Adult stem cells in MS for reversal

In Multiple Sclerosis (MS), the immune system of a patient turns on his or her nervous system, destroying the myelin sheaths that serve as insulation around nerves, disrupting the transmission of nerve signals. The myelin damage often occurs in a patchy manner, at first. See the Medline Plus page from the National Institutes for Health for more information, including a patient tutorial in English and in Spanish. The Journal of the American Medical Association has a similar patient education page in pdf.

There have been trials using adult stem cell treatments in the form of bone marrow transplants and injection of adult stem cells in different manners for several years. (See ClinicalTrial.gov for some of these - if my search lapses, search "stem cell multiple sclerosis.)

The March issue of Lancet Neurobiology reports (Free access to the abstract) success from research at Northwestern University using the patients' own bone marrow stem cells, after harvesting those cells, preserving them, and then using chemotherapy to destroy the immune system before replacing the patient's stem cells. A review of the study is at the Science Daily and at this blog, Science Codex.

Here's the information on this trial from Clinical Trials.gov.

Any sort of bone marrow transplant is dangerous due to the lost red blood cells, platelets (to make blood clots), and the white blood cells that function as the immune system. This trial was set up to preserve all but the immune system. While it's still not a procedure to take lightly, it appears that the researchers at Northwestern have made it safer.

"Tea-bag" Adult Stem Cell Treatment for Stroke

British researchers report an amazing recovery for a 49 year old man who suffered a hemorrhagic stroke on October 15, 2008. The researchers at the company, "Biocompatibles," used adult stem cells from a healthy donor. The cells had been engineered to cause them to produce a protein that helps prevent "programmed" cell death (even after the bleeding stops and the pressure is removed) and embedded in tiny beads that had been sewn up in a cloth "tea-bag."

From the press release, published on the Medical News Today Neurology and Neuroscience website:

Stroke is one of the leading causes of death in the elderly population in the developed world. The incidence rate has been reported as 145 per 100,000. Hemorrhagic stroke is responsible for ~15 to 20% of all stroke and it is the least treatable form of stroke. It is associated with the highest morbidity and mortality rate of all stroke with only 44% of affected patients surviving the first 30 days. Only 20% of these survivors regain functional independence. The cascade of events starts with the sudden rupture of a blood vessel in the brain, causing haemorrhage and pressure inside the skull. Surgery may be used to relieve the pressure; but the haemorrhage causes a longer-term process of programmed cell death, or apoptosis, and it is this that causes the lasting neurological damage.

The CellBeads™ are delivered directly to the injury site during the surgery. They are programmed to deliver CM1, a proprietary version of a naturally occurring protein, GLP-1, which has been shown to have powerful anti-apoptotic effects. The delivery mechanism is a cluster of human adult mesenchymal stem cells obtained from a healthy donor and encapsulated in alginate beads. The cells are genetically engineered to produce the protein, which is delivered continuously, directly to the injury site. The alginate beads protect the stem cells from the body's immune system, which would otherwise destroy the foreign cells. CellBeads™ are transplanted within a retrievable mesh device and are removed completely after a treatment period of 14 days. Retrieval of the implant prevents possible long-term side effects from the transplanted cells.

The research is a "Phase I/II" trial, which means that the doctors and scientists are actually testing the safety of the treatment, and not the actual effectiveness of the treatment, itself. In other words, "does the treatment do more harm than good."

The CEO of Biocompatibles, Crispin Simon (that name is as British as tea bags), spoke to a Reuters reporter for a story published at Forbes online, stressing that the patient is young and other wise healthy, and had the standard of care for hemorrhagic strokes, surgery to relieve the pressure from the blood on the cells around the stroke. 10% to 20% of patients have similar recovery, without the Biocompatible beads.

Still, the report is a welcome source of hope for anyone who has watched and waited helplessly after a patient or a loved one had a hemorrhagic stroke.

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.

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?"

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.

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.

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.)

Embryonic Stem Cells in humans?

There are stories about embryonic stem cells being used by a doctor in India, Dr. Geeta Shroff who works at in vitro fertilization clinic. Dr. Shroff has not published her work at Nu Tech Mediworld, will not allow other researchers to examine her cells, cultures or techniques, and the research was rejected by the Indian Council of Medical Research (ICMR). According to this article from the UK's Guardian, Dr. Shroff is a fertility specialist who became famous for a technique allowing the determination of a baby's sex without a scan or amniocentesis. (It's illegal to check on the baby's sex in India, now, because of the numbers of baby girls who were aborted in that country.)

Wise Young, M.D., Ph.D. is an expert from the W. M. Keck Center for Collaborative Neuroscience at Rutgersin treatment and research on Spinal Cord Injury (SCI) and he is my hero because he runs a bulletin board for people from all over the world who are looking for hope for their SCI. Dr. Wise and I disagree on embryonic stem cell research, but we do agree on this woman's methods:

1. There is no evidence that Dr. Schroff is injecting embryonic stem cells. The fact that she is so secretive about the cells after having done 150 patients suggests that she in fact is not injecting embryonic stem cells. Why not show the cells and describe them? She does not describe how she pre-differentiates the cells, if at all, before transplantation. The lack of such information is very suspicious.

2. I wonder how much Dr. Shroff knows about spinal cord injury and how rigorous she has been in examining the patients, whether the patients were incomplete or complete before the surgery. She probably assumes that no patients walk after spinal cord injury.

3. The fact that this "works" on every disease that she has tried it on is also very suspicious. There is no such thing as a universal treatment.

There's this long thread at "Care Cures" concerning young people who have had the doctor's "shots" over the last two years. Look at the last 5 pages, with stories from people who believe the treatment is a scam.

Dr. Shroff says that she experimented on embryos donated to her by patients at her IVF clinic and that one of those embryos yielded what she calls a very successful line that she has been using in patients. The patients say that they receive shots of the stem cells over months, while they undergo therapy at the clinic.

There's not much information on the Web, nothing at all at the National Library of Medicine listing of scientific and medical research, the National Biotechnology Information Center, Pub Med, and no listed articles by Dr. Schroff or clinic websites that can be found with a Google search, just a few stories from individuals and a few news articles.


Here's the website of a woman, Amanda, who received treatment in India in August, 2007. one from the Skye news service about a woman from Australia. This article from the Australian "60 minutes," has a discussion with another researcher, Hans Keirstead, Ph.D., who is described as a "wiz-kid" associated with the Christopher Reeve Foundation at the University of California-Irving, who has published quite a bit of basic research in animals with embryonic stem cells and who claims that Dr. Shroff is unethical for using humans as her "guinea pigs."

Biographic article on Yamanaka

Here's a cute biography of Shinya Yamanaka, lead researcher from the Japanese team that reported reprogramming of adult cells into embryonic-like stem cells.

As an M.D. myself, I find it interesting that, unlike veterinarians James Thomson of Wisconsin and Time Magazine Person of the Year, Hu Suk Hwang, Dr. Yamanaka is a human doctor, trained in orthopedics:

Yamanaka has spent most of his life in western Japan. A native of Osaka, he earned his medical degree at Kobe University and a doctorate in pharmacology at Osaka City University.

After completing his residency in orthopedic surgery, Yamanaka headed to the University of California, San Francisco, to do postdoctoral studies that laid the groundwork for his current research.

He does express concern about the possible uses of his research by unethical researchers:

Yamanaka worries about the road some people might take.

"We need to come up with some sort of rules about what kind of cells can be used and to what ends. Otherwise, someone may put this technology to use in troubling ways,” Yamanaka said.

The research's ethical and social implications are never far from the table in Yamanaka's laboratory, said Kazutoshi Takahashi, a junior professor who participated in the project.

"The potential problems are cut down when you use this method given that we don't have to use embryonic stem cells, and that's a good thing,” Takahashi said.

Since the debate isn't yet over about ethical vs. unethical stem cells and since some people (like embryonic and fetal stem cell researcher and sometimes guest Science editor, John Gearhart, MD) have admitted to putting pressure on researchers to make sure that they follow the official line to pursue "all promising areas" (echoed here by the stem cell industry trade association organization, BIO) kinds of stem cell research, I hesitated to post this link and the quotes. But someone should record the true "debate."

UTexas: Modified virus fights stem cell cancer

Viral gene therapy (similar to techniques used in the stem cell breakthrough last week) has been used by University of Texas MD Anderson Cancer Center researchers in animal models and reported in the September 19, 2007 issue of the Journal of the National Cancer Institute. From MD Anderson:

Since 2004 scientists have found that brain tumors are driven by haywire stem cells that replicate themselves, differentiate into other types of cells, and bear protein markers like normal stem cells.

"Research has shown that these cancer stem cells are the origin of the tumor, that they resist the chemotherapy and radiation that we give to our patients, and that they drive the renewed growth of the tumor after surgery," Fueyo said. "So we decided to test Delta-24-RGD against glioma stem cells and tumors grown from them."

Researchers used a virus to infect the cells of aggressive tumors of the cells that support brain cells, glioblastoma multiforme. Gliomablastomas are 60% of brain cancers and patients have a survival rate as short as 2 to 3 months, with less than 10%-25% survival after 2 years even with current aggressive therapy. The virus is modified so that it is "selective" for cancer: it only infects the cancer tumors and cannot infect others.

The team first developed mice with transplanted human brain cells derived from stem cells found in four samples of glioblastoma multiforme. The researchers then developed a customized virus, Delta-24-RGD, to fight the cancer. According to a 2003 MD Anderson press release on the trials, the virus infection inserts copies of a certain gene, retinoblastoma protein (Rb), that acts as a "brake" on the cell duplication system of the cell. In order to make the therapy more efficient and safer, the virus also insert a gene to for a cell surface receptor, a sort of "docking" area on the outside of the cell.

The cell surface receptor for viruses is one of the ways that we are studying to fight both cancers (see this free article from this month's JNCI) and viral infections, themselves. The goal is vaccinations to affect genetic causes of cancer (as in these two reports) or to prevent viruses from binding to the cells and infecting them in the first place.

Translation of "Induced Pluripotent (Human) Stem Cells"

Please see the revised version of this post, published November 30, 2007.

Reprogramming Stem Cells - Links to Articles

I got the authors backwards. Here's the corrected version:


Takahashi et al. (including Yamanaka), Cell Online, free pdf.

There's a "Preview" article in pdf here.
Still waiting for Science to post Thomson's report online.

Embryonic Stem Cells from Patient's Own Adult Stem Cells

Well, they did it!

From Reuter's, UK:

WASHINGTON (Reuters) - Two separate teams of researchers announced on Tuesday they had transformed ordinary skin cells into batches of cells that look and act like embryonic stem cells -- but without using cloning technology and without making embryos.

Their breakthroughs could make possible the long-sought goal of tailor-made medicine, but without the political, scientific and ethical roadblock of using human embryos.

Both teams call the new cells induced pluripotent stem cells and say they look and act like embryonic stem cells -- the master cells that give rise to every cell and tissue in the body.

. . .

James Thomson of the University of Wisconsin in Madison and colleagues reported their finding in the journal Science while Shinya Yamanaka of Kyoto University in Japan and colleagues reported theirs in the journal Cell.

I haven't read either article, so -- long pause ---

A brief history of cloning

Steve Connor of the The Independent, from Britain, tells us the history of cloning.

But first, the "good news:"

A technical breakthrough has enabled scientists to create for the first time dozens of cloned embryos from adult monkeys, raising the prospect of the same procedure being used to make cloned human embryos.

Attempts to clone human embryos for research have been dogged by technical problems and controversies over fraudulent research and questionable ethics. But the new technique promises to revolutionise the efficiency by which scientists can turn human eggs into cloned embryos.

It is the first time that scientists have been able to create viable cloned embryos from an adult primate – in this case a 10-year-old male rhesus macaque monkey – and they are scheduled to report their findings later this month.

The scientists will also demonstrate that they have been able to extract stem cells from some of the cloned embryos and that they have managed to encourage these embryonic cells to develop in the laboratory into mature heart cells and brain neurons.

Scientists who know of the research said it was the breakthrough that they had all been waiting for because, until now, there was a growing feeling that there might be some insuperable barrier to creating cloned embryos from adult primates – including humans.
*****

The Oregon team, working with a group in China, has so far produced about 100 cloned embryos that have been transferred into around 50 female macaques, but none has resulted in a full-term pregnancy, he said.

"It's possible that we're still just having bad luck. We're producing may be one in 20 or one in 30 cloned blastocysts that are 'normal' and capable of producing a pregnancy and we just haven't got them into the animal recipient at the right time to allow implantation and pregnancy to occur," Professor Wolf said.

"The focus now is going to be on therapeutic cloning and using the non-human primate as a paradigm for therapeutic cloning for what you might be able to do clinically," he said.

"We're the first to do it, although it's a tainted subject because of the fraudulent research that came out of South Korea. One can never be sure but there may be some validity to what the South Koreans did. But this would now be the first documented therapeutic cloning in a primate," he added.

A brief history of cloning

The monkey-cloning technique is the same basic procedure that resulted in Dolly the sheep. The nucleus of a healthy, unfertilised egg is removed and another nucleus from the mature skin cell of an adult animal is placed inside the egg. With careful timing and the use of electrical pulses, an embryo can be created which is a genetic clone of the skin tissue donor. It is possible to implant embryos created in this way into the womb to produce cloned animals. This so-called 'reproductive cloning' of humans is illegal in Britain and many other countries. However it has been applied to a range of animal species, including:

* Cow: Many domestic cattle have been successfully cloned. First attempt to clone an endangered species was Noah, a rare gaur ox, which was cloned in the US in 2001 but died 48 hours after birth

* Mouse: Cumulina was a common brown house mouse, cloned from adult cells at the University of Hawaii in 1997. She survived to adulthood and produced two litters, before dying in May 2000

* Horse: Called Prometea, the first cloned horse, born in Italy in May 2003

* Cat: A kitten called CopyCat was born in 2002 in Texas, and gave birth to three kittens by a natural father in September 2006

* Dog: Snuppy, born in South Korea. Doubts about its authenticity were dispelled by DNA tests. The group has also cloned two wolf cubs, called Snuwolf and Snuwolffy using the same procedure. Cloned Afghan hounds named Bona, Peace and Hope have also been born.

Review: What we know about stem cells

The Journal, Stem Cells, has published a free open access article about those cells that become the different blood cells, including red blood cells, white blood cells and platelets, entitled "Concise Review: Hematopoietic Stem Cells and Tissue Stem Cells: Current Concepts and Unanswered Questions" by Donald Metcalf, MD, of Australia.

An interesting point from this article is the current controversy about the definition of "stem cells." Dr. Metcalf gives his definition and notes that some cells now called stem cells are actually better described as "self proliferative" progenitor cells, which have been committed to only fewer lines of cells.

Which will be important to understand the controversy that surrounds another type of stem cell, which is described in another, newer article published this week online in advance, entitled, "Concise Review: Mesenchymal Stem/Multi-Potent Stromal Cells (MSCs): The State of Transdifferentiation and Modes of Tissue Repair - Current Views" by Donald G. Phinney and Darwin J. Prockop of the Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA.

These adult stem cells are found in most organs and tissues in the body including umbilical cord blood, skeletal, muscle, fat, joint fluid, blood and the cells surrounding the blood vessels, the pulp in teeth, and amniotic fluid. (They have also been harvested from aborted infants.) In the body, they are known to become bone cells, fat cells, and cartilage. When they are grown in the lab, they form a wide variety of tissues depending on the conditions in which they are grown. They can be induced to form cells that function as nerve, lung tissue, retinal pigment cells, blood vessel cells, and repair kidneys and hearts.

