!Safe! Induced Pluripotent Stem Cells

Robert Lanza is now reporting that his research group has produced induced Pluripotent Stem Cells (iPS) that are safe for use in humans. The website, Red Orbit, has provided a link to the original (.pdf)article. See the Time magazine news article, here.

Lanza gives credit to the pioneering work of Shinya Yamanaka:

Dr. Robert Lanza, chief scientific officer at Advanced Cell Technology (ACT), reported today in the journal Cell that his team has created stem cells using human skin cells and four proteins. The innovation builds on the breakthrough discovery in 2006 by Shinya Yamanaka, who similarly coaxed human skin cells to revert to a pristine, embryonic state by introducing four key genes into the cells, piggybacked on viruses.

The technique relies on proteins that induce reprogramming of the cells, rather than genes or viruses. These appear to function in a manner analogous to the stimulating factors that are currently the standard of care for low blood cell counts: The body - in this case, the cell - begins to function the way it's wanted when certain proteins are introduced.

In this study, patients' own skin cells were harvested by a small biopsy. Approximately one in 10,000 of those cells were induced to revert to the embryonic stage. While this 0.001% seems a minute fraction, it's much more significant and achieveable than the production of patient-specific cells from cloned embryos, where each cell line would require multiple donor oocytes - "eggs" - harvested from women. Obtaining those oocytes has not proven very easy, even without the ethical problem of creating and destroying a human embryo that is the twin of the cell nucleus donor.

Fasten your seat belts - things will move fast, now.

Study of iPS cells draws nearer to finding cures

Research in stem cells and the origin and treatment of disease is definitely moving away from destructive embryonic stem cell research toward induced pluripotent stem cells (iPS).

A fantastic review that connects Japan's Dr. Yamanaka, San Francisco's Srivastava, the University of Texas Southwestern Medical Center in Dallas, and the Burnetts of Sulphur Springs, Texas, is published in the Japan Times. (Written by Rob Waters for Bloomberg news.)

Yamanaka, a professor at Kyoto University, developed a technology that may make the argument moot. Yamanaka, who has two daughters, started his effort 10 years ago, after peering at a tiny embryo through a microscope and reflecting that it might form a child if it wasn't used to make stem cells, he said in an interview.

"That's the moment I thought about this project," he said. "I saw that if we could make pluripotent stem cells without using human embryos, that would be ideal."

In 2006, he scored his first success. Using a virus to insert four genes into the skin cells of mice, he started a process that returned the cells to a primordial state able to form any other cell in the body. Yamanaka named them induced pluripotent stem, or iPS, cells. The next year, he repeated the feat with human cells.

Yamanaka and researchers elsewhere are now racing to find better ways to achieve the same effect. They would like to get rid of the virus, which can cause the genes to lodge permanently in the structure of the cell and may trigger the growth of tumors.

Yamanaka's technique exploits a basic fact of human biology — that every cell in a person contains the genetic instructions that set that person's traits, from hair color to inherited disease. By taking skin cells from a person with a disease and turning them into cells in the heart, brain or pancreas that are affected by a genetic disease, researchers can experiment with disorders at their earliest stages, Harvard's Melton said.

Labs are now creating iPS cells because making them is far simpler than getting cells from embryos, said Jeanne Loring, founding director of the Center for Regenerative Medicine, part of the Scripps Research Institute in La Jolla, Calif.

"Every stem-cell researcher I know has made about a dozen," Loring said.

She estimates that researchers have made 300 different so-called lines of iPS cells, a number that may double this year. Each line is a colony of cells descended from the first ones made. Scientists keep them alive in culture and the cells keep replicating.

Grants of $23 million awarded last June by the California Institute for Regenerative Medicine, the state's stem-cell funding agency, show that researchers are embracing iPS cells. Of 16 grants awarded, eight went to teams developing new iPS cells and five to groups comparing iPS and embryonic cell types. Just three went to scientists proposing to work solely with embryonic cells, according to the San Francisco-based agency.(Emphasis mine.)

And actual treatments are coming soon:

In 2004, Srivastava, then working at the University of Texas Southwestern Medical Center in Dallas, went with colleagues to Sulphur Springs, Texas, to collect blood samples and perform ultrasound scans on members of the Burnett family.

The researchers analyzed the genes of family members and found that 11 had heart-valve defects linked to mutations in a gene called Notch1, which plays a role in the formation of many organs, including the heart.

People with this mutation make half as much of the Notch1 protein as they should and their heart valves develop abnormally. The protein shortage primes their valves to take on extra calcium, which, over time, makes them stiffen, malfunction and require replacement.

Four years after his Notch1 discovery, Srivastava, now the director of the J. David Gladstone Institute of Cardiovascular Disease, supervised as the Burnetts had a pencil-shaped skin punch pushed into their calves to extract a bit of skin. When the boy's turn came, his 12-year-old brother, Ryan, laid a comforting hand on his back.

The iPS cells made from the Burnett's skin will be coaxed to become heart cells that carry the Notch1 mutation, Srivastava said. He plans to use the cells to test for drugs that boost levels of the Notch1 protein. This, he reasons, should make the hearts of people like the Burnetts more resistant to the entry of calcium and reduce the mineral's buildup on the valves.

A drug that could do this may essentially prevent the disease, Srivastava said. That is because the condition is present at birth, yet symptoms usually take decades to develop, giving a medicine ample time to work.

Within five years, Srivastava predicts, he will have found the right drug and be ready to start human clinical tests. A closely held company named iZumi Bio Inc., in California, will collaborate with Srivastava on this and other research involving iPS cells, Seidenberg of Kleiner Perkins said.

Texas Legislators Seek to Limit Funds for Human Embryo Destruction

Senator Steve Ogden is a Texas Hero!

Sen. Steve Ogden, R-Bryan, though, said critics exaggerate what his 24-word "budget rider" would do. He said it simply assures that the budget's $700 million for research doesn't underwrite destruction of embryos.

"There is a significant moral concern amongst many Texans that a human embryo really meets every scientific definition of human life that's out there and that we shouldn't be using human embryos for scientific experiments," Ogden said.

The dispute flared early last week. The Senate Finance Committee, which Ogden heads, took only two minutes late Monday to consider his rider. It says, "No funds appropriated under this act shall be used in conjunction with or to support research which involves the destruction of a human embryo."

The provision was adopted, 6-5, with Sen. Robert Duncan, R-Lubbock, joining four Democrats against.

The Dallas Morning News reports (free registration required) that some Texas embryonic research advocates claim this move will "embarrass" Texas. Of course, they also claim that embryonic stem cell research only involves "embryos that would be discarded, any way" Since we know that much of the research involves specially created, "disease specific" embryos, the latter is false.

And so is the first objection. Every week, we are reading about new ways to reprogram adult cells to achieve the stem cells that are needed to study and treat disease without ever going near an embryo. Former proponents of embryonic research and producers of new embryos for stem cell research like George Daley are switching their focus toward non-embryonic research. Texas researchers have been early stars in this research, among the first to using umbilical cord blood for stem cell research.

Texas doesn't need to waste our money following the false trail of embryonic stem cell research when there is so much promise in more treatments, sooner, from non-destructive and non-embryonic research.

Obama will fund more losing embryonic stem cell research (New Yellow Brick Award to the President)

Just days after we hear about functioning induced Pluripotent stem cells from adult skin cells, cells that can produce dopamine, the proteins missing in Parkinson's disease, we read that President Obama is going to overturn the limits on funding for embryonic stem cell research. Despite the fact that these cells match the patient because they come from the patient, that they will be cheaper, more accessible and we believe have less risk of causing cancer, this Monday morning, the 9th of March, 2009, the White House plans a quiet ceremony to sign the Executive Order.

Follow the Yellow Brick Road, Mr. President. The great embryonic Oz will get you home. Do not look behind the curtain, ignore that little man.

"Stroke of the pen, law of the land. Kinda cool!" (Thank you, Paul Begala.) We've been trying to spend a Trillion dollars every 10 days in the Obama administration. Let's just throw more good money after bad.

Typical of the news articles, is this one, from the US News and World Report, entitled (sigh)"Obama to End Stem Cell Ban Monday
Researchers applaud his action, which is expected to kick-start efforts to unlock therapeutic potential."

I recommend that you read that link above, in order to compare reality with what the proponents of destructive embryonic stem cell research believe.

