The Niche

Cross-posted from the Great Beyond

The New York Empire State Stem Cell Board (ESSCB) has approved the use of state funds to compensate women who donate eggs for embryonic stem cell research.

The board, which implements New York’s $600 million stem cell research initiative, reached the decision on 11 June. Board members noted that taxpayer funds are already used to compensate some egg donors in state-subsidized in vitro fertilization programs. They also emphasized that researchers in other states that do not allow payment for eggs – including Massachusetts and California -- have largely failed to recruit donors.

Nevertheless, the decision sparked a predictable outcry from activists. The New York State Catholic Conference called it “a grossly unethical, dangerous and exploitative move that treats women’s body parts as commodities,” (Catholic Courier) and Thomas Berg, a Catholic priest and a member of the ESSCB’s ethics committee, criticized the board for not allowing public comment on the issue (Christian News Wire).

See also Nature news: Egg shortage hits race to clone human stem cells

Posted by Monya Baker on June 17, 2009
Categories: Cloning, Ethics | Permalink | Comments (2) | TrackBacks (0)

“Now we have the technology that can make a cloned child” reads the headline of the most-read article in the Independent right now. But the article does not actually break any news, nor does it use the common method of cloning; rather it discusses a well-understood implication of that recent reprogramming breakthroughs might yield yet another weird way of making a baby.

If a technician wanted to do this, here’s how it would work: First, cells would be gathered from an existing human, probably through a skin biopsy. Second, these cells would be reprogrammed to an embryonic like state. (Current techniques to do this require engineered viruses to insert copies of genes into the reprogrammed cells. This makes the cells’ behavior less predictable and more prone to form tumours, but many scientists believe that new reprogramming techniques will soon be available that don’t require genetic modification.) Next, the reprogrammed cells would be merged with an early stage embryo, created by sperm fusing with egg in a laboratory dish. The “chimeric” embryo would be cultured for a few days and then implanted into a woman. If a baby was born, he or she would contain cells from two genetic individuals: the embryo and the human who supplied the cells. The baby would have three parents: two who gave the gametes for the embryo, one who gave the cells from a biopsy. (Such an individual would not be a clone. However, it is feasible that the chimeric embryo could be manipulated such that the original embryo only forms placenta and the reprogrammed cells form the body. This has been accomplished with mixtures mouse embryonic stem cells and mouse embryos, but not with mixtures of reprogrammed mouse cells and mouse embryos. )

The results of some quick internet research suggests that using human iPS cells this way would not be allowed: In the UK, creating or using embryos outside the body requires a special license from the government, so I’d guess that permission would need to happen proactively. The US lacks legislation on reproductive cloning, though some individual states ban it. Australia distinguishes between research embryos (created through technical manipulation or by mixing genes from three or more people) and reproductive embryos (created through fusion of sperm and egg) and allows only reproductive embryos to used to create an embryo. A document dated to 2004 from Japan banned, among other things, the creation of chimeric human-human embryos for research.

Continue reading "Cloning by reprogramming?" »

Posted by Monya Baker on April 15, 2008
Categories: Cloning, Ethics, Reprogramming/Pluripotency | Permalink | Comments (2) | TrackBacks (0)

The former head of President Bush’s council on bioethics, now says there shouldn’t be a ban against cloning human embryos for research. Instead, there should be a five-year moratorium against the process. Writing in the Weekly Standard, Leon Kass decries the fact that the US Congress did not pass a law blocking all forms of human cloning, and then says that this stricter form of the law is unnecessary now that researchers can turn to alternate ways of reprogramming.

Instead, he argues for a law that would ban “all attempts to conceive a child save by the union of egg and sperm (both taken from adults).” That’s because the new reprogramming techniques mean that a skin cell could generate egg and sperm cells, whether taken from a man or a woman (or a boy or a girl, for that matter).

Embryos created for the purposes of research would not be outlawed, but instead banned for four or five years as researchers are given more funds to perfect the reprogramming techniques. He does not rebut, because he does not raise, the argument that stopping work the creation of embryos for research through somatic cell nuclear transfer will delay efforts to prefect reprogramming techniques.