However, you may read that these cells are not as "plastic" as embryonic stem cells, that it's hard to study them and cause them to form the exact cells that are desired. While it's true that they do not form "all the cells in the body," they can be induced to form a wide range of cells and tissues and it's no harder to control the development of these cells than it is to control embryonic stem cells. They may in fact be different types of progenitor cells, depending on the source, but there are an awful lot of sources. And they don't require the destruction of a human life.

Rao: Adult Stem Cells "soon to be on the market"

The journal Stem Cells has published an Open-Access review by the former NIH director, Mahendra Rao, MD, PhD, covering last month's "Adult Mesenchymal Stem Cells in Regenerative Medicine Conference" at the National Center for Regenerative Medicine in Ohio.

Another review with summaries of some of the individual talks as well as the history of the National Institute for Regenerative Medicine and Dr. Arnold Caplan's part in founding both the NIRM and Osiris, can be found at Medscape.

Mesenchymal stem cells (MSCs) can be found in bone marrow and other organs. MSCs are proving to be multipotent, meaning that they can be induced to give rise to different types of cells.


Speakers at the conference included virtually every "big" name in stem cell research, including Dr. Rao, Caplan, Anthony Atala, Catherine Verfaille, and Paul Simmons. The program covered the history, basic science and techniques involved in harvesting and culturing mesenchymal stem cells. There were reports covering the multipotent nature of MSC's and some of the treatments and commercial applications that are in use or will soon be available. One company, Osiris, has been in phase III of some clinical trials of stem cells for treatment of heart disease, graft vs. host disease, Crohn's, and cartilage and tendon repair. Veterinarians are already using MSC's to treat horses and other animals.

Take a look at the last page of the review which contains a graphic covering the wide range of topics.

Pay for embryo destruction added to Senate Bill

Senators Specter and Harkin, in the Senate Appropriations Committee, have added funding for research on embryos destroyed in research between the August 9, 2001 cutoff point and June 15, 2007 to "a must-pass bill for the Labor and Health and Human Services".

The Bill must make it through the Senate, the House and the possible "conference committees" (where compromises between the two bodies are worked out) before it can be sent to the President.

From the Houston Chronicle:

The pushback began Thursday. The Senate Appropriations Committee approved a must-pass bill for the Labor and Health and Human Services departments that includes permission to use federal funding for embryonic stem cell lines derived after Bush in 2001 banned taxpayer dollars from being used on new studies of that kind. Voting no were Sens. Ben Nelson, D-Neb., Sam Brownback, R-Kan., and Judd Gregg, R-N.H.

The provision, proposed by Sen. Tom Harkin, D-Iowa, would allow taxpayer dollars to be spent on research on human embryonic stem cell lines derived prior to June 15, 2007 — moving the date of Bush's August 2001 ban on public funding for such research up by nearly six years. The overall bill now moves to the full Senate for debate later this year.

Research on stem cell lines derived in the interim would be eligible for federal funding. The new provision also would add ethical standards to be used for selecting embryos to be studied using federal funds.

The research funds are not in anyway necessary. The creation and destruction of embryonic humans for their parts is unjust.

Take a listen to some of the poorest reasoning I've ever heard for Federal funding at National Public Radio. R. Alta Charo, who works for Planned Parenthood and calls "neocons" part of the "endarkenment," believes that the Feds will"dwarf" the $3 Billion that California has budgeted for destructive embryo research!

The Veto vs. the Big Picture

Yesterday, the President vetoed a Bill that would have "enhanced" some human embryos right out of life, while pledging to save more lives, now.

According to the White House Press Release reporting on President Bush's speech, he was joined by Dr. William Hurlbut and Dr. Don Landry. Both of these men are proponents of alternative means to harvest cells that could be as "plastic" as embyronic stem cells - in fact could be embryonic stem cells - without destroying or harming embryonic humans.

The President got his priorities right as well as his science.

Congress has sent me a bill that would overturn this policy. If this legislation became law, it would compel American taxpayers -- for the first time in our history -- to support the deliberate destruction of human embryos. I made it clear to Congress and to the American people that I will not allow our nation to cross this moral line. Last year, Congress passed a similar bill -- I kept my promise by vetoing it. And today I'm keeping my word again: I am vetoing the bill that Congress has sent. (Applause.)

Destroying human life in the hopes of saving human life is not ethical -- and it is not the only option before us.

First, he states that no matter how "useful" the harvest of human embryos, it is not ethical and he will not support the purposeful destruction of some non-threatening humans for the benefit of others.

We call these humans "innocent,"but this is one of the words that will be attacked when the opposition reports on the story. When you hear or read about someone ridiculing the notion that the President is protecting "innocent" embryos, you could ask them how any embryo ever harmed them enough to deserve to die.

It might also be useful to remember that there was protest in the '70's over the institution of in vitro fertilization and the creation of human embryos out side of the body. We were promised that these youngest members of our family would only be loved, wanted and implanted, never used as experimental fodder.

Well, that promise lasted about as long as the promise to use only "left over" embryos, a promise broken at Universities around the US, at least very remotely supported by our taxes and society.

This week, we've seen an increased push for that Country's regulatory board to allow human-animal hybrid embryos, using human DNA and animal eggs. We've heard about one researcher's cloning of Primates using rhesus monkey skin cells in order to successfully create embryos, and then to destroy and harvest two lines of embryonic stem cells. (Note, everyone's calling it "cloning," although watch the way the topic is quickly moved to "blastocyst" from embryo.) There'll be quite a bit of hype about how this will advance human cloning. There's even a new report that indicates that 60% of IVF parents would donate their embryonic children to research if they knew the embryos would be used to harvest stem cells.

Please watch the language and the route of the discussion. We'll hear about the "waste" of embryos that are left over, but no suggestions that we make fewer embryos. Instead, immediately following, there'll be a plea for funding to create more, specific embryos in order to study disease. Disease which is not seen at the embryonic stage of life, by the way. we'll hear about the "necessity" for "patient specific stem cells," using "SCNT" (yes, it's cloning, see the articles on the cloned rhesus monkeys) to create new blastocysts and new cell lines to match each patient and each disease. You'll probably read the new term, "blastocystic" or "blastocyst" stem cells, being touted by at least one author.

Men have always killed each other and they probably always will. There's just no need to hand them US Federal tax dollars for doing so.

Hiatus (Over, I hope)

I haven't been blogging - I've been lobbying and working, instead. Whether in Austin or at work, my access to the blog is spotty. And I worried that anything I wrote might get in the way of some bills we were fighting for.

Unfortunately, the Texas legislature is self-destructing and virtually none of the pro-life, pro-family bills made it through.

One of the bills I was lobbying for contained amendments to the Texas Advance Directive Act (TADA) that would have increased protection for patients, prevented the removal of artificial hydration and nutrition, and more than doubled the time that doctors had to give medical treatment that they and others deemed "inappropriate." An improved process for communicating with families and a liaison between the family and the doctor was in the bill, which would have also added funding for facilities that offered complex medical treatments, such as dialysis for comatose patients, which simply don't exist in Texas. For two more years, we have the same law and the same arguments.

I do expect some of the recommendations, such as a dedicated liaison and improved communications to be adopted voluntarily in hospitals, as the good ideas that they are.

The Bill to limit embryonic stem cell research also failed, but we did get a brochure to explain the options available for donating cord blood and held the line on expanding unethical research, since several "clone and kill" bills were blocked.

Billions and Billions of stem cells (or ACT kills more mice needlessly)

Once again, ACT is hyping research that duplicates work already done using non-embryonic stem cell research. The only thing new is the possibility that they have come up with a way to make "Billions" of the plastic cells.

Ok, maybe we learned something from Advanced Cell Technology's Robert Lanza's latest human embryonic stem cell report published on line (free) prior to print in Nature Methods, "Generation of functional hemangioblasts from human embryonic stem cells." Perhaps the method of growing the cells without animal or human serum will prove useful.

This time, ACT is hyping their development of "hemangioblasts," the stem cells that become blood cells and the cells that make up the blood vessels, and the big claim is that the researchers at Advanced Cell Technology have a technique for making "billions and billions" of cells. Their own introduction explains that the group has not developed a new line of cells or proven anything new as far as vascular repair goes:

Although progenitor cells have recently been discovered that can enter the circulation in response to vascular injury and ischemia (1–5), defining and isolating these cells has proven problematic. Circulating bone marrow–derived cells have also been shown to be important in normal physiologic maintenance and repair of the body’s vasculature (6,7) with approximately 1–3% of endothelial cells at any one time being bone marrow–derived. Furthermore, the entire hematopoietic system has been hypothesized to originate from a transient population of hemangioblasts restricted to embryogenesis (8,9). But recent evidence suggests that hemangioblasts or more mature endothelial progenitors may also exist in adult tissues and umbilical cord blood (2–4,10,11).More direct proof for their existence was provided when the in vitro equivalent of the hemangioblast was isolated using a mouse embryonic stem cell differentiation system (12,13). Recently a human hemangioblast cell population derived from hES cells was also identified using a procedure that consisted of serum-free differentiation in a mixture of cytokines followed by expansion in serum-containing medium (14). To date, large-scale generation or functional assessment of hemangioblasts has not been achieved in any of these systems. Here we show that large numbers of what appear to be a distinct population of progenitor cells with both hematopoietic and vascular potential can be efficiently and reproducibly generated from hES cells using a simple two-step procedure with different supplements under fully serum-free conditions.

Here's those references, please note the titles:

1. Rafii, S. & Lyden, D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat. Med. 9, 702–712 (2003).
2. Grant, M.B. et al. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal eovascularization. Nat. Med. 8, 607–612 (2002).
3. Bailey, A.S. et al. Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells. Blood 103, 13–19 (2004).
4. Cogle, C.R. et al. Adult human hematopoietic cells provide functional hemangioblast activity. Blood 103, 133–135 (2004).
5. Otani, A. et al. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat. Med. 8, 1004–1010 (2002).
6. Crosby, J.R. et al. Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ. Res. 87, 728–730 (2000).
7. Hill, J.M. et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med. 348, 593–600 (2003).
8. Wagner, R.C. Endothelial cell embryology and growth. Adv. Microcirc. 9, 45–75 (1980).
9. Park, C., Ma, Y.D. & Choi, K. Evidence for the hemangioblast. Exp. Hematol. 33, 965–970 (2005).
10. Loges, S. et al. Identification of the adult human hemangioblast. Stem Cells Dev. 13, 229–242 (2004).
11. Pelosi, E. et al. Identification of the hemangioblast in postnatal life. Blood 100, 3203–3208 (2002).
12. Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J.C. & Keller, G. A common precursor for hematopoietic and endothelial cells. Development 125, 725–732 (1998).
13. Kennedy, M. et al. A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386, 488–493 (1997).
(Emphasis is mine)

As I said, the main claim in the article is that the ACT researchers made a large number of hemangioblasts, and set about proving that they were, indeed, hemangioblasts, through experiments on mice, which all had induced injuries and which were sacrificed for autopsy.

However, what do we read in the tabloids science mags?

From Scientific American.
"New Recipe for Powerful Stem Cells Promises Greater Insight."

Other groups had discovered hemangioblasts in mouse and human embryonic cells as well as in adult human bone marrow and umbilical cord blood. But they were unable to harvest them in large enough numbers to evaluate the cells' healing properties.

And from Technology Review, "Stem Cells Repair Blood Vessels: A new method to boost growth of blood vessels with stem cells could improve cell therapies for diabetes and heart disease."

And last, but not least, from Reuters, UK, "Embryonic stem cells can repair eyes, company says."

"For example, we injected the cells into mice with damaged retinas due to diabetes or other eye injury. The cells (labeled green) migrated to the injured eye, and incorporated and lit-up the entire damaged vasculature. The cells are really smart, and amazingly, knew not to do anything in uninjured eyes."

The researchers killed the mice to check the cells' progress, so they do not know the long-term effects.

What none of the articles mention is the ongoing studies using non-embryonic stem cells to do what ACT claims its embryonic stem cells will do.

There was this report in the American Journal of Pathology in 2006 and this one from 2004, published in the Journal of Clinical Investigation about using a patient's own bone marrow cells to repair eye injury. Both used mouse models.

There is also the Austin, Texas trial that I reported on last week, which is using donor bone marrow cells. And there are several studies, including one using the patient's own stem cells to treat "Critical Ischemic Limb," at Houston, Texas' Stem Cell Center at St. Luke's Hospital.

It appears that this is just one more example of hype and hope about cells that have already been studied - and even used in humans - when someone (ACT, too often) claims to have a new study proving that they have generated human embryonic stem cells of some sort or other and to have "cured" some disease. (in mice, if at all.)

Austin Texas Patients In Adult Stem Cell Research

The Austin, Texas TV station, KEYE, has a report on the research trial using donated adult stem cells from bone marrow in patients within 10 days of a heart attack. (I've highlighted the part about the bone marrow.)

Seema Mathur
Reporting

(CBS 42) AUSTIN

A clinical stem cell trial involving Austin patients has some doctors saying it may change medicine forever.

The trial involves heart attack patients using adult stem cells. The stem cells are from the donated bone marrow of healthy adults.

The trial is in its first phase, with just 10 sites around the nation. Doctors are already saying the results hold the promise of doing what has never been done before, rebuilding heart muscle of heart attack patients.

Ben Calvo, a math teacher, was willing to take what he considers a calculated risk. He's one of 53 heart attack patients in the nation taking part in an adult stem cell clinical trial.

“I don't feel like a guinea pig,” Calvo said. “I don't want to say I feel super human, but I feel just great.”

Dr. Roger Gammon is director of research at Austin Heart, cardiologist providers in Central Texas. He says that in the double blind study, within 10 days of a heart attack, some patients received adult stem cells from donated bone marrow and other patients received a placebo.

“We hang a bag that has millions of stem cells in it,” Gammon said. “They infuse through the vein and travel to where there is an injury. It's just a simple intravenous infusion over 30 minutes.”

Calvo thinks he received the real thing. According to recent images of his heart, so does Gammon.

“Now, his whole heart is moving well,” Gammon said.

The image of Calvo’s heart is amazing because, up until this study, nothing could repair damaged heart muscle.

“They don’t just patch the problem, they actually become heart tissue that starts beating,” Gammon said.

“I feel that I can breathe better,” Calvo said.

Gammon says there was no rejection. He says some patients also had unexpected improved lung function and less irregular heartbeats.

“There seems to be an amazing homing mechanism with these cells to where they can figure out where there is an injury in your body and they go there and start to heal it,” Gammon said.

Calvo believes healing heart muscle is exactly what he experienced. Calvo also had some stents put in after his surgery.

Before this can become an approved treatment, many more people need to be studied to see if the results continue to be promising. But if they do, Gammon suspects this treatment may also help other inflammatory conditions like Alzheimer’s.

(© MMVII, CBS Broadcasting Inc. All Rights Reserved.

No dissent allowed in Nature Neuroscience journal

I received a reply to my letter to the editors at Nature Neuroscience yesterday:

9th May 2007

Dear Dr. Nuckols,

Thank you for your letter to the editor of 3rd May. Having had a chance to consider it, we do not feel that this subject would be appropriate for our letters section. We think that these matters would be more appropriately discussed on the Nature Neuroscience blog, Action Potential, given the intense pressure for space on our pages. We have made the editorial freely available and posted links to the relevant original articles at http://blogs.nature.com/nn/actionpotential/2007/04/does_human_embryonic_stem_cell.html, and we invite you to post your response there.

Yours sincerely,

Annette Markus, Ph.D.
Associate Editor
Nature Neuroscience

I've posted my letter, but it's awaiting the moderator's approval.