The article is so full of holes. The title and first paragraph say "ban." There never was a ban. Ask Daley and Melton of Harvard who have been creating embryos for destruction to harvest the parts.

And then, there's this gem of an emotional non sequitor, I'm afraid from my State of Texas:

"It's going to remove an embarrassment for American science," said Dr. Darwin Prockop, director of the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White Hospital in Temple, said in February. "It's a statement that we're going to again believe in science."

Prockup must have been teased too much about his name as a child. Seriously, who among us stopped and now started to believe in science again?

We are not behind, we are not embarrassed, unless it's in imposing regulations. Even the "Progressives" are calling for more restrictions. The UK has more regulations on regenerative medicine and embryonic research than the US. France, Germany and Israel have similar limits on funding. Germany, at one time had criminal charges and fines attached to their ban.

CIRM has $3 Billion which must be spent on cloning and embryonic stem cell research. Their "Strategic Plan?" (This is a pdf, for a review, read this article at the CIRM website.) One cure and 2 trials in ten years. Who thinks the US is going to top their billions in embryonic research, when results with induced Stem Cells are bounding ahead?

Oh, I know, CIRM thinks the NIH should buy their $400 Million in bonds, this year. No one else wants the losing proposition.

Non-embryonic stem cells to cure Parkinson's?

The journal, Cell, has published an article (free abstract, full article and supplements for purchase) on patient-derived induced Pleuripotent Stem Cells (iPSC's) that appear to be brain neurons that produce dopamine, which is lacking in Parkinson's patients.

Besides being derived from the patient's own skin cells (they won't be rejected and are cheaper and more accessible to more of us than embryonic), and being non-destructive (no embryos destroyed - and, did I say, cheaper and more accessible?), these iPSC's were derived using viruses that can be purposefully, and apparently, fully removed from the culture.

The plans apparently are to use the cells to study the disease. However, with the history of the debate over this disease, I wouldn't be surprised to see them used to treat the donors' Parkinson's disease very soon. Parkinson's is so devastating to patients and their families that several attempts to use brain transplants of aborted embryonic and fetal tissues have been used on real patients, with disastrous results. These iPSC's should be safer than fetal tissues.

AMA: "People aren't going to waste time on Embryonic Stem Cells, anymore"

A member of the "lobby group Comment on Reproductive Ethics" maintains that there are "some scientists who like to hold on to what they've got, but" she doesn't "think people are going to waste time on embryonic stem cells any more."

(Josephine Quintanelle, quoted in the Guardian, 3/1/09)

The American Medical Association sends its members a "Morning Rounds" email with the latest headlines on science and medicine. The articles have more links than my posts and the editors seem to choose that days' big story.

Today's big story is that the Washington Post (free registration required) reports on a from a Letter to the journal, Nature. Two groups of scientists, one from Toronto (Andras Nagy, from the University of Toronto) and another from Edinburgh (Dr Keisuke Kaji, at the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh) have found a way to make skin cells transform into embryonic-like stem cells without using viruses.

This should lead to a cheaper way for people to have their own cells transformed into therapies. Farther down the line, it could help us treat disease and injury -and aging - in place, by inducing repair where it's needed and without transplants. On the other hand, if we use embryonic stem cells, it would be necessary to make a clone of each person or find some sort of universal donor cell that would not be rejected. The previous way of reprogramming cells to an embryonic stage used viruses that could not be removed and which have the potential to cause cancer if left in the DNA of the cells.

The scientists used human fibroblasts - a type of skin cell - which were treated with a "jumping gene" from a cabbage looper moth, that inserts itself into chromosomes along with the genes that "reprogram" the fibroblast -- then, the extra gene can be removed.

From the Post, a very clear description.

The alternative cells, known as induced pluripotent stem cells, or iPS cells, appear to have many of the same characteristics as embryonic stem cells but are produced by activating genes in adult cells to "reprogram" them into a more primitive state, bypassing the moral, political and ethical issues surrounding embryonic cells. Until now, however, their use has been limited because the genetic manipulation required the use of viruses, raising concerns the cells could cause cancer if placed in a patient. That has triggered a race to develop alternative approaches.

"These viral insertions are quite dangerous," Nagy said.

In the new work, Nagy and his colleagues in Toronto and at the University of Edinburgh in Scotland instead used a sequence of DNA known as a transposon, which can insert itself into the genetic machinery of a cell. In this case, the researchers used a transposon called "piggyBac" to carry four genes that can transform mouse and human embryonic skin cells into iPS cells. After the conversion took place, the moth gene, called "piggybac" lost its ability to insert itself into the chromosomes of the cells and "disappear" or can be removed.

"PiggyBac carries the four genes into the cells and reprograms the cells into stem cells. After they have reprogrammed the cells, they are no longer required, and in fact they are dangerous," Nagy said. "After they do their job they can be removed seamlessly, with no trace left behind. The ability for seamless removal opens up a huge possibility."

Unfortunately, for some reason the scientists used (non-stem) fibroblast cells from embyros as the cells that are reprogrammed, so the research is being repeated in cells from non-embryonic sources.

Other news articles on the breakthrough are at BBC News, Nature News,
AFP, Financial Times, the Candian Press, the Guardian and the Globe and Mail.

Human cloned embryos

Oddly, there is very little notice of the confirmation that Advance Cell Technology has created cloned human embryos. Current bioethics and science reporting evidently takes the creation and destruction of human embryos for granted. In fact, the embryonic humans were created with the intention of destroying them.

No one - or almost no one - seems to notice.


Wired Science has one of the few reports that narrows in on what should be the headline:"Research Breakthrough: Human Clones May Be Genetically Viable."

It is significant that (as reported earlier) human-animal hybrid embryos do not appear to be a practical source for human embryonic stem cells. However, after reading the article itself, it appears that the story with in the story may be - I believe should be - even more significant.

The article, "Reprogramming of Human Somatic Cells Using Human and Animal Oocytes," is available online and free, here, in pdf form. Supplemental information is available here.

Lanza and his colleagues report that they used human eggs and human donor DNA to create about 50 cloned human embryos, all females. They also write that they used a human embryo started by in vitro fertilization as a "control," or material to test the validity of their other results.

Cells were removed for testing from some of the cloned human embryos and the IVF human embryo. Other than that, we do not know the fate of these embryonic human girls.

Edited January 27, 2010 to correct a "Label" typo

Human-animal embryos don't work for stem cell production

The New Scientist has a good review article that explains a new research report from Robert Lanza of Advanced Cell Technology, that attempts with "thousands" of embryos created by placing human DNA into the oocytes or eggs of animals have failed to produce stem cells. NatureNews, the news arm of the journal, Nature discusses the report, here.

The abstract of the article, "Reprogramming of Human Somatic Cells Using Human and Animal Oocytes" published in Cloning and Stem Cells, is available here. The list of researchers is very long and they are from several different laboratories.

Each of the news articles above includes statements from researchers who do not believe that human-animal cloned embryos are a dead-end for stem cell researchers. However, the confirmation of the outcome from several labs, with different researchers, is strong evidence that it is unlikely that this technique is a reasonable way to produce "patient specific" stem cells - those that are an exact match for the donor of the DNA.

I have not read the actual article, yet, but from the news articles and the abstract, it appears that the "cybrids" do express the genes of the donor DNA and are clones of the donor. However, while enucleated human oocytes are able to reprogram the DNA of the donor to result in embryos that divide to the stage at which it is possible to harvest embryonic stem cells, the emptied eggs of cows and rabbits do not. The cybrids only divide to about the 16 cell stage and do not turn on the genes responsible for pleuripotency, or "stem-cell-ness."

See my Update, written after I read the report.

Fox builds hen house

In the same set of news alerts that notified me of the Vatican's condemnation of cloning and embryonic stem cell research, I read that Insoo Hyun is the lead author of the International Society for Stem Cell Research (ISSCR) Guidelines for the Clinical Translation of Stem Cells.

The Guidelines are also published on line at Cell Stem Cell and, along with a patient handbook and other supporting material, is available at the ISSCR website. Here is the link to the page containing links to pdf of the Guidelines, patient handbook, and other materials. That page also links to the Stem Cell Cell article.

The story in the Australian blurs the differences between destructive embryonic stem cell research and the non-destructive, ethical forms such as induced pluripotent stem cell research and adult stem cell research. The focus is on the former, detailing long anticipated (but not yet begun) phase 1 embryonic stem cell research, without mentioning on-going trials or previous achievements using the non-controversial cells.

