007
Categories: Intellectual property | Permalink | Comments (0) | TrackBacks (0)

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 .

Continue reading "Stem-cell policy detanglers" »

Posted by Monya Baker on November 01, 2007
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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.

Posted by Monya Baker on November 01, 2007
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