Just in case, here's that letter and my comment:

Frankly, what is the "scientific" justification for declaring any argument "anti-science"?

The editors suggested that I post my letter to them to this board. Here it is:

To the Editors:

I was surprised to read an unattributed editorial in the April, 2007 Nature Neuroscience, ("Shaky arguments against stem cells") critical of the essay in First Things by Maureen Condic, Ph.D. While emphasizing the "conservative Roman Catholic" background of the ethics journal, she is accused of "spinning" science "to fit an anti-scientific purpose." It appears that NN's anonymous editors' purpose is much less scientific that Dr. Condic's unless we're discussing political science.

There is no expression of disagreement about Dr. Condic's facts or her credentials to comment on the subject of embryonic stem cells and it is noted that she does not engage in making "fundamental moral arguments." Those anonymous authors seem most offended that she commented at all. The editorial, published without identifying the authors, reflects a deep bias and a "spin" of its own, discrediting your journal and "distorting the state of the field," indeed.

Beverly B. Nuckols, MD
New Braunfels, Texas

(Edit 5/12/07 to fix a broken link)

(Un)Ethical Science Journals

I guess the first question should be, "Where is the scientific and ethical justification for demanding public funding of science without public restraints?"

The next is, "When there is public disagreement, what is the ethical way to conduct the discussion about the disagreement?"

I'm sure that the answer to the second is not "hit and run."

Wesley Smith adds a new bit of information to the story I wrote about last week, concerning an attack on Maureen Condic, PhD, for her informational article on the lack of promise of embryonic stem cells.

It seems that that the journal Nature Neuroscience has refused to allow Dr. Condic, a respected neuroscientist herself, to respond to the editorial on their pages.

Why, Wesley, the editors didn't display enough courage to sign their names. I'm not surprise that they continue to take the less courageous road.

"Sneaky" Texas Legislator

Perhaps this article, written by an Associated Press writer, should be receive the Yellow Brick Award. (Should I put "copyrighted" here? No, there's others, although most - like the award for finishing the obstacle course at Quantico - are awards for achieving the impossible, not for misdirection.)

Someone is practicing distraction and projection by calling a vote in the Texas House State Affairs Committee a "Sneak attack."

Friday's vote came after a committee meeting that began Thursday and lasted through the night. Critics said the vote came hours after testimony concluded and while the committee was focused on an unrelated bill.

"Those of us who rely on the hope stem cell research holds, and anyone who cares about an open public dialogue, should be outraged at the manner in which the vote was taken on Friday afternoon — without discussion and while two members opposed to the bill were absent," said Judy Haley, president of Texans for the Advancement of Medical Research.

Kathy Miller, president of the Texas Freedom Network, called the vote's timing a "sneak attack."

"It's a shameful case of putting politics ahead of science as well as patients and their families," she said.

The bill, HB 225 by Ken Paxton (R - District 70, McKinney)reads as follows:

By: Paxton, Olivo, Christian, Chisum, Parker, H.B. No. 225 et al.

A BILL TO BE ENTITLED AN ACT
relating to prohibiting the use of state money for certain
biomedical research.
BE IT ENACTED BY THE LEGISLATURE OF THE STATE OF TEXAS:
SECTION 1. Subtitle H, Title 2, Health and Safety Code, is amended by adding Chapter 169 to read as follows:

CHAPTER 169. BIOMEDICAL RESEARCH
Sec. 169.001. PROHIBITION ON USE OF STATE MONEY FOR CERTAIN BIOMEDICAL RESEARCH. A person may not use state money for biomedical research if federal law prohibits the use of federal money for that research on January 1, 2007.
SECTION 2. This Act takes effect September 1, 2007.

For those of us who object to embryonic stem cell research, the bill serves the purpose of preventing our tax dollars from being used to destroy embryos whether from existing in vitro embryos or from purposeful creation of new embryos for the purpose of research, including cloning or parthenogenesis.

And for the fiscally responsible, the bill ensures that any research we pay for will be eligible for additional Federal research funds, and/or we won't spend money on redundant labs and equipment.

The House was in session until nearly midnight last Thursday, and began hearing testimony on HB 225 about 1 AM. They were in session, hearing about stem cells and cloning, until 5:30. (I had to work on Friday, so I went home at 1, and didn't get to testify.) The Committee met again on Friday: for a few minutes at 8 AM and again after the House adjourned for the day. The Chair, Representative David Swinford (R- 87th District, Amarillo), was a little punch drunk from being up all night - the maximum amount of sleep he could have gotten if he'd stayed at the Capitol would have been about 2 hours.

Representative Swinford made an effort to make sure that the members were present, and all were at certain points. However, the Committee members came and went both Thursday night and Friday. In fact, Representative Farrar (D-148, Houston) didn't attend Thursday's meeting at all, and Chairman Swinford reminded her on Friday that she probably wanted to "vote against this bill."

It's possible to watch both Committee meetings on line.

The Best Misdirection on Stem Cell Research

This guy deserves some sort of note/notoriety:

From the "News" section of the online Worcestershire (Massachusetts) Telegram & Gazette:

Apr 12, 2007

Stem-cell reversal

Scrap Romney restrictions on legitimate research


Gov. Deval L. Patrick’s effort to reverse restrictions on stem-cell research imposed by his predecessor is most welcome.

The restrictions, adopted by the state Public Health Council, are in direct opposition to 2005 legislation, enacted over former Gov. Mitt Romney’s veto, that permits human embryonic stem-cell research in the state. The former governor was opposed to the provision in the law that allowed for “somatic cell nuclear transfer.” The technique gives researchers a new way to study the development of a particular disease because the stem cells are created from the DNA of patients who suffer from that disease. Just this week, researchers reported that 13 young diabetics in Brazil being treated with their own stem cells are living insulin-free, some for as long as three years.

Make no mistake: Exacting and consistent guidelines must apply to research using stem cells. Human cloning already is banned in Massachusetts, a prohibition enforced by strong criminal and civil penalties. The law passed in 2005 also limits to two weeks of development the time during which embryonic stem cells could be harvested for research or treatment of patients. (Emphasis mine)

First this is an editorial, not news.

Second, Human cloning is not banned in Massachusetts. There is an attempt to redefine cloning as implanting a cloned human embryo, and a mandate to kill those clones by the time they are 14 days old.

However, the greatest fraud is the last sentence of the first paragraph: plopping a report of adult stem cell success into a story about embryonic stem cells, as though the latter were a ". . . a new way to study the development of a particular disease because the stem cells are created from the DNA of patients who suffer from that disease."

Juvenile Diabetes Adult Stem Cell Cure?

The Journal of the American Medical Association has published a study - free online here - that describes successful treatment of 13 patients with their own stem cells. Some of the patients have been able to go without insulin or any other medications to control their diabetes.

15 patients with new onset "Juvenile Onset," "Insulin Dependent," or Type I diabetes received shots to stimulate production of their own bone marrow stem cells. Those cells were collected by "leukapheresis," a process where the blood is filtered to remove specific cells.

The bone marrow was killed and the patients received anti-thymocite antibodies to wipe out more of the white blood cells (from the thymus that might not be in the bone marrow.

Then, the patients received their own bone marrow stem cells.

During a 7- to 36-month follow-up (mean 18.8), 14 patients became insulin free
(1 for 35 months, 4 for at least 21 months, 7 for at least 6 months; and 2 with late response were insulin-free for 1 and 5 months, respectively).

Just as Dr. John Willerson of the University of Texas Health Science Center at Houston did a few years ago to explore the use of adult stem cells in the treatment of heart disease, Dr. Richard Burt of Northwestern University in Chicago went down to Brazil in order to perform the research. It was easier to receive permission from the local ethics board to use stem cell transplants - actually, an autologous bone marrow transplant.

The news reporters and some bloggers are criticizing the research for a lack of controls as well as the use of teen subjects.

Tell me - if your son or daughter were diagnosed tomorrow with insulin dependent diabetes, would you look into a plane trip to Brazil?

Embryos and cloning on Senate agenda this week

Opponents argue that the research is unethical, because deriving the stem cells destroys the blastocyst, an unimplanted human embryo at the sixth to eighth day of development.

Michael Sandel, Ph.D. )philosopher)in the April 4, 2007 Boston Globe

WASHINGTON (Reuters) - Stem cells will be at the top of the agenda for the U.S. Senate when it returns on Tuesday with supporters of the research hoping they can change the president's mind on the issue and opponents hoping to have a say about their stand.

. . ."We got a super-majority under the Republican-controlled 109th Congress," said Sean Tipton of the American Society of Reproductive Medicine, which lobbies in support of embryonic stem-cell research.

Tipton said the current Democratic-controlled Senate will be even friendlier. "When the Senate passes this bill, the president is going to be under incredible pressure to acknowledge that the science has changed and to acknowledge that the American people support this research," he said in a telephone interview.

Washington Post April 8, 2004

"The bill is a Trojan Horse. It contains language directing the Secretary of HHS "to conduct and support basic and applied research having pluripotent potential" so long as "That the isolation, derivation, production, or testing of such cells will not involve-(1) the creation of a human embryo or embryos for research purposes"

SCNT involves just such technique. The clear implication is that under this language SCNT is "unethical." Passage of this bill would make the day for NIH funding of SCNT difficult or impossible."

Bernie Seigel, lawyer (the one who sued the Raelians for custody of their children) on Stem Cell Information blog


We will hear much about how "science has changed" since people really really want cloning and stem cell research this week.

We'll hear that it's all morals and wrong-headed religion.

We'll hear that we're killing people by opposing SCNT and embryonic stem cell research.

We probably won't hear a lot about the heart repair news, the man who's Parkinson's is improving after a trip to Asia, or all the people who receive bone marrow and umbilical cord blood cells this week.

We probably won't hear much about Dr. Atala's cells from the placenta. Or the embryonic-like stem cells from umbilical cord.



Call your Senators every day this week!

The Nonsense of the Market for Eggs -

The New England Journal of Medicine has a free text and audio interview on the subject of women who donate/sell/give their oocytes or eggs for other women to become pregnant through in vitro fertilization (IVF) or for scientific research.

"Perspective: The Egg Trade — Making Sense of the Market for Human Oocytes" by Debora Spar (Free Full Text)

Audio interview with Debora Spar and Emily Galpern


Listening to the debate, the controversy - or the effort to discover and maintain a controversy - seems a bit strained. Elitist white women who are "pro-choice" when it comes to abortion of embryonic and fetal humans, and who say they do not object to embryonic stem cell research, itself - who wouldn't mind how many embryonic humans die as long as no adult woman is exploited - speaking of poor black women's right or risk in egg donation reminds me of a bioethics afternoon TV talk show.

If the right not to be created and killed is dependent on "choice," then so is the right not to be exploited or even enslaved. If compassion for already born children and adults is really important, then why not use fetal stem cells (as has been proposed in nerve regeneration studies, the 8 week "embryos" were actually fetuses that had been aborted), paying women to abort or telling women that their babies died at birth in order to harvest the baby's embryonic stem cells (as has been done in the Ukraine), or harvesting the organs of prisoners, whether on death row or not (China and, possibly in South Carolina).

What is not mentioned in this article is the other hazard in the "sharing" of oocytes with other women or with researchers in return for a discount on her own in vitro fertilization costs. In the body, the oocyte only lives about a day after ovulation.

The fact is that the best chance for fertilization and in the limited success that has come with making human embryos with SCNT (those few that begin to divide at all) comes when the egg is used only an hour after it's removed from the body.

Therefore, any woman who "shares" her eggs with researchers will not have a chance to know whether or not any of the oocytes she did not "share" - the ones the technicians kept for fertilization for her - were actually fertilized, much less whether she was able to get pregnant herself.

Liver cell regeneration and adult stem cells

Wesley Smith posted to his own blog and to Bioethics.com about the research out of Germany showing that patients' own bone marrow stem cells can be stimulated to regenerate (normal) liver stem cells and then liver tissue, allowing the regrowth of enough new liver that surgeons can remove the cancer. (UK Telegraph article here, the abstract at Radiology online here.)

The next day, we learned that White House Press spokesman, Tony Snow, has metastatic colon cancer in his liver. This post was prompted by a not-so-nice comment on one of the non-prolife, pro-embryonic-stem-cell-research blogs that we should promote embryonic stem cell research. There's a much kinder and informative post at the Cheerful Oncologist.

Mr. Snow's illness may help educate and save many lives, both embryonic and non-embryonic.

I hope that the hope of stem cell research will be spread including the good news that multiple studies concerning the fine-tuning of knowledge about the precise population of stem cells that are functioning to regenerate the liver, and I believe that there will soon be treatments using adult, but not embryonic stem cell treatements. The patients' own stem cells will be much easier to get past any Ethics Committee than any embryonic stem cells.

For more information try a "Pub Med" search on "liver regeneration." at "Entrez Pub Med." There are 20 or so promising articles on non-embryonic stem cell liver regeneration in the last month, including this one from the authoritative journal, Stem Cells, that appears to have identified the specific population of cells from the liver that serve to become liver stem cells and then functioning liver.

Texas Politics, Bias and Bioethics

"All politics is local," is a quote attributed to - and the title of a book co-authored by - the late, former Speaker of the House, Tip O'Neill.

The lesson seems to be one that Texas State Representative Juan Garcia, D-Corpus Christi, learned well. It doesn't hurt to stack the deck in your favor, either.

Evidently, the Representative held a meeting at a church in Corpus Christi, Texas and only invited the people that agreed with him to present arguments on stem cell research to a local group of clergy.

Read "stem cell research" to include embryonic stem cells from human embryos.

I'm certain that the Representative knows the names of groups who could have directed him to people like me who could make the case for the basic science and human rights issues inherent in "the stem cell debate." (Okay, I did say, "people like me.")

Instead, the clergy evidently found themselves faced with advocates who do not believe that research in stem cells and regenerative, cellular medicine can proceed without embryonic stem cells. Advocates who include representatives from State Universities and from the "Texans for the Advancement of Medical Research," a group dedicated to the advancement of destructive embryonic stem cell research and cloning.

A similar one-sided, and self-serving argument was made this week by Tom Okarma, the president of Geron, one of the biotech companies that holds the patents on human embryonic stem cells.

This, in spite of proof such as that given to the House State Affairs Committee last Monday, of children who are alive because of stem cell transplants from cord blood. And the hope of so much more from readily available umbilical cord cells: including functional liver tissue, lung cells, nerve cells and pancreatic islet cells.

Umbilical Cord Blood Saves Lives

Today, the Texas House State Affairs Committee heard from a young man who was born with sickle cell disease. Young Joseph, Jr. told the Representatives that his baby brother saved his life. And now, he doesn't have to take medicine or get shots any more. (The oblivious hero slept through the hearing.)

And of course, I told about my granddaughter who received cord blood stem cells at 15 months old from an unrelated, anonymous little boy to cure her Kostmann's nutripenia. That's her with me, last August when we testified to the Senate State Affairs Committee.

You can watch the video at the Texas Legislature Online website archived files from 3/12/07, here, beginning around 25 minutes in. (Don't miss the earlier testimony in favor of legislation to protect embryos and embryo adoption. Joseph and his family testify at 45 to 47 minutes.)

Representative Robert Puente (D- 119) presented his House Bill 709 was before the Committee and is a perfect example of the "common ground" that is possible for those of us looking for ethical ways to further (ethical, non-embryonic) stem cell research.

The Bill would require the State Department of Health Services to develop and distribute a brochure to educate expectant parents about donating and banking cord blood. We heard that there are free opportunities for all mothers and fathers to donate their child's cord blood, if they have time to make the arrangements.