The ISSCR in general and Dr. Hyun in particular, are very much advocates of embryonic stem cell research and cloning for research. Also on his task force were Laurie Zoloth and George Daley, both strong advocates of embryonic stem cell research. Daley has worked to create embryos slated for destruction in his own Harvard lab, although he has focused on non-destructive research, recently.

Dr. Hyun has a Ph.D. in bioethics and is on the faculty at Case Western University in Cleveland, Ohio. He has focused on cloning research, and his early work included assisting the Clinton Administration's National Bioethics Advisory Committee (that would have been along with Obama transition team members, Jonathan Moreno and Robin Alta Charo) on their "secular" article on cloning. He went to South Korea with Hu Suk Wu in order to study the effects of cloning research on the Koreans - before the Korean was exposed as a fraud.

I wonder whether there was even one member of the ISSCR team who considers embryonic stem cell destruction unethical? And how soon will Dr. Hyun join his former colleagues in DC?

Seed Magazine's Ethics and stem cells blog focus

Seed Magazine runs a group of blogs on science, ethics, politics and opinion. Most of the bloggers are engaged in academic science.

There's a new blog sponsored by the site, What's New in Life Science Research?

The first subject of the blog is stem cells. I was surprised to read the narrow range of knowledge and assumptions in the posts, propagating the same old fallacies: only those frozen in vitro fertilization embryos will be used, embryonic stem cells show the most potential, Bush cut off funding for stem cells with his Executive Order of August 9, 2001.

No Patent on Human Embryonic Stem Cells: EU

A Thanksgiving present from the European Union!


The Enlarged Board of Appeal of the European Patent Office (EPO) did not take the day off. Early on November 27, the EPO announced that they would not allow the development of human embryonic stem cells to be patented as filed by WARF in 1996, since that technique depended on the destruction of human embryos.

For background on WARF, see this post on the patents, here.

The EPO has upheld its previous ruling from earlier this year:

The EPC does not allow patenting inventions whose commercial exploitation would be contrary to public order ("ordre public") or morality. Furthermore, the Convention prohibits patenting on uses of human embryos for industrial or commercial purposes.

Needless to say, Geron is not happy.

Trash from Reuters on Stem Cells

Just read the first two sentences of this article.

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) - Stem cells from tiny embryos can be used to restore lost hearing and vision in animals, researchers said Tuesday in what they believe is a first step toward helping people.

One team repaired hearing in guinea pigs using human bone marrow stem cells, while another grew functioning eyes in tadpoles using frog cells.

What a disgrace! The second sentence/paragraph tells us the sources of the stem cells: (mesenchymal) bone marrow stem cells, which are adult stem cells and frog cells. There are no embryos or embryonic stem cells used in either experiment.

Here is a much better article on the frog's eye cells from pleuripotent (not embryonic) stem cells, at Science Daily:

Under normal conditions, pluripotent frog cells form only skin tissue. The scientists were able, however, to convert the pluripotent cells to retinal cells by forcing them to express the eye field transcription factor (or EFTF) genes. The reprogrammed cells formed all seven classes of retinal cells normally found in the eyes, including the retinal ganglion cells, which have axons (optic nerves) that extend to the brain.

Furthermore, these new cells eventually formed into functioning eyes. When tested, tadpoles used their induced eyes to detect light and to engage in a vision‑based behavior. The scientists also found a population of self‑renewing cells in the periphery of the induced retinas, suggesting that EFTF‑induced cells also formed adult retinal stem cells.

Click here to let the Reuters editors know they need to fix this story.

The (manufactured) Stem Cell Debate at Dartmouth

I don't believe I've ever seen a report on a presentation that allowed half the space for "debate," after the fact.

The Stem Cell Debate at Dartmouth

Sunday, November 16, 2008

Father Tadeusz Pacholczyk, Ph.D. was recently invited to give a lecture entitled “Stem Cells and Cloning: Understanding the Scientific Issues and the Moral Objections” at Aquinas House, in observance of the Feast of St. Luke, the patron saint of medical professionals. Pacholczyk, or Father Tad as he encourages his audience members to call him, is the Director of Education for the National Catholic Bioethics Center. He arrived at this position after receiving degrees in philosophy, biochemistry, molecular cell biology, and chemistry, a Ph.D. in Neuroscience from Yale University, and years of research in molecular biology, bioethics, and dogmatic theology. In a free public lecture lasting more than two hours, Pacholczyk outlined both the scientific and ethical considerations of human embryonic stem cell research and to a lesser extent cloning, giving justifications for the Catholic Church’s positions on these technologies.

After giving an in depth layman’s version of the science involved in stem cell research and a history of both scientific milestones and relevant policy decisions, Pacholczyk corrected what he believed were some of the most pervasive myths about stem cell research. He believes that individuals and organizations within the media and others who engage in expensive advertising campaigns have deliberately misled the American people in an effort to reframe the debate over the use of human embryos for research.

**************
The Dartmouth Review understands that this is an issue on which reasonable moral people can disagree, and so Michael S. Gazzaniga ‘61, Ph.D., Director of the Sage Center for the Study of Mind at the University of California, Santa Barbara was asked to explain some of the ethical justifications. He indicated that, “The handling of human tissue has always commanded the respect of the biomedical community and always will.” However, Gazzaniga does not consider an embryo to be in possession of the same moral status as an adult human, while acknowledging that the issue has “deep meaning to millions of people.”

The Review has raised several ethics questions regarding the virtual debate they created by interviewing Dr. Gazzaniga after Dr. Pacholczyk's talk.

Will they seek out opposing views in the future or is it only Catholic priests who require such answers? Will they now give Dr. Pacholczyk an opportunity to respond?

In addition, Dr. Gazzaniga finds the determination as to when a human being becomes a human being fairly simplistic:

Asked the basic question underlying this debate and that about abortion, when a human embryo becomes a human being, Gazzaniga called it a “social decision, not unlike the kind a society makes about when to call someone legally blind.”

Does Dr. Gazzaniga's emphasis on contrasting "adult" human beings with embryonic human beings indicate that he finds differing moral values in the lives of infants, children, and "adults," does he extend these differences to the state of function of the brain, and can he justify these variations at least as well as we can our culture's definition of "legally blind?"

Charo: No "Presidential sleight of hand" on stem cells

"The Wicker-Dickey Amendment cannot be changed by Presidential sleight of hand or wave of pen."

R. Alta Charo, World Stem Cell Summit, Madison Wisconsin, September, 2008 See video, at time marker 11:18/01:01:29.

John Podesta, the founder of the Center for American Progress and the leader of the transitional team for the newly invented "Office of the President Elect,"
told Chris Matthews of Fox News Sunday (transcript here) that Barack Obama intends to do what he can to change the US policy on "stem cells" by the use of the Presidential Executive Order (EO).

In light of current law (the Dickey Amendment) and regulations that seem to require legislation such as that vetoed by President Bush last year, some may join me in wondering how much the new President will actually be able to accomplish by the use of EO's.

In fact, according to one of the original members of the CAP's Progressive Bioethics initiative, R. Alta Charo, a lawyer with quite a bit of experience in this sort of law, it won't be as easy as Mr. Podesta said. Ms. Charo made the statement above as a keynote speaker for the program at that World Stem Cell Summit that I mentioned in September.

Videos of much of the program can be found here.

While searching for information on the current laws on embryonic stem cells, I found this blog, "World Stem Cell Summit 2008," . Blogger Kate Willet summarized the proceedings in an unofficial capacity. From the parts I've watched, her impressions on the program and speakers as it happened are fairly accurate.

The real-time video of R. Alta Charo's talk is here, and the paraphrased report is here.

Induced Pluripotent stem cells without viruses

"The adenovirus will infect the cells but then will clear themselves from the cells. After a few cell divisions there are no traces of the virus in the cell," Hochedlinger said. "You can't tell the virus was ever there."

Science Magazine has published a report on induced Pluripotent (iPS) stem cells from liver cells (hepatacytes) that do not show any trace of the viruses initially used to cause the regression from adult cells to embryonic-like stem cells. The report, by Hochedlinger's group at Massachusetts Gener al Hospital and Harvard, is behind a pay-wall, but there is a review here at the Washington Post.