Kass writes “Cloning for the purpose of biomedical research has lost its chief scientific raison d'être” (i.e. making a pluripotent cell line genetically matched to a patient.) That’s because it will probably be much easier to reprogram whole cells from adult biopsies than it will be to pull out an adult cell’s nucleus, plop it into a donated egg, grow that “reconstituted embryo” to a blastocyst and make embryonic stem cells.

Kass is probably right, but he fails to mention two caveats.

First, while many scientists are hopeful that so-called induced pluripotent stem cells will really behave like embryonic stem cells, they still aren’t sure. Possibly, a reprogrammed skin cell could be coaxed into a pancreas cell or a heart cell, transplanted, and then “remember” that it started out as a skin cell. Also, no one wants to use the current technique (using viruses to insert genes at random places in the cells’ chromosomes) to make cells that would actually get put into people. Those are serious problems, but most scientists think they can be overcome.

Second, and more important, many scientists think that to understand how reprogramming works with viruses, they have to understand how reprogramming works in an egg. Most people think that requires transferring adult nuclei into eggs or early embryos, and trying to figure out what happens.

Just a little quibble: Kass says that recent success by Stemagen in cloning a human blastocyst depended on the technique that Shoukhrat Mitalipov’s team in Oregon used to clone monkey blastocysts to make embryonic stem cells . Actually, Stemagen did not use this technique but credits its success not with a new technique but with a supply of high quality eggs.

Posted by Monya Baker on February 21, 2008
Categories: Cloning, Ethics, Policy, Reprogramming/Pluripotency | Permalink | Comments (0) | TrackBacks (0)

A California woman has asked a Korean company to clone her dead pet, according to an article in the Guardian .

The scientist leading the cloning team, Lee Byeong-chun, formerly worked with disgraced Korean scientist Woo-suk Hwang to clone the first dog. While Hwang’s work cloning human embryonic stem cells was found to be fraudulent, independent analysis found that the dog was indeed a clone.

Snuppy, the first cloned dog, was born in 2005 after over 1,000 cloned embryos were placed in 123 carrier females to produce two live pups, one of which died soon after birth.

In 2006, the team announced that 167 cloned embryos transferred to 12 carriers produced 3 live pups, all of which were delivered by Caesarian section. The nuclear DNA came from the same female Afghan hound. The accomplishment used eggs collected from 23 female dogs.

Earlier this year, the same team reported that it had cloned a 14-year-old toy poodle from an aged toy poodle, but using egg donors and surrogate mothers from larger dogs. Three-hundred fifty eight “activated couplets” were implanted into 20 recipient dogs; 2 got pregnant, and one pup was born via Caesarean section. (Activated couplets are apparently enucleated eggs fused with donor cells and then stimulated to divide.) Previously, the team had cloned wolves.

The woman who ordered the clone apparently preserved the tissue herself after her pet had died. A company spokeswoman estimated the likelihood of success as around 25%.

Simply getting to a live birth may not mean a happy animal. Mouse clones often have respiratory problems when born alive. The first cloned guar died shortly after its birth because of respiratory problems.

Company executives told Reuters that the company could clone 30 pets a year, and the Korean Customs Service is looking into cloning drug-sniffing dogs.

A California company set up to clone cats shut down in 2006. The company had previously financed the work that led to the first cloned cat, which was published in 2002.

Posted by Monya Baker on February 19, 2008
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The regulatory body that approves all research on human eggs has just been given the green light for the production of chimeras.
Here is the article from the AP. The idea is that, with human eggs in short supply, researchers should be allowed to practice techniques on more readily available animal eggs. Also, several researchers believe the process can answer questions about how and to what extent an egg resets a nucleus from an adult cell into an embryonic state.

Ian Wilmut (who cloned Dolly the Sheep) put for the scientific rationale for chimeras last year. It’s called Man or beast? Man and beast!

Nature Reports has several related articles.

A summary of the UK Academy of Medical Science’s position paper on human-animal chimeras

In a research highlight, the scientist who cloned frogs has studied how nuclei in cloned embryos remember the differentiated cells they came from.