We also were privileged to hear from David Harris, Ph.D., of The University of Arizona. (His testimony begins at 30 minutes on that video) Dr. Davis began the first cord blood bank, and he told us that his children were the first to have their cord blood banked at birth.

I learned quite a bit, including that there are out of State public banks that will accept cord blood stem cells from Texas, and that there is a procedure to donate blood from a private, "family" bank to the public bank.


Here's a few sites with more information:

The Texas Cord Blood Bank

The MD Anderson Cord Blood Bank

HealthBanks (a commercial health information site)

Truly transplantable lung stem cells

Researchers at The University of Michigan have proven that mesenchymal stem cells are present in the lungs, and that these cells have transplanted along with the rest of the lung.

In the past, it was believed that the mesenchymal stem cells ( a versatile group of stem cells - see the information in the quote below) were derived from the patient's lungs. We now know that they came from the donor and they they persist for years, aiding in the repair and function of the

In the cases where the donor and recipient are different genders, most of the stem cells are found to be from the donor. Some of the cells have been found more than 11 years after the transplant.

So much for the "first transplantable" claims out of Houston.

One of the most telling findings was that, in cases where the transplant donor and recipient were not of the same sex, nearly all the MSCs (about 97 percent) originated in the donor, indicating that they were present in the tissue since the time of transplantation. "We were able to isolate the cells derived from the donor as far as 11,5 years after transplantation," says Lama, assistant professor in the Division of Pulmonary and Critical Care Medicine at the U-M Medical School. "We discovered the existence of a population of MSCs that reside and self-renew in the tissues of the adult lung – something that might hold true for other organ systems as well.

"Potentially the most important outcome of our finding is that it could lead to an understanding about therapeutic options using MSCs that reside in adult organs," Lama continues. "These lung-derived cells are different from MSCs derived from bone marrow in the expression of various genes, which makes us believe that they are specific to the organ they are isolated from."

The study appears online March 8 in advance of publication in the April print issue of the Journal of Clinical Investigation.

MSCs are widely seen as a potential source of therapies for numerous diseases and conditions, such as heart disease, cystic fibrosis, graft-versus-host disease, muscular dystrophy, and as a possible source for improved recovery of cancer patients undergoing chemotherapy.

Lama’s laboratory currently is working on another study involving the lung-derived MSCs that shows potential importance of these cells in lung transplantation. That study is not yet complete, but so far it indicates a very strong ability of these MSCs to suppress the immune cells that are involved in organ rejection. In addition to helping prevent organ rejection, other possible uses for the lung-derived MSCs could be therapies related to heart attack and pulmonary fibrosis, Lama says.

MSCs are termed progenitor cells; that is, they can differentiate into only limited number of cell types such as bone, cartilage and fat cells. However, previous laboratory studies have demonstrated the beneficial effect of these cells in various diseases, such as models of heart attacks and pulmonary fibrosis.

The current study of MSCs included 172 bronchoalveolar lavage fluid samples collected and analyzed from 76 lung transplant recipients at the U-M Health System. The ability to isolate these cells with relative ease from lavage fluid is a very significant finding as it provides a potential source to isolate MSCs, says Victor J. Thannickal, M.D., associate professor of Internal Medicine in the Division of Pulmonary and Critical Care Medicine and senior author on this study. "The specific roles of these cells in chronic lung diseases are yet to be fully defined, but will be an active area of research in years to come." Source : University of Michigan Health System

Umbilical Cord vs. Embryonic Stem Cells

The Proceedings of the National Academies of Science (PNAS) has published the article that was the subject of this blog last week, and which claims that researchers at the University of Texas at Houston have produced the "first transplantable source of lung epithelial cells." There is no evidence that these cells are "transplantable," and they are definitely not the first team to produce Alveolar Type II ("ATII") lung cells from more primitive stem cells. The article does an excellent, if technical, job of explaining the importance of ATII lung epithelial cells:

The alveolar epithelium covers [approximately] 99%of the internal surface area of the lung and is composed of two major cell types, the alveolar type I (ATI) cell and the alveolar type II (ATII) cell. ATI cells are large flat cells through which exchange of CO2/O2 takes place. They cover [approximately] 95% 0f the alveolar surface and comprise [approximately] 40% of the alveolar epithelium and 8% of the peripheral lung cells. In contrast, ATII cells are small, cuboidal cells that cover [approximately] 5% of the alveolar surface and comprise 60% of the alveolar epithelium and 15% of the peripheral lung cells. They are characterized by the unique ability to synthesize and secrete surfactant protein C (SPC) and by the distinct morphological appearance of inclusion bodies, known as lamellar bodies. Important functions of ATII cells are (i) to synthesize, store, and secrete surfactant, which reduces surface tension, preventing collapse of the alveolus; (ii) to transport ions from the alveolar fluid into the interstitium, thereby minimizing alveolar fluid and maximizing gas exchange; (iii) to serve as progenitor cells for ATI cells, which is particularly important during reepithelialization of the alveolus after lung injury; and (iv) to provide pulmonary host defense by synthesizing and secreting several complement proteins including C3 and C5 (1–3) as well as numerous cytokines and interleukins that modulate lymphocyte, macrophage, and neutrophil functions (4). Severe pulmonary diseases can be caused by deficiencies or genetic mutations in proteins synthesized by ATII cells that are important in maintaining normal lung homeostasis. For example, complete deficiency of surfactant protein B (SPB) is caused by genetic mutations in the SPB gene. This deficiency results in impaired pulmonary surfactant composition and function and is a major cause of fatal neonatal respiratory disease (5, 6). In addition, ATII cells synthesize and secrete the serine protease inhibitor alpha-1-antitrypsin (alpha-1 AT) which also plays a key role in alveolar homeostasis by regulating protease imbalance and adjusting fluid clearance (7, 8), the importance of which is supported by the association of alpha-1 AT deficiency with the development of pulmonary emphysema (9). Cystic fibrosis is thought to be primarily a disease of the upper airway and submucosal epithelia and is caused by mutations in the cystic fibrosis transmembrane conductance receptor (CFTR) (10). CFTR is an important regulator of Cl and liquid transport in the lung (11–14) and is functionally expressed by human ATII cells, strongly suggesting a critical role for CFTR in regulating ion and fluid transport in the lung alveolus in addition to the upper airway (13).

(The numbers in parentheses refer to footnotes. Also, I had to change some of the characters to words: "alpha" and "approximately")

The PNAS report and UT Houston's Press Release do not contain any note about the earlier umbilical cord blood stem cell research, although the latter was published on line and in print in Cytology, at least 2 weeks before the initial submission of the PNAS article.

Both research teams report that they followed the techniques developed and reported in the lab of another researcher, Samadikuchaksaraei, in growing, multiplying and guiding the differentiation of their primitive cells toward the more specialized lung cells that were desired. Both report the successful production of ATII lung cells, as demonstrated by the way the cells look and by demonstrating the production of Surfactant Protein C - which, in human development is only found in mature ATII cells after the unborn (or premature) child has reached 36 weeks of gestation.

The Houston team claims that one reason their process is superior to the earlier Embryonic Stem Cell research is that they were able to produce mature cells in 10 days, while Samadikuchaksaraei's team took 15 days. If the ability to produce the cells in what Wetsel, et. al., describe as a "timely manner," then it is important to note that the Minnesota team produced their mature ATII cells in 3 to 8 days.

The Houston team also claims that is possible that their new cell lines might one day be transplanted, although there has never been any research reporting the successful transplantation of epithelial cells into the lungs. Another problem is that the cells were guided to change by "transfection" with a segment of DNA that is inserted into the genes of the cells, using a retrovirus. Any use of these cells, even if anyone ever proves that we can transplant cells into the lung and cure a disease, will be complicated by years of research to prove that the gene therapy that produced these cells is safe and stable in the lungs of the patients. The authors do not give us any references to support this hypothesis.

From the Discussion section of the PNAS article:

"Lung injury due to chronic pulmonary diseases, such as chronic
obstructive pulmonary disease and asthma, and inherited genetic disorders, such as cystic fibrosis and
1-AT deficiency are leading causes of morbidity and mortality worldwide. Cystic
fibrosis and
1-AT deficiency are two of the most common inherited genetic defects affecting Caucasians. In addition, SPB deficiency is a major cause of respiratory disease and fatality in neonates. All three of these diseases are caused by single-gene defects and therefore have been logical candidates for gene therapy. However, efficient vector delivery and sufficient transgene expression needed for therapeutic benefit have remained elusive. Recent research advances indicate that gene delivery via transplantation of cells derived from human stem cells may provide an attractive alternative to viral or liposome vector based gene therapies. Moreover, transplantation of cells derived from human stem cells may prove ideal for the repair and regeneration of injured lung tissue.

Because of its ability to proliferate as well as to differentiate into ATI cells, the ATII cell is an excellent choice of lung cell for possible therapeutic use in gene delivery and repair of the alveolus.

. . . The use of ES cells as a source of transplantable cells in the lung alveolus will require the generation of significant quantities of highly pure ATII cells. To achieve this goal, we chose to genetically modify hES cells so that resulting differentiated ATII cells could be enriched through antibiotic selection. Our approach was to establish a stable transfected hES cell line containing a single copy of the human SPC promoter-Neor fusion gene. When subjected to differentiation in vitro, it was hypothesized that ATII cells derived from this genetically modified hES cell line (SPCP/NEO.74) would express the Neor gene and would therefore survive G418 antibiotic selection, whereas, all of the other differentiated cell lineages as well as the pluripotent cells would be eliminated by G418 selection. Immunocytochemical and flow cytometric analysis of the surviving G418-selected cells supported this hypothesis, indicating that this genetic selection approach resulted in an enrichment of hES-ATII cells to 99% when cultured on Matrigel-coated plates. Our protocol reproducibly produced from each 10-cm culture dish 106 essentially pure ATII cells within 15 days of differentiation. These differentiated ATII cells survive for at least 2 days in culture in the absence of G418 and will provide in a timely manner sufficient numbers of pure ATII cells for future transplantation investigations."

(No footnote references were removed from this quoted portion.)


The abstracts are available on line for free, but the actual articles are available only by subscription or by paying for temporary access:

From Proceedings of the National Academies of Science, published online March 2, 2007

"A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells"

Dachun Wang, David L. Haviland, Alan R. Burns, Eva Zsigmond, and Rick A. Wetsel. Research Center for Immunology and Autoimmune Diseases and Laboratory for Developmental Biology, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center; Department of Biochemistry and Molecular Biology, University of Texas Medical School; and Cardiovascular Sciences Section, Department of Medicine, Baylor College of Medicine. Communicated by C. Thomas Caskey, University of Texas Health Science Center, Houston, TX, January 4, 2007 (received for review November 22, 2006)

Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute 60% of the pulmonary alveolar epithelium. These cells are crucial for repair of the injured alveolus by differentiating into alveolar epithelial type I cells. ATII cells derived from human ES (hES) cells are a promising source of cells that could be used therapeutically to treat distal lung diseases. We have developed a reliable transfection and culture procedure, which facilitates, via genetic selection, the differentiation of hES cells into an essentially pure (>99%) population of ATII cells (hES-ATII). Purity, as well as biological features and morphological characteristics of normal ATII cells, was demonstrated for the hES-ATII cells, including lamellar body formation, expression of surfactant proteins A, B, and C, alpha-1-antitrypsin and the cystic fibrosis transmembrane conductance receptor, as well as the synthesis and secretion of complement proteins C3 and C5. Collectively, these data document the successful generation of a pure population of ATII cells derived from hES cells, providing a practical source of ATII cells to explore in disease models their potential in the regeneration and repair of the injured alveolus and in the therapeutic treatment of genetic diseases affecting the lung.
Keywords: complement , differentiation, surfactant proteins, alpha-1-antitrypsin, cystic fibrosis transmembrane conductance receptor

And here's the abstract of the report from November in Cytotherapy, (2006) Vol. 8, No. 5, 480-48 (Note the association with BioE, Inc., the company that's doing the cancer research with MD Anderson):

"Differentiation of umbilical cord blood-derived multilineage progenitor cells into respiratory epithelial cells."

MJ Berger, SD Adams, BM Tigges, SL Sprague, X-J Wang, DP Collins and DH McKenna, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota, USA, Clinical Cell Therapy Laboratory, University of Minnesota Medical Center, Minneapolis, Minnesota, USA, and BioE Inc., Saint Paul, Minnesota, USA

Background - Umbilical cord blood (UCB) has been examined for the presence of stem cells capable of differentiating into cell types of all three embryonic layers (i.e. endo-, ecto- and mesoderm). The few groups reporting success have typically confirmed endodermal potential using hepatic differentiation. We report differentiation of human UCB-derived multipotent stem cells, termed multilineage progenitor cells (MLPC), into respiratory epithelial cells (i.e. type II alveolar cells).
Methods - Using a cell separation medium (PrepaCyte-MLPC; BioE Inc.) and plastic adherence, MLPC were isolated from four of 16 UCB units (American Red Cross) and expanded. Cultures were grown to 80% confluence in mesenchymal stromal cell growth medium (MSCGM; Cambrex BioScience) prior to addition of small airway growth medium (SAGM; Cambrex BioScience), an airway maintenance medium. Following a 3 - 8 day culture, cells were characterized by light microscopy, transmission electron microscopy, immunofluorescence and reverse transcriptase (RT)-PCR.
Results - MLPC were successfully differentiated into type II alveolar cells (four of four mixed lines; two of two clonal lines). Differentiated cells were characterized by epithelioid morphology with lamellar bodies. Both immunofluorescence and RT-PCR confirmed the presence of surfactant protein C, a protein highly specific for type II cells.
Discussion - MLPC were isolated, expanded and then differentiated into respiratory epithelial cells using an off-the-shelf medium designed for maintenance of fully differentiated respiratory epithelial cells. To the best of our knowledge, this is the first time human non-embryonic multipotent stem cells have been differentiated into type II alveolar cells. Further studies to evaluate the possibilities for both research and therapeutic applications are necessary.
Keywords - endodermal differentiation, respiratory epithelium, stem cells, umbilical cord blood.

Embryonic SC researchers claim doubtful "first"

Beware of Press Release science reporting - the job of the news release or public affairs department of an institution is to get publicity, not to promote scientific knowledge. There's no peer review until after the fact, and the goal is to catch our attention, rather to educate.

A case in point was the announcement yesterday from the the University of Texas at Houston Brown Foundation's Institute of Molecular Medicine researchers' Press Release that begins:

UT Scientists Develop Promising New Procedure To Differentiate Human Embryonic Stem Cells

HOUSTON – (Feb. 26, 2007)—Molecular scientists at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) – which is part of the University of Texas Health Science Center at Houston – have developed a new procedure for the differentiation of human embryonic stem cells, with which they have created the first transplantable source of lung epithelial cells.

The process, created in the laboratory of Rick A. Wetsel, Ph.D., a professor of molecular medicine at the IMM, is described in this week’s edition of the Proceedings of the National Academy of Sciences (PNAS). Research scientist Dachun Wang, M.D., is lead author of the article, “A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells.”

“We have developed a reliable molecular procedure which facilitates, via genetic selection, the differentiation of human embryonic stem cells into an essentially pure population of lung epithelial cells,” said Wetsel, noting the procedure also can be used to create other types of highly-specialized cells.

The word that seems to carry the most weight in that first paragraph is "transplantable." And a lot depends on how they define that word.

Since I can't find any mention of the article on the internet, except in the press releases, I'm not sure exactly what "transplantable" cells means to these guys.

However, I am convinced that they are not the only ones to derive alveolar II lung epithelial cells from stem cells.