The simple explanation is that viruses are used to carry copies of genes that turn on proteins which cause the cells to divide and produce embryonic-like stem cells. Prior research used viruses that might become permanently inserted into the DNA of the cells. These viruses did not cause an infection in the culture because the viruses used were not good at causing themselves to be reproduced or inserting themselves into neighboring cells. However, because they inserted themselves into the DNA, there was a risk that the cells could become mutated or even cause tumors due to the abnormal DNA that resulted. In the case of Hochedlinger's cells, the adenovirus used does not insert into the DNA nearly as often, and when it does, the cell is able to repair the DNA in subsequent copies of the DNA as it reproduces the nucleus of the cell in order to divide to become two cells.

The cells are infected, they change because of the infection, but their granddaughters are able to get rid of the infection, while continuing to act like embryonic stem cells instead of grown up liver cells. The new "adeno-iPS" cells pass all the tests for "stemness."

Just think, no need for egg cells, no cloning, no destruction of embryos, and we're one step closer to healing within the body - to learning how to heal without transplant rejection or tumors due to the treatment. One day, we may be able to regenerate organs and tissues in place, as needed.

"iPS cells would have never been discovered without human embryonic stem cells"

In fact, Mr. Siegal, without the objection to cloning and embryonic stem cell research, iPS cells researchers might have taken a little longer to develop therapy that holds promise for regeneration and healing in the body, without transplants, intermediate cells and without costing the life of another human being.

Bernie Siegal, that lawyer who sued the Raelians for custody of their supposed cloned children and who lauded Hu Wu Suk for his own cloned children, is hosting one of his "World Stem Cell Summits" in Madison, Wisconsin next week. He is joined by Robin Alta Charo in promoting the Summit and reminding all of us that the push is not over for more clone-and-kill embryos and federal tax funded research depending on embryo creation and destruction. No matter how successful induced Pleuripotent Stem (iPS) cells are turning out to be.

Siegal founded the Genetics Policy Institute, with the help of the National Heritage Foundation Inc:

The GPI is funded by individuals, foundations, academic institutions and scientific societies, including the American Society For Cell Biology, the American Society for Biochemistry and Molecular Biology, the Michael J. Fox Foundation for Parkinson's Research and the Huffington Foundation, according to Siegel.

R. Alta Charo (for some reason, she drops the "Robin") is a lawyer/bioethicist ( "for Hire")will deliver a keynote address at the Summit. She lobbies against physicians with consciences and in favor of abortion, cloning and embryo stem cell research. She's especially fond of the latter two, because (as she says in this audio copy of her lecture at the American Society of Bioethics and Humanities convention in 2006)she believes they will support her Progressive politics and belief that the research will support her personal belief that there is no Creator, so humans aren't so special, after all.

For a brief review of the history of "ethics for sale," look at this set of my posts.)

The Stem Cell Debate Heats Up

Here's a great review about those new "induced pleuripotent stem cells" (iPS) we've been hearing about. iPS's are truly "patient specific stem cells" since they come from the patient himself or herself. The cells are manipulated in the lab, using viral particles and specific environments to make the able to become many different types of cells.

It would be very difficult, in my opinion, to make these cells become embryos, with all the structures that would allow them to function as individual organisms. From what I understand, the cells return to a state that allows them to become tissues with several different types of cells and cell groups, but they are never organized.

In my opinion (again), the induction process can't be more of a problem than the risk of immune rejection and the manipulations that embryos derived from In Vitro fertilization go through or the changes that are bound to be inherent with cloned cells derived through Somatic Cell Nuclear Transfer. On the other hand, volunteers and tissue samples for IPC experiments ought to be abundant.

And no one has to die for it.

Human-pig embryo approved in UK

The "cybrid" or hybrid human-animal embryos are created in the laboratory by Somatic Cell Nuclear Transplantation, using emptied eggs from animals and the nuclear and cellular DNA from humans.. We know that there are currently experiments on-going with the human embryos made using emptied cow eggs (more on the "ease" of making these embryos, here), and now the British have authorized the development of pig-human embryos.

The experimenters admit that the problem will be achieving embryos and embryonic stem cells that do not contain DNA left from the egg. Proving the purity and "human-ness" of the stem cells will be a complication that I do not believe they will be able to overcome, at least for transplantation into humans, except possibly in the case of severe, last-hope disease and trauma.

The ethical debates about xeno-transplants and treatments using living organs, cells and tissues from animals carry the risks of transmitting animal diseases that humans have no immunity for and the development of new strains of disease that cross species lines. Ethicists have predicted that at least the early patients will have to live their lives in isolation at the worst, and have life-long surveillance at the best. (more on the debate, here and here.)

However, the researchers will probably be able to develop other uses, such as the early warning chemical weapon detection systems that are being developed by our own military, using human embryonic stem cells.

Rather than humanitarian and medical hope, I believe that time will show us that the research is the result of pure greed, with each lab hoping to come up with a product that can be patented and sold. I'm disappointed that the courts and "ethics" bodies in the US and UK have allowed these patents of human organisms. The drive to "create" new human cells and artifacts using human DNA is the logical outcome.

Human-DNA-in-cow-egg embryo created in UK

Scientists in the UK report that they have created an embryo using the transfer of human nuclear DNA from an embryonic human cell into the oocyte of a cow that has had the nucleus removed. These embryos are the "hybrids" or "cybrids" that we've been discussing for the last few years.

From the Guardian:

Apparently these researchers have achieved some success - but by using the nucleus from a very early embryonic cell, which might be easier to reprogramme than an adult cell. At the moment it is impossible to assess the significance of this report until we know more details of what has been achieved ... the results have been repeated and, importantly, they have been reviewed by independent researchers in the usual way."

Josephine Quintavalle, of the pressure group Comment on Reproductive Ethics, said the research should not worry those opposed to hybrid embryos because the Newcastle work did not seem convincing. "The embryos didn't survive, they were created from embryonic stem cells rather than adult tissue, and there's a lot of question marks over the research."

But she added: "What it has done is wake up the public to this reality, that while parliament is getting in a tizz about this, while the whole country is up in arms discussing it, the HFEA is already issuing licences."

Supposedly, if the technique is perfected to allow the embryos to survive longer, these embryos will allow the study of the early embryo and production of embryonic stem cells in order to learn more about and find cures for diseases like diabetes and Parkinson's.

However, even if the embryos are disorganized and fail early, or if they are destroyed at day 5 or 6 or whenever, the ethical determination as to whether they are "human" or "bovine" has not been cleared up. We won't know what they are until several labs and several trials successfully create these embryos.

If the embryos appear to divide in an organized manner, producing human proteins and the differentiation necessary to create human embryonic stem cells, then they are essentially human embryos. This is a case of the old if it walks like a duck, quacks like a duck, etc., logic.

Since the stated intention is to destroy the embryo, and we don't know whether they are human or not, those of us who find the killing of humans, even at the earliest stages will also hold that it is inherently unethical to even begin the process.

A discussion about the discussions about the announcement can be read at one of Nature.com's blogs, "The Great Beyond."

From the thread, "UK hybrid embryo: in perspective - April 02, 2008,"

New Scientist has attacked the group for announcing the achievement through the media rather than through a scientific publication. The Independent focuses on the ethical debate. Not many organisations outside the UK gave it any coverage at all, and those that did may have been under the impression that it was a world first, not mentioning previous achievements in the field (eg. Life Scientist, Australia).

Nature Reviews Stem Cell Heart Treatments

The journal, Nature, has published a review article, "Stem-cell therapy for cardiac disease,"
about treatment of heart disease with stem cells, focusing on the many types of cells that are being used in research, including bone marrow derived stem cells and progenitors and "resident" cardiomyocyte stem cells. The latter are actually found in the heart and can be harvested from the patient who needs them and used to repair damaged heart disease.

The abstract promises more than I ever thought I'd read in a "First tier" journal.

Heart failure is the leading cause of death worldwide, and current therapies only delay progression of the disease. Laboratory experiments and recent clinical trials suggest that cell-based therapies can improve cardiac function, and the implications of this for cardiac regeneration are causing great excitement. Bone-marrow-derived progenitor cells and other progenitor cells can differentiate into vascular cell types, restoring blood flow. More recently, resident cardiac stem cells have been shown to differentiate into multiple cell types present in the heart, including cardiac muscle cells, indicating that the heart is not terminally differentiated. These new findings have stimulated optimism that the progression of heart failure can be prevented or even reversed with cell-based therapy.