Following the finding that, at least in mice, fertilized eggs could be used for cloning, we looked at the implications for humans and at the power of the egg to reprogram.

Also, an article on successful monkey cloning showed the necessity of good technique.

And recent news coverage describes advances in cloning human embryos from adult cells.

Posted by Monya Baker on January 18, 2008
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I asked veteran Nature reporter David Cyranoski what he had to leave out of his recent article that might interest Nature Reports Stem Cells Readers. Here's what he had to say:

They didnt use the OOsight imaging system that the Oregonians thought so crucial. (See Nature and NRSC stories on cloning monkey stem cells) They DID use
Hoechst, but they tried to minimize the UV exposure by using a very narrow
beam focused on just where they expected teh spindle to be. They did not
expose the whole cell. So, they did try to limit damage that Mitalipov was
worried about. Also, they didnt take too much cytopolasm or time.

If the first polar body wasn't in the near vicinity fo the spindle, they left
it in there. He [interview at Stemagen] said that there is no concern of the first polar body
creating a parthenote unless it is injected (ie, it cant merely fuse). He
focused on getting the whole thing over with very quickly. There seems to be
a trade-off between trying to treat the cell nicely (by not using Hoechst,
eg) and trying to do it quickly (use Hoechst, but get in and out).

Posted by Monya Baker on January 17, 2008
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An article at News at Nature today describes an advance in making human embryonic stem cells through nuclear transfer, or therapeutic cloning. Also, this month, a separate article describes making human embryonic stem cells by taking cells from embryos without destroying them.

The cloning group at California company Stemagen credits their success not with the technique reported for the successful derivation of cloned monkey stem cells but with a supply of oocytes freshly collected from women donors.

The group did not make a cell line but rather generated the early stage “hollow ball” embryos from which stem cell lines are normally produced. The group said they did not try to make a cell line because they didn’t have as many blastocysts as are normally needed to successfully make a cell line. Instead, they sent the blastocysts off for analysis to show that the cloning process worked. Robert Lanza, an unaffiliated researcher at Advanced Cell Technology (ACT) says that the blastocysts didn’t look very healthy.

The Stemagen accopmplishment is similar to what has been done before with two improvements: first that the cloned blastocysts were made using cells derived from adult cells. An earlier group had also gotten cloned human embryos to this stage, but without using adult cells. Another group at ACT that cloned human embryos could not make them grow past the six-cell stage.

Earlier this month, researchers at Advanced Cell Technology published results they had made several stem cell lines from embryos without destroying them. ( This follows on an announcement that Nature Reports first reported in June. ) The peer-reviewed article in Cell Stem Cell describes the production of five lines from individual cells taken from very early embryos without destroying them.
Conventional techniques pulls cells from the inside of the “hollow ball” stage of the embryo and destroy it in the process. This plucks one cell from the earlier “solid ball” stage when the embryo has around eight cells. The process is similar to that used in preimplantation genetic diagnosis. The team used frozen one-cell embryos that they cultured to the 8-cell stage. After the biopsy, the cells remaining in the embryo were allowed to continue growing.

In one set of experiments, one of the 26 embryos yielded a cell line, and 22 of 26 biopsied embryos continued development. A second set of experiments yielded a much higher efficiency, but a similar number of embryos that made it to the blastocyst stage after biopsy. A third set tweaks culture conditions and shows that biopsy-desrived embryonic stem cells don’t need to be cocultured with human embryonic stem cells. I saw no mention of how many frozen embryos would be expected to make it to the blastocyst stage without biopsy.

Posted by Monya Baker on January 17, 2008
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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
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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
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Today, the Human Fertilisation and Embryology Authority (HFEA) in the UK said that scientists could combine human chromosomes with animal eggs and try to make embryonic stem cells. It’s easier to collect unfertilized eggs from, say, cows than it is to collect them from women.

Interested scientists will learn in November if they’ll be licensed to make the attempts, which must be carried out under certain guidelines, but an article this month in Nature Cell Biology reminds us that even if the government says `yes’, some laws of science might say ‘no’.