As reported, here and very few other places, last November 1, 2006 - you know, just before the Midterm election and Missouri's disaster with the clone and kill bill - researchers at the University of Minnesota Medical School at Minneapolis published a report in Cytotherapy on their production of functioning alveolar II epithelial lung cells, capable of producing surfactant, from a certain population of umbilical cord blood stem cells:

BackgroundUmbilical cord blood (UCB) has been examined for the presence of stem cells capable of differentiating into cell types of all three embryonic layers (i.e. endo-, ecto- and mesoderm). The few groups reporting success have typically confirmed endodermal potential using hepatic differentiation. We report differentiation of human UCB-derived multipotent stem cells, termed multilineage progenitor cells (MLPC),into respiratory epithelial cells (i.e. type II alveolar cells).
Methods Using a cell separation medium (PrepaCyte-MLPC; BioE Inc.) and plastic adherence, MLPC were isolated from four of 16 UCB units (American Red Cross) and expanded. Cultures were grown to 80% confluence in mesenchymal stromal cell growth medium (MSCGM; Cambrex BioScience) prior to addition of small airway growth medium (SAGM; Cambrex BioScience), an airway maintenance medium. Following a 3-8-day culture, cells were characterized by lightt microscopy, transmission electron microscopy, immunofluorescence and reverse transcriptase (RT)-PCR.
Results MLPC were successfully differentiated into type II alveolar cells (four of four mixed lines; two of two clonal lines). Differentiated cells were characterized by epithelioid morphology with lamellar bodies. Both immunofluorescence and RT-PCR confirmed the presence of surfactant protein C, a protein highly specific for type II cells.
Discussion MLPC were isolated, expanded and then differentiated into respiratory epithelial cells using an off-the-shelf medium designed for maintenance of fully differentiated respiratory epithelial cells. To the best of our knowledge, this is the first time human non-embryonic multipotent stem cells have been differentiated into type II alveolar cells. Further studies to evaluate the possibilities for both research and therapeutic applications are necessary.

Unfortunately, most of the sites that are picking up the PR are just publishing it whole, without evaluation or editing.

For instance, ScienceDaily, one of my favorite science news sites, published the intact, clearly labeled "Press Release", although that site also published the press release on the earlier, UCB stem cell derivation of alveolar II cells.

So far, I've only seen one note on the UT announcement that distills the info available to the news, without the hype. LongevityMeme, a blog devoted to technology and science showing promise for the extension of the human lifespan, has not duplicated the silly "transplantable" or "first" claims. The post explains the pertinent points very well (click to the original for the embedded links):

Examples of continually improving control over stem cells have been rolling in of late; here is one from the University of Texas: "We have developed a reliable molecular procedure which facilitates, via genetic selection, the differentiation of human embryonic stem cells into an essentially pure population of lung epithelial cells ... the procedure also can be used to create other types of highly-specialized cells. ... The method involves the use of protein markers under the control of cell-specific promoters to convert undifferentiated human embryonic stem cells into highly-specialized cells. The human embryonic stem cells were cultured on specially coated dishes and transfected with a lung epithelial gene regulator of a drug selection gene. ... It is a general technology for developing select cells from human embryonic stem cells. The technology has allowed us to develop a platform that could potentially be useful in the development of spinal cord cells, heart cells, nerve cells and others. ... transplantable alveolar epithelial type II cells can be explored as treatments for pulmonary genetic diseases, acquired lung disease, as well as lung trauma caused by car accidents, gunshot wounds and sports injuries. ... These are the cells that can potentially be used for regenerative lung repair."

(emphasis is mine)

The "transfected gene" treatment used to induce the embryonic stem cells to develop along the desired line appears to me to be a step that will complicate the testing and approval of the use of these cells in humans. I'm not convinced that surgery will be the optimum use of the outcome of stem cell regenerative medicine. I'm convinced that we will use what we learn to induce, stimulate and and recruit the body's own regenerative stem cells in place, as we need them

If the transfected gene is safe, then, perhaps it will be the treatment in the future. Or, perhaps the UT lab and the UM lab can collaborate on truly transplantable cells, if necessary.

MIT adult stem cell research soap opera?

Yesterday's Massachusetts Institute of Technology press release ("MIT bioengineer advances survival, promise of adult stem cells")led to the story behind the story and and maybe more.

Behind them all, of course is the truth that human embryos are, indeed human, and that there is not any difference between the embryo in the petri dish and the one that each of us once was.

The February 27, 2007 Press Release concerns an article published on line in the January 18, 2007 online edition of Stem Cell Express Online. The Abstract is available here. According to the website, the paper, "Tethered EGF Provides a Survival Advantage to Mesenchymal Stem Cells" was submitted last year, on May 26, 2006 and accepted for publication January 9, 2007. The research supports that stem cells develop in reaction to and influenced by their environment and details a way to manipulate the growth factor EGF on an implanted scaffolding to encourage bone marrow mesenchymal cells to develop bone and encourage healing after surgery or severe wounds.

Linda G. Griffith, Ph. D., leads the Griffith Lab at MIT, which focuses on bioengineered tissue, using adult stem cells. In fact, the MIT press release and the Science Daily adaptation both mention that Dr. Griffith has a personal interest in preferring to avoid research on embryonic stem cells.

Griffith, who does not work with human embryonic stem cells, believes that adult stem cells offer promising therapeutic possibilities.

"I'm very optimistic about the potential for adult stem cells to be useful clinically for the problems I work on, since there are already some clinical successes based on these cells" she said. "Continuing, careful, methodical work will lead to improved therapies based on adult stem cells. We are aiming to expand the range of therapies that work in the clinic." Griffith is one of several MIT biological engineering faculty members who work with adult stem cells but not human embryonic stem cells.

Griffith is also one among many scientists around the world who have at least some objections to creation of human embryonic stem cells, for a variety of reasons. She says her current focus on adult stem cells is driven largely by the interesting science and the feasibility for near-term clinical use for the types of cells she investigates. However, she also avoids research with human embryonic stem cells following a personal experience with in vitro fertilization almost 10 years ago.

"Like some other scientists I know, my personal views about creating human ES cell lines changed when confronted with the reality of doing so from my own embryos. After this experience, I was not comfortable conducting human ES cell research myself, and I have a better understanding of why some scientists object to all work with human ES cells," she said. She also said she feels her personal views, and those of others, are respected in the scientific community.

Currently, federally funded research is only allowed on certain established lines of embryonic stem cells, although a few states, including California and Connecticut, offer state funding for broader embryonic stem cell research. There are no legal restrictions on funding to study adult stem cells.

These quotes are exactly what so many of us have been saying all along. I certainly intend to use them in any testimony I give in the future, although I wish there were not quite so much stress on the theme of "personal views." I don't see much room for personal views in whether or not the embryos who are her children and those who other researchers would disaggregate for stem cells.

What's the story behind the story? We may never know all of it. But here's just a bit from an article on the MIT website about the hunger strike of Dr. James Sherley which was also covered here earlier this month:

Additionally, Sherley also outlined his main reasons for complaint, which included denial of independent lab space by then Provost Robert Brown and the conflict of interest that resulted from the spousal relationship between Lauffenburger and BE Professor Linda G. Griffith led him to believe his case for tenure was not handled fairly.

Do not look behind the curtain! (again, with the magic tricks)

I'd say the man who said this needs both a heart and a brain:

"Ultimately, human hearts, human brains, and human kidneys and human pancreas will be re-created in their entirety from human embryonic stem cells or some combination of adult and embryonic stem cells," Willerson said.

He's certainly got enough nerve.

Tell me what happens when you get a new brain, in its "entirety," Doctor.

On the other hand, there's this brilliant man who's using the brain and heart he's got:

Dr. Karel Dicke, an oncologist at the Arlington Cancer Center, uses stem cells found in patients' bone marrow to ease their recovery from high-dose chemotherapy.

Dicke, who has conducted research into adult stem cells for more than 40 years, said he opposes the use of public funds for embryonic stem-cell research because it doesn't have enough public support. He echoed statements from opponents of such research in noting that the field may not be as promising as some have predicted.

"It is not that far along yet," Dicke said. "Scientists are making political statements."

Of course, it's really all about the money. As I've said before - stem cell therapy of the future will not depend on the destruction of embryos. The goal will be to use the patients' own stem cells in site, when and where they are needed. Umbilical cord and placental cells are plentiful and have shown themselves plastic enough to provide the tissues and organs that we will need. (Where the repair cannot be made in situ. Edited, March 19, 2007. BBN)

Researchers in Minnesota have produced beating heart muscle from stem cells taken from the hearts of rats. In humans, they say they are using muscle from the legs to heal hearts in place.

Have a look at more stem cell advances in this article.

Dr. Anthony Atala's group at Wake Forest University grew nerve stem cells that homed in to the areas of the brain where they were needed. Last year, Zurich researchers reported work to develop heart valves for babies from their amniotic stem cells, even before they were born.

We don't need the smoke and mirrors, Doctor Willerson. You and others have already shown us that we already have a future without embryonic stem cells.

Jesus, embryos, research, and IVF protesters

Newsday printed an op ed by Michael D. Kerlin, "Where faith and stem cells meet: Jesus might have us use embryos - otherwise destined to be discarded - to aid the sick and dying." (That's pretty much it, except to testify to his Christianity, his alma mater, and to lay the fate of all sick and dying at the feet of President George Bush.)

As I commented at the site, Jesus taught that "self" belongs in front of "sacrifice."

The other posters and Mr. Kerlin do not seem aware of the facts about the numbers of embryos that would actually be available for research.

And a couple of the posters are horrified that I set the responsibility for ensuring the safety of the embryonic humans on the parents and the labs who created humans in harm's way. They ask whether I would forbid in vitro fertilization (IVF) and tell men and women who are unable to have children by natural intercourse, "tough luck." One poster doubts my sincerity, since there are so few picketers and protesters outside of IVF facilities. He questions whether the protests are only hypocritical abuse and harassment of poor single women, rather than rich couples seeking IVF.

There was a RAND study on the numbers of embryos available for research (Hoffman DI, Zellman GL, Fair CC, Mayer JF, Zeitz, JG, Gibbons WE, and Turner TG. May 2003. "Cryopreserved Embryos in the United States and Their Availability for Research." Fertility and Sterility 79 (5): 1063–1069.)and Art Caplan published one a few years ago, and he was surprised at how few parents would even consider research and how reluctant they and the clinics were to simply destroy the "excess" embryos. In addition, for those currently frozen, it's unlikely that the proper informed consent.

Yes, there are few protesters at IVF clinics, because most people have empathy for the parents who want children so much that they would go through all that IVF requires. Also, most people simply aren't aware of how many embryos are discarded.

However two wrongs don't make a right. Again, "self" should always precede "sacrifice."

It was our empathy that created the current situation, where the brothers and sisters of those babies who are now in the arms of the parents who wanted them so much died during the IVF process and more are frozen and at risk. We must steel ourselves to resist the temptation to help "the sick and dying," everyone from celebrities to tiny children who beg us and our legislators to sacrifice human embryos for their sake.

Who is to decide that some humans may be destroyed and dissected for research or so many spare parts for the benefit of someone else?

Because we know that embryonic stem cell research leads to a slippery slope. We know because some men and women have already fallen down that slope.


I'm sure that most of us have read about the women paid to become pregnant and have abortions for research and profit in the Ukraine and about all the full term healthy babies who mysteriously die in some of that country's hospitals. At one of these hospitals, graves of infants who had had brains and other organs have been found.(More here and here. Warning - graphic descriptions)

"Flawed" Adult Progenitor Cells Study

Lots in the stem cell news about the report a few years ago that certain populations of adult stem cells can become "any cell in the body."

No one doubts whether Verfaillie found the stem cells that she said she did. The problem is that there were mistakes in the reports about how she actually did it and that other labs have had a hard time duplicating her work. From the New Scientist article on the "flaws":

"In her most recent paper, Verfaillie and Irving Weissman, a stem cell biologist at Stanford University in California, showed that MAPCs can give rise to all the cell types found in blood, but it is still unclear whether MAPCs are as versatile as she claimed in the original Nature paper."

Many researchers are unable even to isolate them. “They’re very testy cells,” observes Amy Wagers of Harvard University, who spent a week in Verfaillie’s lab trying in vain to learn the technique.

The problems with the marker profiles may help explain these difficulties. “If I had been following this recipe since 2002, I’d be extremely angry,” says Jeanne Loring, a stem cell biologist at the Burnham Institute for Medical Research in La Jolla, California.

There's a much more detailed evaluation on the original report in yesterday's The Scientist:

Tim Mulcahy, vice president for research at the University of Minnesota, told The Scientist that the university asked two experts in flow cytometry to review the data, and they found "technical flaws with the paper," but said they didn't have the background to determine if the problems affected the results. The university then contacted three stem cell experts, and two agreed to review the data. One reviewer said the flawed data wouldn't affect the findings, and the other said the flaws might "weaken the conclusions," Mulcahy noted. He said the university decided to release the information to allow the scientific community to debate the impact of the panel's findings. The university is not releasing the names of the stem cell experts who reviewed the data.

Mulcahy added that Verfaillie asked the university to investigate the findings, and has been very helpful. "This was all done with her consensus and her willing cooperation."

The outside experts agreed with Aldhous that the antigenic markers used to define the MAPCs were in question, Verfaillie said -- "as do I," she added. But these concerns don't affect the results, she noted. "As MAPCs were - and still are - not defined on the basis of a phenotype, but based on functional criteria, I believe therefore that the conclusions of the papers are still correct. Obviously that is up to the scientific community to decide."

The current debate is over a "minor point," said Diane Krause, a stem cell researcher at Yale University. The concerns about the Nature paper focus on the "antigenic profile of these cells, and not what they can do," she told The Scientist. "I certainly believe Catherine," Krause added. "I think she's got the highest amount of integrity."

Indeed, researcher Mark Clements, from Westminster University in London, UK, has had some success replicating Verfaillie's results with human cells. "The inaccuracies in Catherine's papers do cast a shadow over her work," he told The Scientist, "but I do believe the underlying premise is valid."

Clements said the errors in the paper raise questions about the definition of MAPCs in terms of cell markers, but agreed that the overall premise of the paper is intact. "Our experience of the human cells tells us that the main problem with them is that they're so fastidious to grow," he said. This would explain why other labs and indeed Catherine's lab have had difficulties replicating this work, Clements said.

Thomas Braun from the Max Planck Institute for Heart and Lung Research in Germany told The Scientist he thinks the explanation for the duplication of the figures was adequate. "Things like that happen although it is always hard to understand why such errors are not recognized at an earlier stage," he said.

A follow up study published in Journal of Experimental Medicine (I don't have link) and reported on in Science,that included doubter Irving Weissman proved multipotency, if not pleuripotency.

"The work has impressed one skeptic, Stanford blood stem cell researcher Irving Weissman, who collaborated on the new work. Weissman calls the result "remarkable." His skepticism, he adds, "makes me a perfect collaborator, because I insisted on very rigorous criteria for the experiments."

He emphasizes, as does Verfaillie, that these cells are clearly not as versatile as ES cells. But despite their limitations, they could prove to be useful therapeutically.

"A lot of people have lost interest in MAP cells by this point," says Weissman. "What our paper will help do is get everybody to look at it again." Others agree. "I'm sure it will revive interest in MAP cells," says stem cell researcher Paul Schiller of the University of Miami, Florida."

Perhaps, now that the "recipe" is corrected, more labs will confirm the original reports.

Different populations and kinds of adult stem cells are indeed very versatile, especially for producing what we really want: stable cells that will only become the exact specialized cells that are needed, where they are needed.