New York Times article on cloned humans

The New York Times (free one time registration required) has a news piece on the Stemagen cloned human embryos, with reference to "making copies of people" and implantation of cloned embryos for reproduction.

One of the men who donated the fibroblast skin cells is also the owner of Stemagen.

The NYT has more on the story behind the cloned human embryos:

The Stemagen scientists, led by Andrew French, an animal cloner recruited from Australia, used skin cells from Dr. Wood and another Stemagen employee as the DNA source. They used 29 eggs donated by young women at the fertility clinic that Dr. Wood manages.

Five blastocysts were developed. One was shown to be a clone by genetic testing, the scientists reported, and two others also showed good evidence of being clones.

Dr. Wood said the key to success might have been choosing egg donors who were known to be fertile and healthy because they had previously been successful donors at his fertility clinic.

The women were also donating at the same time to couples wanting babies. Some eggs went to the couples and the others to the research, with the consent of both the donors and the couples. The donors were paid for the eggs that went to the in vitro fertilization but not to the research, Dr. Wood said.

Therapeutic cloning has been hampered by lack of access to healthy eggs, in part because it is often considered unethical to pay women for such donations. Dr. Daley of Harvard said Stemagen’s “egg sharing” approach appeared to be a reasonable way to obtain eggs.

The media will have fun with this story.

Human embryos cloned in California

Scientists at Stemgen, a La Jolla, California laboratory have published a report on the successful cloning of human embryos in the journal, Stem Cells. (The article is available free, due to the open access policy of the journal.)

The authors are very clear: these are human embryos produced by somatic cell nuclear transfer or cloning. The embryos were clones of the men who donated the fibroblast skin cells.

This study demonstrates, for the first time, that SCNT can be utilized to generate cloned human blastocysts using differentiated adult donor
nuclei remodeled and reprogrammed by human oocytes. Evidence of successful SCNT was shown with DNA fingerprinting analyses of three SCNT cloned blastocysts where embryo genomic DNA was that of the donor fibroblast cell line and were not fragmented oocytes or of parthenogenetic origin.

. . .DNA fingerprints from three SCNT blastocysts were consistent with those of the somatic cell donor employed with no evidence of contamination from the egg donors, indicating that embryonic development was being controlled by the donor cell genome.

The cloned human embryos were produced using donated oocytes less than 2 hours old and the DNA from the skin cells of men. (The eggs were donated by women for the use of other couples, see below.) The use of male donor DNA allows for easier distinction from any possible parthenogenetically produced embryos, which would be female. Any embryos that are male serve to prove the success of the experiment.

In this case, the cloned embryos were actually compared to parthenogenetically produced embryos created by stimulating oocytes to become embryos. These embryos only contain the DNA of the women who donated the eggs. Parthenotes are not clones, because of the rearrangement of genes that happens when the eggs are produced with half of the normal chromosomes which would be matched by the haploid sperm if fertilization took place.

It appears that the group had a very high success rate, with approximately 2/3 or 16 of 25 of the enucleated oocytes producing very early embryonic organisms, which (who) demonstrated cell development and division similar to embryos produced by in vitro fertilization. 10 of the embryos developed to day 3 and 5 of those went to day 5, with the formation of blastocysts. Blastocysts are embryos that have developed enough cells to form a layer of cells around a hollow center, and eventually the inner cell mass, the differentiated grouping of embryonic stem cells at one spot within the sphere. All 5 of the blastocysts formed inner cell masses. The authors do not report any stem cell lines from these embryonic stem cells, but note that they are trying to do so - either from these embryos or from additional cloning.

The Discussion includes speculation that the success rate was so high because the oocyte donors were young women who were able to produce so many eggs through stimulation of their ovaries that there were more than enough for the use by the parents (couples?) to whom they were donating for the production of embryos for implantation and pregnancy. Although the article states that all 3 of the parents were able to get pregnant from the eggs that went to them, that could not have been known at the time the eggs were taken to the experimental lab. Some went to the in vitro lab and some went to the experimenters within less than 2 hours. It takes at least a few hours after in vitro fertilization to determine whether any embryos were formed.

If embryonic stem cell lines are developed from this technique, perhaps some group will compare them to embryonic-like stem cells developed by reprogramming.

Myths on Myths about stem cells

There's a new Public Broadcasting System (your tax dollars at work) television show on "stem cells," "Mapping Stem Cell Research: Terra Incognita."

You don't have to go any farther than the top of the home page, with its picture of a girl in a wheelchair and this quote,

"Some people consider stem cell biology to be the Holy Grail of Regenerative Medicine, while others view embryonic stem cell use as morally wrong."

to see that it's propaganda for embryonic stem cell research and cloning for embryonic stem cells. The authors immediately begin the pattern of using the term "stem cells" for both of the two basic kinds of stem cells: those that require the destruction of a human life and those that don't.

Here are the first three points from the "Myths and Realities" page, with my comments in Bold after each.

MYTH
Stem cell research uses aborted fetuses.
REALITY
Stem cells can be totipotent (a fertilized egg with the “total potential” to give rise to all different types of cells in the body), multipotent (stem cells that can give rise to a small number of different cell types), or pluripotent (stem cells that can give rise to any type of cells in the body except those that are needed to develop a fetus). While pluripotent stem cells could be developed from fetal tissue or even adults, they are best derived from early-stage embryos, a mass of cells that is only a few days old—not aborted fetuses.

The authors skip over the significance of the fact that embryronic stem cells come from destroyed human embryos in the lab, it is true that most stem cell research does not use tissues obtained from abortions. Nowadays, however, the term "fetus" is too often used by the media (and even researchers who ought to know better) for all pre-born human beings. The proper definition of human embryo is the organism from fertilization or the beginning of the first cell division to 7-8 weeks of age. The term "fetus" in humans is properly used from 8 weeks until birth.

More on the claims about what is the "best" source of stem cells and about "embryonic-like stem cells," below.

MYTH
Somatic cell nuclear transfer using human cells involves the use of fertilized eggs.
REALITY
Somatic cell nuclear transfer, the process in which the nucleus from an adult cell is removed and then transferred to an egg whose nucleus has been removed, is the first step in cloning and can be used to create an embryonic stem cell line. However, an egg cell does not need to be fertilized to be used in this procedure—an unfertilized egg cell can be used.

Here, the authors avoid using "embryo" and throw around the terms "unfertilized egg" and "fertilized egg." An embryo is not a "fertilized egg" - once an egg is fertilized, it becomes an embryo. In Somatic Cell Nuclear Transfer (cloning), the embryo is produced artificially by inserting the DNA of a donor cell and stimulating division and organized development that occurs with natural reproduction. When human DNA is used to produce human embryonic cells in an organized embryo, there can be no doubt that what we are talking about is a human embryo. No matter how he or she is created - or produced - or how severely handicapped by the intentions and actions of the producers, a human embryo is a very young human being.

MYTH
Researchers can use adult stem cells instead of embryonic stem cells. Other treatments using adult stem cells are available to treat conditions such as Parkinson's disease and spinal cord injuries.
REALITY
Adult stem cells lack the versatility and flexibility of embryonic stem cells, making them less likely to lead to medical breakthroughs. Embryonic stem cells have a far greater developmental potential and are more likely to be pluripotent, while adult stem cells are thought to be merely multipotent, or restricted to only certain cell types.

In November 2007, Japanese and American research teams reported new ways to obtain stem cells that behaved like embryonic stem cells from human skin cells—without having to use human embryos. This breakthrough holds great promise in solving the ethical dilemmas of stem cell research, but scientists currently still face technical hurdles and the challenge of finding ways to use these stem cells successfully in medical treatments and therapies.

The biggest lie of all is that embryonic stem cells are more useful in treatments for human beings. Just ask the 20,000 plus in the US alone who have been treated with adult and umbilical cord stem cells or go looking for even one human who has been treated with embryonic stem cells.

While it is true that most ethical, adult stem cells are not "pluripotent," there are many kinds of "multipotent" stem cells and precursor cells in the body. In fact, these are the cells that we probably will use in the future, because they are the cells the body uses to repair itself and because they are less likely to grow out of control or cause tumors.