In chimera-embryos (properly called `cybrid-embryos’ in this context), the chromosomes will be human, but at least some of the mitochondria will not.

Continue reading "Britain gives go-ahead on chimeras. Will science now block the way?" »

Posted by Monya Baker on September 06, 2007
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By Natalie DeWitt and Monya Baker

Monkey embryonic stem cells have, for the first time, been created through somatic cell nuclear transfer (SCNT). All attempts to make human embryonic stem cells through nuclear transfer so far have failed, but Jamie Thomson got the recipe for human embryonic stem cells by first doing so in monkeys, so researchers will likely be going to Shoukhrat Mitalipov of Oregon National Primate Research Center for advice. Mitalipov made his announcement Monday at the International Society for Stem Cell Research in Cairns, Australia, in a special add-on presentation . This finding represents a proof of principle that therapeutic cloning to create patient-specific ES cell lines could work in primates.

Continue reading "Oregon scientist reports first ES cells from cloned primate embryos" »

Posted by Natalie DeWitt on June 18, 2007
Categories: Cloning, Regenerative medicine, Reprogramming/Pluripotency | Permalink | Comments (0) | TrackBacks (0)

Posted by Natalie DeWitt for Monya Baker

South Korean scientist Woo Suk Hwang actually did achieve an important first, just not the one he claimed. I was at the meeting where Hwang said, falsely, that he’d created the first human embryonic stem cell through cloning. It felt like a rock concert, except attendees held up recorders instead of lighters.

It turns out that Hwang might have gotten some rock-star status just by sticking to the truth. The human embryonic stem cells he made came from a parthenote, or an activated, unfertilized egg, and he really did do it first. George Daley, a stem cell scientist from Children’s Hospital, Boston, announced this fact to an absolutely packed crowd in an exhibit hall at the International Society for Stem Cell Research in Cairns, Australia. That Hwang's line came from a parthenote had been suspected, but this line of evidence hadn't been presented before.

(Last year, Tiziana Brevini and Fulvio Gandolfi of the University of Milan announced that they had derived two stem cell lines from 104 eggs that had been donated to fertility clinics. The news story is here: http://www.nature.com/nature/journal/v441/n7097/full/4411038a.html)

Over a year and a half ago, everyone assumed that cloning human embryonic stem cells had been reduced to practice. Now, Hwang is a symbol for the biggest scientific fraud so far this century.

Daley described how embryonic stem cells derived from parthenotes could generate transplant tissue less subject to immune rejection, and I think about how when I bump in from stem cell scientists from South Korea, they tend to bring up Hwang in the first few sentences. They have done nothing wrong, but they still seem embarrassed. Had Hwang simply stuck to his real achievement, they would be proud.

(In a subsequent post, I’ll describe Daley’s work comparing how embryonic stem cells made through cloning differ from their parthenote-derived equivalents.)

Posted by Natalie DeWitt on June 18, 2007
Categories: Cloning, Regenerative medicine, Reprogramming/Pluripotency | Permalink | Comments (0) | TrackBacks (1)

In the aftermath of the Hwang scandal in 2006, Nature editors thought long and hard about whether journals could employ editorial procedures that might prevent publication of such fraudulent data in the future, at least in the area of cloning and nuclear transfer research. We queried several top scientists in the cloning and stem cell fields on this issue, and published the major conclusions in the editorial entitled Standards for papers on cloning.

Several of these scientists have agreed for Nature Reports Stem Cells to publish abridged versions of their 2006 answers in The Niche. Open the Comments below to read the postings of George Daley, Shin-Ichi Nishikawa, Alan Trounson, Alan Colman, Robert Lanza, Teruhiko Wakayama, Bob Wall, and Mark Westhusin, on whether the Hwang scandal could have been prevented, and what tactics journals should implement in the future to tighten up cloning papers. Feel free to join in the discussion by posting your own comments.

Continue reading "How can journals improve peer review of cloning papers?" »

Posted by Natalie DeWitt on June 05, 2007
Categories: Cloning | Permalink | Comments (10) | TrackBacks (2)