Adult stem cells have yielded more populations of specific progenitor and stem cells than even embryonic stem cells. The only place that embryonic stem cells work to produce "every cell in the body" is in the original container - in the intact embryo. Elsewhere, they produce embryoid bodies or teratomas, or mutate and die out unless first manipulated to become a more specialized stem cell or progenitor cell.

Which sounds like an adult stem cell or progenitor cell, to me.

Part of the problem with all stem cell research is that, as in the press coverage, scientists have also been "shotgunning" with groups of cells as though all samples stem cells are a bunch of homogeneous one size fits all entity. Slowly but surely, we're learning what markers to look for in order to find the most primitive or the exact future lineage we need, the environment, stimulating factors and the epigenetic factors involved.

If we think the progress has been fast before, I don't think it's anything like what will happen in the next 5 years.

(HT to FreeRepublic's neverdem.)

Public Cord Blood Banks

Georgia Senator Shafer has introduced a bill that would make that State the first to dedicate funds to a public bank for both cord blood and placental and umbilical cord tissues. This follows a move across the country to begin public, rather than private, cord blood banking for therapy and research.

MD Anderson (MDA), our big cancer research and therapy center in Houston, Texas, has announced that it has received $9 million from the Federal Health Resources and Services Administration to support their Cord Blood Bank. MDA is already collecting units at two hospitals in the area.
The Texas Cord Blood Bank has been growing since a push by then Representative, now State Comptroller, Elizabeth Ames Jones and our Governor Rick Perry led the move to dedicate State funds. The first $1 million dollars in Federal money was matched by State money and again by private donations. In 2005, Governor Perry awarded a grant of an additional $1.2 million in matching funds (meaning that the grant will match each dollar donated from private donors). TCCB is currently collecting cord blood at 4 hospitals, one in North Dallas, one in San Antonio, and at hospitals in two cities in the Rio Grande Valley. (See the video on the Cord Blood Bank at Jones' campaign website.)

I'm convinced that cord tissues contain the stem cells that will offer all the therapies and hope that we hear about from the advocates of destructive embryonic stem cells. And we're throwing them away, every day.

Cow-Monkey blastocyst research

The truth about the goal of researchers seeking to make chimeras and clones is in the news, today. (A big "yuk" factor, here.)

I'm convinced that the future is in stimulating and recruiting the patient's own stem cells and regenerative potential, in site, where and when it's needed.

Animal research is acceptable, but once they start manipulating human DNA, we're dealing with humans until proven differently.

The (South) Korean Times reports on work in the lab of Koo Deog-bon:

The team, headed by Koo Deog-bon at the Korea Research Institute of Bioscience and Biotechnology, said Friday they had established a monkey blastocyst, the source of stem cells, last month via interspecies nuclear transfer.

``We started the task of infusing monkey somatic cells into cow ova, from which the nuclei had been removed, last November. After hundreds of failures, we made a blastocyst in January,'' Koo said.

``It failed to thrive. But we became sure of the potential of interspecies research _ creating a blastocyst and extracting stem cell batches from it,'' the 41-year-old senior researcher said.

A blastocyst is an embryonic form at a stage where it consists of 128 cells. With its inner cells still undifferentiated, the blastocyst is the most important source of embryonic stem cells.

Scientists have made monkey blastocysts through intra-species nuclear transfer _ implanting monkey somatic cells into enucleated monkey ova. But this is the first time that a blastocyst has been established while using non-monkey ova.

``We will generate more monkey blastocysts to achieve our goals of culturing stem cell lines with them earlier than our competitors,'' said Koo at the state-backed institute.

Developing cloned non-human primate stem cells is significant in speeding up futuristic therapy by evaluating the pre-clinical safety and immune-tolerance of stem cell transplantation.

``If we are successful, we will be able to apply the technologies to humans _ making stem cells with animal ova _ if society allows such an idea,'' Koo said.

As Koo pointed out, the interspecies experiments can in part solve some of the ethical debates surrounding the making of cloned human embryonic stem cells because they don't use human eggs.

We've heard this (stem cell) story before

Stanford scientists are working on a "stem cell treatment" to cure hearing loss due to lost nerves.

The Science Guy at the Houston Chronicle references a Wired News article, that links to the American Association for the Advancement of Science and the San Francisco Gate and an interview with Stefan Heller.

Here's a slightly better review from Medical News Today.

I believe that reading about the evolution of Heller's research will give us some indication about future treatments that result from "stem cell treatments."

Dr. Heller found stem cells in the hearing and balance systems in the ear of humans and mice.

He found that the hearing, inner-ear adult stem cells of mice don't grow and divide much after birth, but that the balance nerve cells, the vestibular hair cells are "pluripotent" ("can give rise to a variety of cell types in vitro and in vivo, including cells representative of ectodermal, endodermal and mesodermal lineages") and can be induced to form either the vestibular, balance cells or the hearing sensory cells.

Then, Heller's team discovered (free abstract, here)that human bone marrow stem cells can become progenitor cells - or the dedicated adult stem cells - that can repair damaged hearing sensory nerve cells.

[Editing note: I had the url of that abstract wrong. Also, I many have the timeline wrong, since a closer look at the abstract shows that it was only published in January, 2007.]

However, Heller and his team ignored the bone marrow cell findings and began focusing on embryonic stem cells. Why would he leave a field of inquiry that would allow each of us to have access to genetically matched cells to repair our own hearing?

Nevertheless, it turns out that the goal is to regenerate the patient's own stem cells to repair damage where it's needed in the body, when it's needed.

From the January 29, 2007 San Francisco Gate article:

On this day he is finally starting his first experiment -- growing inner ear cells in a culture dish, to test the new equipment -- and already people in the medical school are asking, "When are the first transplantations taking place?" he says. "I'm a little careful of that, because we have to do animals first."

He wouldn't be here answering this question at all if he hadn't found stem cells in the vestibular organ, which controls balance. Both balance and hearing are controlled by hair cells. When the hearing cells are damaged by illness or noise, they die off and don't come back. A University of Virginia study 15 years ago found that cells in the vestibule have shown a small and limited ability to regenerate. Heller took that further and within these cells was able to isolate stem cells that continuously multiply. In culture dishes, these regenerative balance cells can be engineered to produce hearing cells.

The logical next step would be to transplant these into the auditory canal. "The problem with any surgical approach to the ear is you have the potential of doing more damage than you can do any good," he says. "So I don't think this will be successful any time soon."

That means 10 years and 10,000 mice, maybe more of each. The immediate future is drugs.

They can be tested directly on embryonic inner ear cells to see if any lead to over-production of hair cells. If a drug could be found that stimulates enough productivity within the damaged ear, this drug could be applied to a deaf ear. These can then be tested on animals, starting in a year or so.

Texas researchers discover key to heart repair

Texas research team has published a report on the fusion of adult stem cells to damaged heart cells which enables healing of damage. In this case, the stem cells are from peripheral blood - the blood that circulates every day. Presumably, the origin of these cells is the bone marrow.

The review at Physorg.com. includes a discription of the current knowledge on heart repair and stem cells. Quoted is T.H.Yeh, M.D. one of the team from M. D. Anderson, the Texas Heart Institute at St. Luke's Episcopal Hospital and The University of Texas Health Science Center at Houston.

Because many of the drugs and therapies used to treat cancer can cause heart damage, M. D. Anderson, a world-renowned cancer therapy and research center, also invests in the study of heart disease.

Cardiac adult stem cells seem to do two different things: they divide to form blood vessels and they fuse to injured heart muscle cells or "cardiomyocytes" to cause the muscle cells to demonstrate "stemness." The original fused cells are now like very special stem cells that are cardiomyocytes that can divide and multiply for months, in order to repair the damage in the heart. Until recently, we were taught that heart muscle cells did not replicate and replace themselves in adults.

Yeh and his co-workers report on adult heart stem cells, three specific proteins, the mechanisms that stimulate their production, and evidence as to how these proteins and stem cells work after heart muscle damage. Two of the proteins, described as "sticky" similar to the two tapes in Velcro, are newly discovered by the team. Another protein, vascular endothelial growth factor or VEGF, was previously known to aid in the development of new blood vessels. In hearts, VEGF causes some of the stem cells to produce blood vessels rather than fuse to the damaged muscle cells. By a series of experiments using antibodies against the proteins in immune deficient mice with induced heart damage, the team has demonstrated one way the heart repairs itself and that the same adult stem cells can lead to new heart blood vessels and new heart muscle cells. The hope is that this discovery will allow us to increase the amount of repair in heart attack patients.

The abstract of the original article published in Circulation Research OnLine First, is available for free, here. The supplemental data and some figures are also available free, here.

The last author of the original article is James Willerson, M.D., the President of the University of Texas Health Science Center at Houston, and the man who went off to Brazil in order to do one of the first studies of bone marrow stem cells used to treat heart disease. He's been mentioned on this blog, here and here.
Unfortunately, Willerson is often quoted advocating the creation of new embryonic stem cell lines, and the destruction of more and more human embryos in order to harvest those lines.

Language change alert ("Embryonic" at 8 weeks)

We were due, I guess. We went through the redefinition of pregnancy (implanted in a uterus"), embryo (after 14 days or implanted in a uterus), cloning (therapeutic cloning, then somatic cell nuclear transplantation, nuclear transplantation, patient specific stem cells, production of "early stem cells, etc.)

And now, we're supposed to move the line of "embryonic" to eight weeks of gestation.

And we should just forget all the past promises about "14 days," implantation, along with our objections to killing the youngest of our children.

Some of us have warned that embryonic stem cell research, with it's high risk of teratomas - tumors that (to paraphrase a popular slogan) "contain all the cell lines in the body," would lead to further maturation of human embryos into the fetal stage of development. Since the goal is usable tissues and stem cells, it made sense to us that researchers will eventually get around to demanding for funding to grow the embryos in human or surrogate wombs in order to "save lives," and further their grant requests.

There have been previous examples (I'm on my way to a meeting, so the references will have to wait 'till tonight) in production of "embryonic" nerve tissues being used to treat a few children with neurological metabolic diseases. In fact, the "embryonic" tissues used to harvest these cells must come from children who are aborted at 7 to 9 weeks, technically fetuses, not embryos.

Further evidence of the possible direction of stem cell research - if we allow it - comes to us this week, from the online journal, PLOS-Medicine.

Here's the press release that showed up in my Google alerts file, from Eureka News Alerts, "Human stem cell transplants mature into neurons and make contacts in rat spinal cord.":

Human stem cell transplants mature into neurons and make contacts in rat spinal cord

Human nerve stem cells transplanted into rats' damaged spinal cords have survived, grown and in some cases connected with the rats' own spinal cord cells in a Johns Hopkins laboratory, overturning the long-held notion that spinal cords won't allow nerve repair.

A report on the experiments will be published online this week at PLoS Medicine and "establishes a new doctrine for regenerative neuroscience," says Vassilis Koliatsos, M.D., associate professor of neuropathology at Johns Hopkins. "The spinal cord, a part of the nervous system that is thought of as incapable of repairing itself, can support the development of transplanted cells," he added.

"We don't yet know whether the connections we've seen can transmit nerve signals to the degree that a rat could be made to walk again," says Koliatsos, "We're still in the proof of concept stage, but we're making progress and we're encouraged."

In their experiments, the scientists gave anesthetized rats a range of spinal cord injuries to lesion or kill motor neurons or performed sham surgeries. They varied experimental conditions to see if the presence or absence of spinal cord lesions had an effect on the survival and maturation of human stem cell grafts. Two weeks after lesion or sham surgery, they injected human neural stem cells into the left side of each rat's spinal cord.

After six months, the team found more than three times the number of human cells than they injected in the damaged cords, meaning the transplanted cells not only survived but divided at least twice to form more cells. Moreover, says Koliatsos, the cells not only grew in the area around the original injection, but also migrated over a much larger spinal cord territory.

Three months after injection, the researchers found evidence that some of the transplanted cells developed into support cells rather than nerve cells, while the majority became mature nerve cells. High-powered microscopic examination showed that these nerve cells appear to have made contacts with the rat's own spinal cord cells.

###

The research was funded by the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association and the Robert Packard Center for ALS Research at Johns Hopkins.

Authors on the paper are Jun Yan, Leyan Xu, Annie M. Welsh, Glen Hatfield and Koliatsos, all of Hopkins, and Thomas Hazel and Karl Johe of Neuralstem of Rockville, Md.

On the Web:

http://neuroscience.jhu.edu/VassilisKoliatsos.php
http://www.plosmedicine.org
http://pathology2.jhu.edu/disease/home_files/page0003.htm

There is nothing alarming - and quite a bit that's encouraging - in that press release. However, reading the actual published articles leads to the discovery that the stem cells in question come from human fetuses. I'm afraid that I don't know of any way to harvest neural stem cells from human fetuses without harming those unborn children.
Here's the first article, "Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord."

And the second, which explains where we are going:"Making Human Neurons from Stem Cells after Spinal Cord Injury"

Spinal cord cells were obtained from cervical and upper thoracic spinal cord of an eight-week-old human embryo and expanded in monolayer culture in defined medium with the mitogen FGF2 (a member of the fibroblast growth factor family).

(Emphasis mine)

In the future, perhaps fetal neural stem cells can be developed from cells harvested from placentas collected after the birth of children or as a by-product of amniotic fluid tests done for medical indications and then used as we use other cellular and tissue transplants of adult stem cells and specialized tissues.

Perhaps Dr. Atala and his research group could follow this line.

However, I expect to see a call for more money for fetal stem cell research and for a demand for an expansion of the time that human "extracorporeal" embryos can be maintained.

And won't it be interesting to see how these nascent human beings are grown to eight weeks or so?

Publish (destroy embryos) or perish

Professor James L. Sherley is losing weight on his hunger strike, but Fox News and Reuters are the only mainstream media outlets to take notice. It seems that racial discrimination, storming the Administration building of a university and even extreme measures of weight loss are not newsworthy if you're critical of embryonic stem cell research and cloning.

It doesn't matter that Dr. Sherley reported a break-through on the secret to inducing adult stem cells to divide and how and why these cells can form cancers (here and here). It is of no consequence whatever that he won an award from the NIH, and millions of dollars in research money to go with it. Unfortunately, he also criticized embryonic destruction and cloning in public, with letters to the editors in Science, Nature, and The Boston Globe.


Dr. Sherley has shown rare conscience and integrity by confronting and exposing the bias and prejudice within academia encountered by those who believe that human beings should not be killed in experiments, and most certainly should not be created for the purpose of killing.

He has been a vocal critic - albeit one who is rarely quoted in the media - of embryonic stem cell research, creating embryos for the purpose of killing for research, and of cloning in order to obtain embryos for research and killing in research.

He is using the tools - the legitimate, legal and ethical tools using current law and endangering no one other than himself - that have been provided by the law, the media and his own intellectual and moral adversaries. But, don't expect to see his story in the National news.

In the United States, the law protects those discriminated against because of their race and Dr. Sherley has charged that he is a victim of racial discrimination at the Massachusetts Institute of Technology. According to this article (from a conservative news service begun by Brent Bozell - one of the very few reporting at all on the story) points out that Dr. Sherley is "he first and only black faculty member of MIT's Division of Biological Engineering, and he was awarded a $2.5 million research grant last year from the National Institutes of Health." Colleagues support the conflict of interest demonstrated by the choice of the lead tenure reviewer - who is married to someone who was a prior critic of Dr. Sherley:
From the Boston Globe,

Some MIT professors are circulating a letter that asks for further investigation into the process that denied Sherley tenure. The letter states that a head of Sherley's department is married to a senior faculty member whose relationship with Sherley has been "openly contentious." That division head should have recused himself from deciding Sherley's case, rather than soliciting an internal letter from his wife to include in Sherley's tenure file, the letter said.