We are also learning that the desired development of stem cells and precursor cells is influenced by the environment and all sorts of "factors," or chemical and physical signals present in the part of the body where they grow into cells, tissues and organs. The key to future treatment for most disease will probably come from learning to stimulate these conditions and factors.

Besides the ethical dilemma of destroying early human life, embryonic stem cell research has every problem or hurdle that could be cited for adult stem cells: they are difficult to grow, found in small numbers, the cultures may be contaminated with different, undesirable cell lines, and are difficult to control to produce for the exact stem cell line that is needed.

Moreover, no one wants to transplant embryonic stem cells into people. What we want is to produce adult stem cells for treatments.

The last paragraph mentions embryonic-like stem cells. There are several ways to produce stem cells that behave in every way that the unethical stem cells do.

These cells are being used in research to replace the unethical cells produced by destruction of embryos.

The goal of all stem cell research is to have a source of "patient-specific" stem cells from the patient or to find ways to stimulate stem cell production in the body of the patient, when and where they are needed.

The producers of this program are advocating for outdated research methods.While researchers have learned a lot from human embryo research in the past, most of what we use has been developed from research in animal models. The production of new embryonic stem cell lines from human embryos and from cloning is no longer necessary to carry out this research.


(Thanks to Janet, of the Bedford County Citizens Concerned for Human Life, for sending me the link to the website on the show.)

Lee Silver: iPCs named due to politics

Lee Silver, author of is someone that I've read about on the 'net and about whom Robert George and Patrick Lee said, "He hides his ideology under a veneer of science."


He was the guest on Carl Zimmerman's Bloggingheads.tv November 30, discussing reprogrammed skin cells.

Dr. Lee is convinced that if a couple of more labs reproduce the reprogramming (and others have since, Jaenisch and Yamanaka's lab have already published follow-up results), then reprogramming will probably be the way we get embryonic stem cells, rather than by destruction of embryos.

However, he claims that the naming of the cells "induced Pluripotent Stem cells" or iPC's is a political move to hide either the fact that the opponents of embryo-destructive research are being fooled or being hypocrites.

From the thread following the interview:

Actually, human ES cells (unlike mouse ES cells) are perfectly capable of differentiating into trophoblast (Nature Biotech 20:1261; 2002). Why do you think this isn't common knowledge? (Hint: politics) And mouse ES cells can be turned into whole mice quite efficiently with a technique that does NOT involve blastocyst injection or tetraploid embryos (Nature Biotech 25:91; 2007). Concerning your next post, how do you know what the intent was behind naming these cells iPS cells?

. . .

The question is whether continued research will soon get us to the point where fibroblasts cells can be transformed into cells that are completely indistinguishable from human ES cells, with the potential to form every human cell type (including, eventually, blastomeres which could, in theory, develop into babies without any further "tinkering"). With all of the accomplishments of the last ten years, it is very hard to imagine that this won't be possible. The ONLY reason to doubt it is based on a religious-inspired faith that there is something FUNDAMENTALLY different between blastomeres and ES cells.

So now, it's a religious opinion that there's some difference between blastomeres and ESCs?

Hat Tip to The Daily Transcript at ScienceBlogs.

Yamanaka has a conscience

“When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters,” said Dr. Yamanaka.

The New York Times article on Shinya Yamanaka, "Risk taking is in his genes," (free one time registration necessary) should get the headline-writer in trouble for a sad pun.

Instead, Dr. Yamanaka might be in trouble with the objectors to conscience. (No links, just look at today's posts - or the last two months of posts - the subject keeps popping up.)

People like John Gearhart, MD will want to "put pressure" on Yamanaka to write letters to Nancy Pelossi and the rest of the US legislators making the usual reactionary case for Federal funding for embryonic stem cell research in light of the successes with non-destructive research.

The NYT reporter, Martin Fackler, can't be too popular in the next few days for pointing out that the US laws and funding are not nearly as tight as those in Japan, due to moral objections in that country:

In 1999, his career got a break when he was hired by other universities, including Kyoto University in 2004, that were willing to give him a laboratory and more money. At about the same time, he said, he visited his friend’s fertility clinic. That visit inspired him to find a way around the moral issues that had bogged down stem cell research, not just in the United States but also Japan, where the Education Ministry put tough restrictions on embryo use.

In fact, restrictions are so tight that he says he cannot use human embryos at his laboratories here. Instead, research using human embryos is done at U.C. San Francisco, where he maintains a small two-person laboratory. He said he had never handled actual embryonic cells himself, and the American lab uses them only to verify that the reprogrammed adult cells are behaving as true stem cells.

“There is no way now to get around some use of embryos,” he said. “But my goal is to avoid using them.”

For a look at the science and bioethics slant on these revelations, see Wired Science (see the comments on this one), Blog.bioethics.net, Wesley Smith's Secondhand Smoke, and Jennifer Lahl's blog, "The Human Future."

Warnock Answers

Dame Mary Warnock has written an essay which was published in the November 29, 2007 issue of Nature, which appears to be an apologetic for her part in the establishment of the ethics of embryonic research in the United Kingdom. The bloggers at Women's Bioethics Project speculate that she wrote in anticipation of Parliament's review of the Human Fertilization and Embryo Authority.
The full essay is for subscribers only - but there's a 2006 article that describes the wider function of the committee, here.

What Warnock explains (but doesn't acknowledge) is that her committee did exactly what they accused the Catholics of doing: "answering in advance the very question we were asking."

The task was to justify embryo experimentation, posed to the Committee after it was proven that the embryonic Louise Brown was the born Louise Brown. They did the job they believed that they were assigned, and then projected their own act of "answering in advance" upon anyone who drew a connection between the moral worth of the embryonic Louise Brown and the born Louise Brown.

Ironically, Dame Warnock admits to no expertise in morality yet feels justified in rejecting the moral expertise of the Catholic Church simply because it is the Church. All the while complaining about the difficulty of pleading the case that the issue is one of morals.

I wonder whether we could get murder and rape prohibited by this committee.
From the Nature essay (emphasis is mine):

When in 1978 the first baby was born by in vitro fertilization (IVF) it was inevitable that there would be calls for the procedure to be prohibited. That science develops too fast for morality had become the cliché of the twentieth century. Wisely, the UK government decided to set up a committee from which to seek advice before legislating on such a complex and emotive issue.

The Committee of Enquiry into Human Fertilisation and Embryology was founded to examine the social and ethical implications of the new techniques. Therefore the committee could not be made up entirely of physicians and scientists. With some difficulty, 16 people — including me as the chair — were gathered to look at the problem from all angles. Our areas of expertise included social work, law and theology.

We were not a group of 'moral experts', with particular moral authority derived from our expertise. Rather, our entitlement to propose legislation derived from the fact that we had been set up by government and that we had been given the time and resources to do so. The only other requirement was that we should all be capable of formulating and listening to arguments.

The central and most controversial issue before us was whether or not research using live embryos should be permitted. There was little possibility of a moral consensus. If research were prohibited, IVF could not continue. It would have been too risky for patients.

When legislation seemed imminent in Britain, the Catholic Church published an instruction condemning IVF and research using human embryos. The Church stated that its instruction was based on "the criteria of moral judgement as regards the application of scientific research and technology, especially in relation to human life and its beginnings".

The Church claimed a right to regulate science in this area, because of its superior knowledge of morality. In sharp contrast, the committee's entitlement to issue moral advice to ministers derived from its having been set up to do so, and from its having a wide and non-partisan membership.

Prohibition of IVF did not seem to the majority of the committee to be a serious option, given its widespread welcome as an innovative remedy for infertility. We all regarded infertility as a serious malfunction, causing much distress. Instead, we proposed a strict system of licensing, backed up by the criminal law. Regulation was not a mere sop to science-phobia. There was a real danger that women, desperate to conceive, might be exploited, taken in by unrealistic promises and charged extortionate fees for futile or dangerous treatment.
Establishing what limits should be placed on embryonic research entailed a decision by the committee as to the moral and legal status of the live human embryo in vitro. Those who opposed the use of embryos in research could seek to demonstrate that it was morally wrong only by answering in advance the very question we were asking. They deemed that the embryo had the same moral status as any human being.

One of the most difficult tasks the committee faced was to get parliament to understand that the status of the embryo in vitro was a matter not of science but of moral decision. The novelty of the embryo in vitro meant that there could be no appeal to precedent or existing moral convention or to religious laws.