"We checked to see whether that influenced the decision, and we are confident that it did not," Clay said.

Of 740 tenured faculty members at MIT, 27 are African-American or Hispanic. Three minority faculty members have earned tenure since Sherley was denied, according to the school.

The mainstream media have not given Dr. Sherley the same publicity that they would if he would just advocate for the killing of a few embryos. Even his hunger strike is not very successful at gaining national attention.

Could it be that no one at UPI, any of the big 3 television networks, Time, Newsweek, or CNN cares about racial discrimination at MIT? There's nothing from any of these as of this morning - not one little note - according to my Google News search at about 7:30 AM CST.


Or could it be that no one cares about the discrimination against a man who has had a letter published in Nature criticizing embryonic stem cell research?

Texas, Adult Stem Cells, Multiple Sclerosis

Opexa is a division of Pharmafronteirs (or it's the other way around, I'm not sure) which is based at the Woodlands, near Houston, Texas.

The company specializes in cell therapies, based on adult stem cells and the controlled manipulation and replication of adult cells.

Multiple sclerosis (MS)is a disease that causes the loss of the myelin around nerves. Think of myelin as insulation that speeds the transmission of nerve signals. When myelin is lost, nerve signals can't go where they're needed, as fast as they are needed. People end up weak, with tremors, and the lack of balance, loss of coordination and the loss of the ability for the muscles that enable us to breathe and cough to function.

We know that MS is a sort of autoimmune disease in most cases. The cells that are supposed to fight infection and keep abnormal or injured cells that can cause cancer actually decide that the myelin needs to be destroyed.

For over 4 years, Pharmafrontiers or Opexa has been running a series of experiments using T cells - the specialized white blood cells that mature in the Thymus and which are supposed to kill foreign cells, like bacteria or cancer cells.

The company has a technique for isolating the patient's specific T cells that attack their myelin, growing them in the lab until they have millions, and then treating them so they can't multiply. The treated cells are then injected under the skin of the patient, and the body really notices the cells, and uses all the immune system to attack them - and all or most of the T cells in the body that act like them. So the myelin is not destroyed anymore - or at least not as fast.


Opexa are now in Phase IIb - meaning that they know it's safe to use in people (Phase I tests) and are finding out more about how much is needed and who can be helped.

There's a great first-person story about someone who is being treated as part of the experiment at "I Have MS."

For a couple of very pretty videos that explain all this much better than I ever could - and the press release by the company about the Phase IIb trial -- take a look at the Opexa site, at this page.

Added:

Opexa is selling the treatment as "Tovaxin™" - a vaccine.

That's how vaccinations work, by the way. Our bodies are convinced to make antibodies and specialized white blood cells to kill or destroy the foreign bacteria, virus -- and someday, cancer and all sorts of cells that inappropriately make those antibodies and attacks against our own normal cells, treating them as though they are damaged or foreign. As long as our bone marrow is healthy, we seem to be able to make a nearly unlimited number of those white blood cells (there's also some "depots" or reserves out in the lymph nodes and in the liver, spleen and the gut lining where the cells lurk and wait for their chance to multiply and fight disease, evidently). And I think this is how "allergy shots" work.

Documentation of stem cell cancer link

From Science Daily, January 22:

U.S. scientists have clarified how normal stem cells become cancer stem cells, as well as how cancer stem cells can cause the formation of tumors.

Dr. Xi He and associate investigator Linheng Li, both with the Stowers Institute for Medical Research, studied the intestinal system in mice in which one of the human tumor suppressor genes, PTEN, had been deleted.

"We found that a loss of PTEN in intestinal epithelial cells accompanied by a loss of PTEN in stromal cells can lead to changes that may increase the number of stem cells and change their position or location," said Li. "These changes result in crypt fission and budding and can lead to intestinal polyposis and uncontrolled tumor growth."

"What we learned," added He, is that "cancer stem cells are a rare population in the tumor mass; that they are slow cycling, but more active than normal stem cells; and that cancer stem cells and stromal insertions initiate the process of primary tumorigenesis ..."

The study appears on the Nature Genetics journal's Web site.

WARF relaxes embryonic stem cell fees and rules

The Wisconsin Alumni Research Foundation holds the patents on virtually all embryonic stem cells that have ever been produced, that ever will be produced, and of all the technological and medical results of that research. At least according to them, and at least in the United States.

And they've been sued by other researchers because of those patents - and not only because of the money involved.

However, early this week the Foundation announced that they will relax some of their earlier restrictions and that they will not charge some researchers for licensing fees. According to the Sacramento Bee,

The Wisconsin foundation that holds patents covering U.S. embryonic stem cell research will waive some of its fees to encourage more industry-sponsored research.

The changes follow criticism from scientists who said the Wisconsin Alumni Research Foundation's fees and its licensing system were driving some investment overseas.

Scientists around the country hailed the policy changes, which will let researchers share their cells for free and allow companies to sponsor research at universities without having to obtain licenses that cost up to $400,000.

"The notion of reducing fees and sharing cell lines and enabling companies to sponsor research at academic institutions is a good thing and should help push the research forward," said Brock Reeve, executive director of the Harvard Stem Cell Institute.

The Wisconsin foundation controls three patents covering research by University of Wisconsin-Madison scientist James Thomson, who in 1998 became the first to grow and isolate human embryonic stem cells. The patents are broadly written to cover the cells and research techniques used by many American scientists.

Nevertheless, the lawsuit will not be dropped, according to SignOn San Diego, by the Union Tribune

But despite the policy changes, the patent challenge will not be dropped, said Loring and John Simpson, of the Foundation for Taxpayer and Consumer rights, one of the groups challenging the patents.

“A change in licensing policy of the human ES cell patents doesn't solve the fundamental problem that the patents should not have been issued in the first place,” Simpson said. “The right thing for WARF to do is admit that it doesn't deserve the patents and abandon them in their entirety.”

Review of Umbilical Cord Pancreas Cells

I've read the unproofed draft (their English is much better than my Korean) of "Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure" by B. Sun, et. al. (Biochem. Biophys.Res. Commun. (2007), doi:10.1016/j.bbrc.2007.01.069)

The authors do not tell us how much of the insulin-secreting cells or colonies of cells they were able to obtain. However, they do report that at one stage, the cells exhibit Oct-4 and "stage-specific antigen 4"(which are characteristic of embryonic stem cells). After inducing umbilical cord cells to revert to these embryonic-like stem cells, they then followed a previously reported protocol for inducing embryonic stem cells into beta islet cells. Colonies of cells grew in islet-like structures and were positive for both insulin and C-peptide. The C-petide is indication that the insulin came from the cells, and not from an artificial source in the nutrients in which the cells were grown.

Time will tell whether the photos are real, whether the results can be replicated in other labs, whether there are enough babies born and cord blood to be obtained to match all the diabetic patients in the world, whether it's possible to transplant immune-matched islet cell structures into humans, and whether those islet cells will survive and function in the recipients. I wonder whether the manipulated cells will be genetically stable or whether they will be prone to die or mutate.

On the other hand, if as in hematopoietic stem cell umbilical cord blood transplants, the cells do not have to be as closely matched in order to be accepted by the immune system, and if these cells persist as long as maternal stem cells have been reported to do, then this report brings us the most promising news of a possible treatment if not cure for diabetes that I've seen in all these years of stem cell reports.

Insulin from Umbilical Cord Cells

Another lead from Wesley Smith and Matthew Epinette at Bioethics.com on a report that Korean researchers have reported in the Korean Times that they will soon publish that they have produced beta islet insulin producing cells from umbilical cord blood. The abstract of the unproofed "in press" article is free here, at the website of the Biochemical and Biophysical Research Communications. You can also purchase access to the unproofed article.

Reference:
"Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure." Bo Sun, (a,b), Kyung-Hwan Roh (a,b), Sea-Rom Lee (a,b), Yong-Soon Lee (a) and Kyung-Sun Kang (a,b). (a)Laboratory of Stem Cell and Tumor Biology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea; (b) Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, South Korea. Biochemical and Biophysical Research Communications doi:10.1016/j.bbrc.2007.01.069
Article in Press, Uncorrected Proof

Received 29 December 2006. Available online 24 January 2007.

Mothers keep on giving

Stem cells, that is.

We have further proof of yet another naturally occuring adult stem cell line that contributes to treatment of diabetes in the recipient long after introduction of the cells and without immune rejection.

Scientists have reported in the "Proceedings of the National Academies of Science (Free abstract) about the discovery that mother's stem cells may cross the placenta and that- in those babies who grow up and later develop Type I diabetes ("Juvenile Diabetes," or "Insulin Dependent Diabetes Mellitis") - some of those cells help repair the pancreas and make insulin.

The researchers thought they would find evidence that the maternal cells might actually cause the diabetes, but instead found that the maternal cells had become beta islet cells of the pancreas, the cells which produce insulin, and were functioning in a beneficial way, years later.

From the online journal, ScienceDaily,

For the first time, scientists have discovered that cells passed from mother to child during pregnancy can differentiate into functioning islet beta cells that produce insulin in the child. The same study also found that maternal DNA was found in greater amounts in the blood of children and young adults with Type 1 diabetes than their healthy siblings and a control group, implying that they may be attempting to repair damaged tissue.
The findings suggest a beneficial role for this type of maternal microchimerism. Microchimerism is the term used when an individual harbors cells or DNA that originate from another genetically distinct individual.

In this study, published in the Jan. 22 issue of the Proceedings of the National Academy of Sciences, J. Lee Nelson, M.D., a member of the Clinical Research Division at Fred Hutchinson Cancer Research Center, and colleagues found no evidence that the mother's cells were attacking the child's insulin cells and no evidence that the maternal cells were targets of an immune response from the child's immune system.

"We think the maternal cells may be helping to regenerate damaged tissue in the pancreas," Nelson said.

She said investigators are excited about new possible approaches to treat Type 1 diabetes raised by their findings. For example, if maternal microchimerism results in cells that make insulin, a mother's stem cells might be harvested and used to treat her diabetic child. Such cells would have a genetic edge over donated islet cells from a cadaver that are usually completely genetically mismatched.

"The child is probably tolerant to the mother's half-matched cells because the child acquired the cells during its life as a fetus while its immune system was still developing," Nelson said.

Originally, the study of 172 individuals and pancreatic tissue from four males was designed to ask the question whether these small numbers of maternal cells might be involved in any way in Type 1 diabetes. "My initial theory was that perhaps, in some situations, too many mother cells cross over to the fetus at the wrong time, becoming beta cells that make insulin in the child. Could diabetes result because the child lost tolerance to those cells because they are genetically half foreign? Our research disproved this," she said.

Instead, the researchers found a small number of female islet beta cells in male pancreatic tissue (procured from autopsies) that produced insulin. "To our knowledge a maternal contribution to endocrine function has not previously been described," the authors said. "Our findings also raise the possibility that naturally acquired microchimerism might be exploited to therapeutic benefit."

The study found significantly higher levels of maternal DNA in the peripheral blood of 94 children and adults with Type 1 diabetes as compared to 54 unaffected siblings and 24 unrelated healthy subjects they studied. Maternal microchimerism first was recognized in children with severe combined immunodeficiency in the 1970s. In 1999, a study by Nelson et al was first to show that maternal microchimerism persists into adulthood for persons with uncompromised immune systems (Journal of Clinical Investigation 104:41-47).

Researchers in the UK also contributed to the report. From the BBC:

Jo Brodie, of the charity Diabetes UK, said scientists trying to perfect islet cell transplantation as a treatment for diabetes faced problems sourcing enough material, and preventing the recipients' immune systems from attacking the newly transplanted cells.

"If cells with the potential to produce insulin can pass from mother to child during pregnancy, without the child's immune system destroying them as seems to be the case here, then this could open up promising new avenues of research, and perhaps provide a new source of insulin-producing cells for therapeutic use."

(That 1999 article is available free online at PubMed Central: "Microchimerism of maternal origin persists into adult life." Maloney S, Smith A, Furst DE, Myerson D, Rupert K, Evans PC, Nelson JL.J Clin Invest. 1999 Jul 1; 104(1): 41-47.PMCID: 408407.)

Where did the stem cells come from in the mother? How are they preserved in the child through the years, even when mom and child would not be considered a good "tissue match" for organ donation? And how are they stimulated and recruited to the necessary tissues and organs in order to contribute to the repair and function of the child's tissues? How can we mimic and maximize the process when and where we want?

All of these questions are fertile ground for research. And not a one of the answers will depend on the destruction of a human being.

There's coverage in the January 22 Washington Post. However, the article states that Type I diabetes is inherited. The tendency may be inherited, but I don't believe that anyone has determined the actual gene or any specific trigger that can be said to cause Type 1 diabetes, other than the patiint's own immune system begins to make antibodies against the beta islet cells and insulin. Somehow, the mother's cells aren't affected in this case - which makes the discovery even more important and hopeful for patients: there has always been the concern that any new stem cells introduced into the patient would also be subjected to attack.

More information on Type 1 diabetes at E-Medicine.com (a very reliable site for medical information) and from The American Academy of Family Physcians. That last link is courtesy of the Post.

Hat Tip to Wesley Smith and Matthew Eppinette at Bioethics.com (as well as my Google News Search alerts).

Nanofiber Scaffolds for Neural Stem Cells (and some truth)

Johns Hopkins researchers report that they have developed "nanofibers" impregnated with special proteins which allow them to grow neural stem cells from embryonic stem cells without "requiring high concentrations of growth factors."

One of the researchers, Neuroscientist Hongjun Song, comments on the immediate results of the research, which will not include actual patient therapy:

“Eventually, stem cells will be very important for treating disease using cell replacement therapy, but more immediately stem cells offer the opportunity to model human disease and find ways to screen for therapeutic drugs to treat the disease.”

Song is a member of the body which oversees stem cell research at Johns Hopkins, the "Stem Cell Policy and Ethics Program." This means that even though he has a vested interest in maintaining his own lab and promoting his research, he is among those at Johns Hopkins who determine how to follow the institution's mission:

• Facilitate the ability of the public to benefit from advances in cell engineering in morally responsible ways;
  
  
• Anticipate moral and policy challenges in stem cell science and cell engineering; and


• Provide opportunity for careful and interdisciplinary analysis of these challenges that will be of assistance to both policymakers and the public.

The inclusion of Song in justifying and lobbying for his own work under the guise of "ethics" is a serious conflict of interest and can not be called "morally responsible."

The good news is that some people see an end to the use of embryo destruction. From the article posted earlier today on trading eggs for in vitro fertilization fees:

In any case, the need for eggs may only be temporary.

They are, in fact, only a tool to reprogram the inserted DNA so that it will drive the development of an early embryo. Scientists hope to learn enough about that reprogramming process to let them take an ordinary cell from a person and use it to produce other kinds of cells, perhaps without going through an embryo stage. That might happen in 10 years, Murdoch estimated.

And then they wouldn't need eggs any more.

Trading eggs for fertility treatment

Women who are desperatly trying to get pregnant, but who cannot afford to pay $5,000 - $6,000 for in vitro fertilization may be offered lower IVF fees in exchange for donation of some of their oocytes for research in the UK. The Human Fertilization and Embryology Authority approved the trades for one lab last July, but are now seeking public comment, according to an Associated Press article.

The limiting factor for embryonic stem cell research has never been the restrictions placed on US Federal funding. The problem is obtaining eggs from women.

So far, the track record for altruistic donations is mixed. On one hand, hundreds of women volunteered to donate eggs in South Korea for research by the now-disgraced scientist Hwang Woo-suk, who fraudulently claimed success in therapeutic cloning.