30 years later, the evolution of the HFEA regulations - through one mutation followed by another due to pressure to expand the limits of research - allow preimplantation genetic diagnosis, selection for "savior siblings" and against low risk genes, cloning and (most recently) licensing the use of non-human oocytes and human DNA for cloning experimentation.

Alabama Citizens for Life Link to LifeEthics

There's a link to LifeEthics.org at the website of Alabama Citizens for Life. I'm flattered that their "Stem Cell Primer" quotes this blog on the division of research into destructive and non-destructive.

Genes Cut Out of Reprogrammed Cells

Lots of people (here, here, and here, etc.) are commenting on the "Proof of Concept" by Jaenisch, et. al., in this week's ScienceExpress (early online publication before print) that showed gene modification to reprogram mouse cells in order to create blood line stem cells that would achieve gene therapy - or even, a cure - for sickle cell anemia.

(BTW, these mice are called "humanized knock in mice," meaning that the genes of the have been modified so that the their bone marrow hematopoietic or blood line stem cells have genes "knocked in" to produce human cells blood cells.)

To reduce the potential risk of tumor formation due to c-Myc transgene expression (13), iPS cells were infected with an adenovirus encoding Cre-recombinase to delete the lentivirus transduced c-Myc copies. One out of 10 iPS subclones (iPS #3.3) had deleted both transduced copies of c-Myc and was used for further experimentation (Fig. 2C).

Trust me, as soon as more labs figure out how to make use of these cells, to remove or repair - or to ensure there's no - damage from the insertion of the needed genes, the push for embryos will slow down. (I think it would even faster if Thomson and the California Institute for Regenerative Medicine could find a way to capitalize on adult stem cell research.)

Flash: Embryonic tissue more difficult to obtain than adult

This could liberate future researchers from relying on embryonic tissue, which can be more difficult to acquire.

"NatureNews," the news alert website for the journal Nature, has a news report (registration required) on a study published in the December 6 issue of the journal by researchers from Bonn, New York, Rhode Island, and Pennsylvania on regenerating heart muscle.

It is known that (in mice and assumed in humans) that embryonic heart stem cells or precursor cells (they're a bit more specialized than most of the "stem cells" we've been hearing about - cardiac myocytes (eCMs) and skeletal myocytes ("SMs") will bind to damaged areas of the heart and promote healing and division. However, the SMs have a much higher risk of irregular heartbeats called "ventricular tachycardia." (The "VTach" that causes most sudden deaths after heart attacks in real life and the dramatic scenes on TV.) Even though some people do have better heart function after treatment with their own SMs (from bone marrow or skeletal muscle), 15% of them die of VTach within 3 years.

The researchers found that the eCM's "coupled physically" to the damaged cells in the heart and exchanged electrical signals with the surrounding heart cells, so that they contracted in the proper rhythm.

The scientists (rather than deciding to pursue only eCM therapy) wanted to know why the SMs didn't do as well as eCM when it came to producing the correct rhythm. They discovered that the eCMs had more Cx43 than skeletal muscle. Mice were developed with gene therapy (using viral vectors to insert genes, a common technique used to create "gene mod" mice for research) so that the SMs of the mice express more Cx43 in skeletal muscle than normal. The mice hearts that received the modified SM's from these mice, when cultured and then injected into damaged hearts of other mice, did as well as the hearts that received eCMs.

The science is fascinating, but the irony of the report coming this week is pretty interesting, too. The author of the NatureNews report is truly unbiased or evidently didn't get the memo from the reactionary scientists this week.

(In case you're wondering, I don't get a memo from anyone other than the reactionaries' own blogs, and statements to the press.)

Wash this reactionary's mouth out with soap!

Bioethics.net compares the Bush administration's happiness about reprogrammed adult stem cells with that man, Mr. Clinton's, "I did not have sex with that woman!" and President Bush's statement "Mission accomplished," after our US troops captured Baghdad.

I'll accept the latter (at some future date, if the evidence supports it), but the first is at least as false as Clinton's wagging finger - and (speaking of Yuk factors) did we really need to be reminded of that?

The author, James W. Fossett (who is anything but "non-partisan") states that Yamanaka, the first to report reprogrammed adult cells in humans and mice is from Japan and wasn't affected by the US Federal funding limitations. He doesn't mention that Yamanaka's research didn't rely on the use of new embryonic cells, at all. Yamanaka took the information gleaned from animal research and the currently funded cells and moved to the front of all other stem cell researchers by pointing the way to the key to the production of stem cells from each patient who needs them - from his or her own cells.

Instead, Fossett is running scared due to the "rhetorical parity" from cell reprogramming and the possibility that the success in reprogramming cells will result in more reprogramming research!

Fossett doesn't mention that James Thomson's research using human Embryonic Stem cells (hESC). then human fetal cells harvested after abortions - and finally in skin cells harvested at circumcision of little boys - was funded by the National Institutes of Health, and that those hESC are the ones that supposedly are of no use.

Fossett also fails to mention of the new report by Yamanaka on the technique using only 3 inserted genes to the prior 4, and that the eliminated gene is the one that had scientists concerned about cancers.

I'm sure that he doesn't recall the "first transplantable lung cells" from hESC's by Texas researchers last year. These cells were developed by viral "transfection," also, and were lauded as "a platform that could potentially be useful in the development of spinal cord cells, heart cells, nerve cells and others.” These were neither the first or transplantable, but they did get much more notice than similar cells developed from umbilical cord blood cells without viral transfection.

That may be the problem: the proponents of hESC research are used to getting many times the publicity from hESC research than that received by the non-hESC researchers. And so, we get the concerns about "rhetoric."

There's those deceitful knee jerk reactionaries practicing their projection, again.

Knee Jerk Deceit (Embryonic Stem Cells)

The Washington Post has published an editorial by Alan I Leshner, Ph.D., and James A. Thomson, Ph.D. The op-ed is evidently in reaction primarily to Charles Krauthammer's November 30, 2007 column and blurs the line between fact and fiction in order to make a political plea to remove restrictions on funding for embryonic stem cell research.

Leshner is a psychologist, the Executive Director of the American Association for the Advancement of Science and the Executive Publisher of the magazine, Science. Science is the journal that published the two completely fabricated and retracted reports by Wu Suk Hwang about cloning, the letter attacking David Prentice, Ph.D., for his list of adult stem cell therapies, a letter by Dr. Prentice rebutting the attack, and yet another set of attacks-counter attacks. It is also the journal that published the article ahead of print by Thomson and Yu, et. al., describing the reprogramming of adult fibroblast skin cells on November 22, 2007, after the basic research was done using embryonic stem cells funded by the National Institutes of Health.

Thomson is the veterinarian and professor of anatomy at the Genome Center of the University of Wisconsin who first reported embryonic stem cells from human embryos and who confirmed that adult cells can be reprogrammed into embryonic stem cells. Thomson's institution oversees the NIH program for distributing the Federally funded embryonic stem cell lines and for training researchers to use those cells.

The editorial published December 3, 2007 is titled "Standing in the way of Stem Cell Research." Notice that there is no distinction made between embryonic stem (ES)cells and adult.

The opening sentence says, "A new way to trick skin cells into acting like embryos changes both everything and nothing at all." These stem cells do not act like embryos; they act like ES cells. According to Thomson in his report: "The human iPS cells described here meet the defining criteria we originally proposed for human ES cells."

Leshner and Thomson make the usual claim that ES cells can make all the cells of the body in order to treat spinal cord injuries, brain, heart and other diseases. They do not note that all these cells only come from embryonic stem cells in functioning intact embryos or with very limited, inefficient and difficult methods. In the lab, the stem cell cultures are not homogeneous clumps that can be be easily directed to the desired cells. Instead, the colonies contain cells at different stages of differentiation. Like adult stem cells and progenitor cells, the few stem cells that are amenable to some of the desired cell types must be selected and grown in special environments and nutrients.

No one has yet been able to guarantee that the cells derived from ES cells can be controlled. The risk of introducing a primitive, undirected cell line that will form tumors is the main reason that no one has yet attempted to use these cells in humans. The risk of uncontrolled - tumor causing cells is accompanied with the problem of immune rejection of transplants in patients. Researchers won't be able to obtain "patient specific" cells unless they are able to clone human embryos or learn to reprogram adult cells.

The letter points out that embryonic stem cells were used to help the researchers know how to grow human ES cells while claiming that funding has limited research, without admitting that research on those ES cells was indeed funded by Federal money. They write about the frozen embryos from IVF that would have been destroyed anyway but do not note that unless the donors of the gametes that join to become the embryo give informed consent prior to fertilization, those embryos are not eligible for ethical research. They don't mention the pleas for the intentional creation of new, disease specific embryos with the intention of harvesting research material to create '''disease specific" cell lines (like those made to "model" Fragile X syndrome and cystic fibrosis.)

The authors complain of restrictive funding that prevents young people from doing ES cell research. Then, they say that other countries don't have the same sort of problems and mention that Yamanaka did his research in Japan. In fact, there are other countries with much more rigid restrictions, and few have spent as much on ES cell research as we have here in the US. (Germany's policy actually forbids destruction of embryos.) Dr. Yamanakas' research would have qualified for Federal funding in the US since he didn't use embryonic stem cells at all in his experiments.

Leshner and Thomson tell us that it "remains to be seen whether reprogrammed skin cells will differ in significant ways from embryonic stem cells." It also remains to be seen whether human ES cells will ever be used in human beings.

Talk about reactionary science!

Edited 12/4/07 for punctuation, grammar - BBN

"embryo uber alles"

Ellen Goodman reminds us that it ain't over yet. As she said in her November 20, 2007 op-ed piece (Free registration at the Boston Globe may be necessary),

Democrats, on the other hand, may breathe a sigh of regret. The stem-cell controversy gave pro-choicers an iconic image of their enemy: someone who put the embryo uber alles. It gave progressives a poster girl in Nancy Reagan - and a poster boy in Michael J. Fox. Stem cells were to the left what partial-birth abortion was to the right, a way to frame a touchy issue and look like the reasonable center.

The next time someone has any questions about the source (or existence) of the divisive politics and agendas in the life issues, just point them to Ms. Goodman's observation.

But first, arm them with the explanation that there's no such thing as a "fertilized egg" (there's either an egg or an embryo) and note that the funding for embryonic stem cell research never existed before the President Bush's policy was set and was never maxed out on the Federal level.

Reactionary Scientists

I wonder how often our friend from Kyoto is planning to publish and what tweaks we'll hear about next week?

I also wonder how many of the comments about "must fund all" come from - or actually are a type of - the application of the sort of pressure that Gearhart told his audience in DC that he and others applied to induce Atala to write Pelosi?

I'm trying to get used to the idea of scientists as reactionaries.

Politics aside, I don't think any of the research could have gone any faster even without the "pressure" from either side. The basic science had to be done, and was.

Wait 'Till Next Week! (More iPS good news)

Dr. Yamanaka of Japan, the MD who made history last week by announcing that he had been able to obtain embryo-like stem cells fom adult skin cells called fibrobalsts. On Friday, November 30, has published a new report in Nature Biotechnology telling us how he was able to skip inserting the potential cancer causing gene, c-Myc.

At this rate, who knows what we'll have next week?

From The Scientist (online here):

In the current study, the researchers showed that pluripotent cells can be made from both mouse and human adult cells without introducing the c-Myc gene, by transducing just the other three. It's not that Myc isn't needed in the process, the authors noted in the paper; rather, they suggest that the other three genes may be spurring endogenous Myc activity. None of the 26 chimeras made from cells generated without c-Myc developed tumors within 100 days, compared to six out of 36 chimeras made from cells using all four genes.
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So far, too, efficiency with this triple-gene method is much lower than with the original four genes; half of the experiments without c-Myc did not produce pluripotent cells at all, while experiments using the four genes almost always yielded pluripotent colonies. "Does this mean that it now only works with a rare cell type?" Lovell-Badge wrote. "As always, many more questions are posed than answered."

The question is whether all fibroblasts are alike, or whether there is a smaller group of fibroblasts that are easier to induce to become "induced Pluripotent Stem" Cells.

If there are specialized cells in the skin that are easier to manipulate than others, this is good news for researchers and the patients who are looking toward stem cell research for treatments and cures.

Translation of Yamanaka, Yu "induced Pluripotent Stem Cells" (Revised)

Scientists who report their findings are expected to discuss the problems as well as the outcome of their research. This is usually found in the "Discussion," "Conclusions" or "Results" section of the paper. This is the best place to figure out what the researches intended, what they did and what the report means. (Then you go back and check to see if they proved what they "discussed." And then, you wait for other labs to confirm it.)

The actual (Takahashi et al., "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors," Cell (2007).) Cell article on reprogrammed adult fibroblast skin cells, the "induced Pluripotent Stem Cells) or "iPS," is available for free, here. The Science Magazine report about similar work by James Thomson from Wisconsin (the researcher who reported the production of human embryonic stem cells in the first place) is supposed to be published November 22, 2007. (Editorial note 11/30/07 – Science published the Thompson and Yu report the same day that Tamanaka's report was published, two days ahead of schedule. See my “translation,” here.)

To the best of my understanding, here's a translation into layman's terms about what the Takahashi/Yamaka report means:

While it took a lot of cells and more time than the researchers first expected because the human iPS grew much slower than the mouse iPS,

1. The cells that grew looked and functioned like human embryonic stem cells with a few minor differences,
2. They believe they proved that their technique is responsible for all the new pluripotent cells that were found in their cultures(there weren't any cells from another culture introduced accidentally or on purpose and which would make them look more successful than they were),
3. The cells could be directed to develop nerve cells and heart cells,
4. They were able to use several types of adult specialized cells to achieve iPS, and
5. The researchers suggest several possible ways to overcome the drawbacks of the process.

The authors believe that the inefficiency or the need to begin with lots of adult cells and wait a little longer for a substantial amount of human iPS should not be a "practical" problem because the adult cells are easy to obtain and labs all over the world should be able to reproduce their results. Since the technique should be well-funded (it qualifies for US Federal funding and is ethical, since no human beings have to die), the authors believe it will be possible for lots of researchers to work on them.

If I were to predict the future, I would anticipate banks of iPS - or even specialized or intermediate forms of cells that are produced from iPS - being stored for each of us, just in case. In the very long term, we will learn more about stimulating our on bodies' stem cells from research on these cells, so that we can repair or prevent damage without transplants or waiting for cultures to grow in the lab.

The major hurdle is that the cells were produced by the Recombinant DNA technique, using retroviruses in plasmids.

The retroviruses are a class of viruses that actually insert themselves into the DNA strands of animal or plant cells to become a part of that cell’s DNA and are copied when the cell reproduces. They are manufactured in the lab in the form of plasmids in order to carry genes into the experimental cells.

Plasmids are little bits of DNA, a mini-virus in a circle. Think of a chain with pairs of magnets or interlocking puzzle pieces that connect the ends and make a loop. When open, the plasmid becomes a strand of DNA which has ends that are "sticky.” When placed in a culture with mouse or human cells, the plasmids infect the cells and then move into the nuclei of the cells. The retroviral DNA is inserted or inserts itself into the DNA of the host cell because the sticky ends of the plasmid strand match or mate to certain areas of the host DNA.

Plasmids can be manufactured to carry copies of genes that researchers want to insert into the DNA of experimental cells. The technique is common in commercial and experimental labs for at least the last 30 years. In fact, "Recombinant DNA" is used to induce strains of bacteria and yeast cells in cultures to manufacture vaccines like the flu and Hepatitis B vaccine and the insulin used by diabetics these days. The particular retroviruses used by Tamanaka are said to be "strongly silenced in humans." In other words, they don't normally get reproduced as viruses when the cell divides. Once they are taken up in the cell DNA, the viruses used in research don't break out to become infectious viruses, again. However, some of them can induce the cells to form tumors or cancers if injected in an animal or human.


One of the possible problems that the article notes is that the new iPS cells each had several copies of the retrovirus included in their DNA. There is a concern that these bits may be responsible for the tumors that were seen in the mice used in the experiments. Before iPS can be used in humans, it will be necessary to learn to remove all the viral particles or to learn to make the cells without viruses that can cause tumors. Otherwise, there is a risk of causing cancer in patients.

The researchers note that another group of scientists have already reported that it is possible to insert one of the genes without using retroviruses and that the hope is to either find a way to insert the other three genes or to remove all traces of the virus.

There's also a suggestion that what they are actually inducing to grow is a sub-set of fibroblasts with the tendency to become embryonic-like stem cells.