But Dr. Robert Lanza, vice president of research and scientific development at Advanced Cell Technology Inc. of Alameda, Calif., said he has given up trying to get donations without compensation. After more than a year of pursuing that strategy and about 100 advertisements, ACT was able to get only one woman to donate eggs, he said in an e-mail.

And Kevin Eggan of the Harvard Stem Cell Institute, who's been seeking eggs since May in return for reimbursing out-of-pocket expenses, said recently that the effort had generated some calls but no donors yet. The approach must be given more time to work, he said.

Murdoch, who also directs a fertility treatment center in Newcastle upon Tyne, said that when her lab asked fertility-clinic patients to donate eggs, it received only 66 over seven months. That's just not enough, she said.

In contrast, if her new plan attracts two women a week — chosen because they appear likely to produce lots of eggs — it would provide 20 eggs each week. That's still not a lot, but the supply should be steady, she said.

Her "egg-sharing" plan resembles an arrangement that's used occasionally at fertility clinics. In that plan, a woman shares her eggs and treatment costs with another woman who wants a baby.

Murdoch's group has permission from Britain's Human Fertilization and Embryology Authority to set up the arrangement for stem cell research. Now it's a question of raising money to finance it. Murdoch said she hopes to start offering the deal to British women in a few months, and that she has already heard from dozens of women eager to participate.

Though the HFEA approved Murdoch's plans in July, it has since started gathering public and expert opinions on whether egg sharing should be permitted. "If the consensus is that this is not a good idea, we can change the policy, and rescind the license," said John Paul Maytum, an HFEA spokesman.

Proof there's no stem cell "ban"

Wesley Smith, at his blog Secondhand Smoke, notes that American Cell Technology has received a grant from the National Institute of Health for research on embryonic stem cells. He also points out what should be obvious: ACT must have received this funding for research on the stem cell lines that are authorized under President Bush's August, 2001 policy.

(In case you can't remember who ACT is, they're the organization that claimed to have cloned human embryos back in 2001, and who claimed to have found a way to produce embryonic stem cells without killing the embryo when in fact they killed every one of those human embryos they used. The company is one of the best examples of the sort of ethics that make people like me think of "ethics for sale." ACT has employed ethicists Art Caplan and Glenn McGee and is very closely associated with Geron, WARF (the research foundation at the University of Wisconsin).

So much for the myth that these cells can't be used or that there is any sort of "ban."

The focus of the research is basic research on how Embryonic Stem Cells divide and differentiate.

From the Washington Business Journal:

The money will support an ongoing collaboration between Alameda-based Advanced Cell (OTCBB: ACTC) and The Burnham Institute of Medical Research in La Jolla.
Researchers are investigating the genetic mechanisms and proteins believed to control how basic embryonic stem cells develop and differentiate. That understanding is essential in harnessing the regenerative powers of stem cells in medical applications, the company says.

This is very basic research, not an actual attempt to produce cells for use in treatments. Hopefully, the added knowledge will point to ethical, non-destructive ways to obtain stem cells for treatment in actual patients.

Support science and human rights for all

That's the point that Yuval Levin makes in his New York Times op-ed piece (free registration required), "A Middle Ground for Stem Cells," today. The essay is also available online at the International Herald Tribune.

It is, to begin with, not about stem-cell research, any more than an argument about the lethal extraction of livers from Chinese political prisoners would be a debate about organ transplantation. There are ethical and unethical ways to transplant organs, and there are ethical and unethical ways to conduct stem cell research. The question is to which category a particular technique — the destruction of living embryos for their cells — belongs.

The debate is also not about whether there ought to be ethical limits on science. Everyone agrees there should be strict limits when research involves human subjects. The question is whether embryos destroyed for their cells are such human subjects.

But that does not mean the stem-cell debate is about when human life begins. It is a simple and uncontroversial biological fact that a human life begins when an embryo is created; its human life will last until its death, whether that comes days after conception or many decades later.

But that does not by itself settle the ethical debate. The human embryo is a human organism, but is this microscopic being — with no self-awareness and little resemblance to us — a person, with a right to life?

Many advocates of embryo-destructive research argue that the human embryo is just too small, too unlike us in appearance, or too lacking in consciousness or sensitivity to pain or other critical mental capacity to be granted a place in the human family.

But surely we have learned the hard way not to assign human worth by appearances. Surely we would not deny those who have lost some mental faculties the right to be regarded with respect and protected from harm. Why should we deny it to those whose faculties are still developing?

At its heart, then, when the biology and politics have been stipulated away, the stem-cell debate is not about when human life begins but about whether every human life is equal. The circumstances of the embryo outside the body of a mother put that question in perhaps the most exaggerated form imaginable, but they do not change the question.

The evidence of nature sometimes makes it very hard to believe that all human beings are equal. It takes a profound moral case to defend the proposition that the youngest and the oldest, the weakest and the strongest, all of us, simply by virtue of our common humanity, are in some basic and inalienable way equals.

Our faith in that essential liberal proposition is under attack by our own humanitarian impulses in the stem-cell debate, and it will be under further attack as biotechnology progresses. But the stem-cell debate, our first real test, should also be the easiest. We do not, at least in this instance, face a choice between science and the liberal society. We face the challenge of championing both.

President George W. Bush's stem cell policy seeks to meet that challenge. It encourages scientists to pursue the cells they seek without destroying life.

Please consider reading the rest at one of the links above.

Calling all scientists

The Aspen Ideas Festival is a meeting that I had never heard of until recently (I actually found it Googling for "Bioethics and Politics" and "Bioethics and Policy" which are names I've come up with for alternative blogs in case I decide to change my focus) There are audio recordings and transcripts online which contain segments that should be fascinating to many of us, whether our primary interest is religion, politics or bioethics.

If you want to see who are considered the elite thinkers in this country - at least by others who consider themselves elite thinkers - take a look at the website and listen or watch some of the sessions from the July, 2006 event.

One segment is audio-only, "Politics and technology." Nigel Cameron links to it on his blog, and he was the sole prolife member of the panel. Other panel members include Neal Lane, a professor of Physics and Astronomy at Rice University at Houston, Texas and Assistant to the President for Science and Technology and Director of the White House Office of Science and Technology Policy from 1998-2000, Doroth Shore Zinberg, a sociologist and lecturer in Science, Technology and Public Policy at Harvard, and Lawrence Krauss, a professor in Physics and Astronomy who has written The Physics of Star Trek.

The one thing that all of the panelists agreed to in the very enlightening hour and a half, is that all of us should become involved in policy making, whether it's in politics, our professional associations, or in teaching about science and ethics in our local communities and churches. I love it when people so much more brilliant than I agree to even part of the mission and vision that I wrote for LifeEthics:

We encourage all of our members, especially medical and scientific professionals, to become involved in setting the policies of their communities, associations, schools and businesses in order to ensure that those organizations maintain high ethical standards.

We educate the public and professional communities on current events concerning the right to life and liberty of humans. Our members mentor one another in opportunities to serve in professional and academic capacities to fulfill our mission. We monitor and alert our members and the public about unethical scientific research and medical therapy. We are active in our own institutions and associations in order to influence the policy decisions of the organizations that represent us.

We use standard scientific and medical definitions and verifiable scientific data whenever possible in our position statements and deliberations and expert opinions only when the evidence is not available.

(The full panel would not be in agreement with the section that is struck.)

David Prentice's Science rebuttal

This week, Science Magazine, has published a Letter to the Editor (sorry, subscription only) by David Prentice, Ph.D., in response to the letter by Smith, Neaves and Teitelbaum from last July.
(That was the letter which prompted Michael Fumento to dub the Journal "PseudoScience.")

In his letter, Dr. Prentice points out that the "Supporting Online Material" from the first letter actually contradicted the accusations of the three.

Will we have a series of rebuttals to the rebuttals, now?

Bioethicists aren't needed

Well, they didn't come right out and say it.

Moreno and Berger are still stomping their feet at Ramesh Ponnuru for doing his job. After all, he's an editor for a magazine covering "Republican/conservative news, commentary, and opinion."

Moreno has a Ph.D. in philosophy, and Berger is an Assistant to Moreno and two other Fellows at the socialist "Center for American Progress Institute for Bioethics. I suppose that it could be said that they are doing their jobs, too, except for the way they argue their point.

They argue that scientists and the "scientific community" do not recognize that there are "viable alternatives" to embryonic stem cells. Because they are certain of this opinion, they have attacked a report that proposes research "Without Destroying Human Life."

If these two bioethicists are so certain that that scientists are the final authorities as to what should be done, what is their justification for "bioethicists" (other than to make arguments for the scientists who lead them, that is)?

Progressives vs. Conservatives (rubber, glue)

What did I tell you? I forgot to tell you what the "Progressives" fuss was about and to link to the actual articles. Which meant that I didn't review the actual critiques of the report by the President's Domestic Policy Council (covered here, last week).

Jonathan Moreno and Sam Berger of the Center for American Progress' Bioethics Project wrote "Alternative Sources of Stem Cell Truth: White House Misrepresents Potential of Alternative Sources of Pluripotent Stem Cells" on January 11th. Ramesh Ponnuru critiqued their critique in "Selling Alternatives Short: Good news for humanity is bad news to some" at the National Review OnLine. Moreno and Berger wrote a rebuttal, "Shouting Semantics Over Science."

It's easy to dismiss the fussin' as political differences or competition between rival publications (although I doubt that NRO has much to worry about). However, what is at stake is the very basis of ethics, itself: the primary philosophical questions "who am I, why am I here, what should I do?"

There's also the secondary question, "how can I keep that other guy from killing me?"

Some of us believe that it is never ethical or permissible to destroy human embryos, even if it means that we never obtain the treatments that Moreno and Berger mention in their first article. Moreno and Berger believe that research should not be hampered by concerns for human embryos, even though every single possible therapy that they mention is just as likely to come from non-destructive therapy. (anyone who doubts that there is already research supporting non-destructive sources for each and every line M & B mention can try PubMed, review this blog, or email me for the address where they can send their self-addressed stamped envelope and payment for the hard copies of the pertinent research.)

It's true that I agree with Ponnuru,

Again and again, this duo treats readers to double standards. Alternative approaches can be dismissed whenever promising findings haven’t been reproduced; but findings favorable to embryonic stem-cell research are taken to the bank, whether or not they’re reproduced. The long-term potential for embryo-destructive research is emphasized; the failure of alternative approaches to produce immediate results is held against them. Data is cherry-picked to show that the absence of taxpayer funding for embryo-destructive research has hurt American competitiveness; contrary evidence is ignored.

One of the great fake bits of data in this debate — the “400,000 excess embryos stored in fertility clinics” — makes a return appearance. To repeat: We know that number from a study that also showed that fewer than three percent of those embryos would be available for research.

Let's face it, the goal of all stem cell research is to manage functioning tissue, organs, and cells. These are made by adult stem cells. The embryonic stem cells and even the fetal/amniotic/placental stem cells are more primitive or intermediate forms of stem cells similar to the the Multipotent Adult Progenitor Cells (MPACs), not the specific stem cells or stem cell lines that are desirable for in vivo use. Animal models, umbilical cord, amniotic/placental, and MPACs, along with our experience with actual adult stem cells should be sufficient, without killing human embryos, without creating new embryos for destruction, and without cloning or creating animal-human hybrids.


Besides, the true goal should not be the ability to implant actual cells and organs, except in dire emergencies - what we really want is to be able to regenerate our heart, brain, kidney, pancreas and skin cells in place, as we lose or injure them.



HT to Jivin' Jehosaphat

Selecting stem cells, filtering cancer cells

I've wondered how the stem cells were being harvested from blood, instead of from bone marrow, and here's an explanation printed in Science Daily about the work of Professor Michael King. The author did a good job of explaining a complex process. Although I haven't copied it here, the article also explains one way that cancer spreads.

During inflammation, the vascular wall presents surface selectins that adhere specifically to white blood cells. These selectins cause the white blood cells to roll slowly along the vascular wall, seeking signals that tell them to crawl out of the bloodstream. This is how white blood cells migrate to bacterial infections and tissue injuries. King set out to find a way to duplicate this natural process.

First, he noted that the selectins form bonds with the white blood cells within fractions of a second, then immediately release the cells back into the bloodstream. He also realized that selectin is the adhesive mechanism by which bone marrow stem cells leave the bloodstream and find their way back into bone marrow. This is how bone marrow transplantation works. Finally, he learned that when a cancer cell breaks free of a primary tumor and enters circulation, it flow through the bloodstream to a remote organ, then leaves the bloodstream and forms a secondary tumor. This is how cancer spreads. He put these facts together with one more, very important fact: the selectins grab onto a specific carbohydrate on the surfaces of white blood cells, stem cells, and cancer cells. Associate Professor King decided to capture stem and cancer cells before the selectins release them.

Harvesting Stem Cells

Because bone marrow stem cells stick to selectin surfaces more strongly than other cells, King’s group coated a slender plastic tube with selectin. They then did a series of lab experiments, both in vitro and in vivo using rats, with this selectin-coated tube to filter the bloodstream for stem cells. It worked, and the King Lab discovered that they could attract a large number of cells to the wall of their selectin-coated device, and that 38% of these captured cells were stem cells. King envisioned a system by which doctors could remove stem cells from the bloodstream by flowing the cells through a device, and make a more concentrated mixture containing, say, 20-40 percent stem cells. These stem cells could then be used for tissue engineering or bone marrow transplantation.

This is a non-controversial way of obtaining stem cells that can be differentiated into other, useful cells.

Projection, distraction about embryonic stem cells

Ignoring the ignoble vote in the House of Representatives today, and without a prior posting about the recent report concerning amniotic and placental stem cells, Art Caplan has posted a little political rant about the politics of stem cells. Caplan is a pseudoeditor over at blog.bioethics.net has once again claimed that someone else is telling lies.

Blog.bioethics.net is the blog of the editors of the Journal of American Bioethics. We shouldn't forget that both Caplan (a frequent poster, but not an editor) and the AJOB Editor-in-Chief Glenn McGee, once worked for Advanced Cell Technology and that Caplan is also one of the advocates of the Progressive Bioethics Initiative. (McGee has spoken about the contrast between the AJOB blog and conservative blogs, such as Wesley Smith's "SecondHand Smoke," which he (McGee) calls a "reactionary blog" at the Initiative's "Future of Progressive Bioethics," in April, 2006.)

Caplan doesn't work very hard at explaining his viewpoint, although his title indicates strong feelings:" White House Plays Politics, Again, with Science; Just One Lie After Another..." He then calls the recent report on stem cell research by the Domestic Policy Council the "Ridiculous Report."

No one knows if adult stem cells or fetal cells will perform in the same way as embryonic stem cells. No one knows much of anything about any of the science because it is all new.

The actual name of the report is "Advancing Stem Cell Research without Destroying Human Life." In the report, I don't see any claim that Dr. Atala has said that funding for embryonic stem cell research should be limited in any way. What I do see is a blurb about the new report and,

While the research is still developing, Dr. Atala and his team believe that these amniotic stem cells may be fully as flexible as embryonic stem cells, while having additional medical advantages: they are easier to grow than human embryonic stem cells, and they do not form tumors (a problem that has plagued embryonic stem cell use). And since amniotic stem cells can be collected without destroying human life, they avoid the ethical dilemmas.

But, of course, Art doesn't know the long-term results of destructive embryonic research. Which is pretty shabby reasoning to encourage research that goes against the traditional ethic that science and medicine shouldn't set out to sacrifice one human life for another. In that old ethic, "self-" usually came before "sacrifice."

The business of adult stem cells

Since Mr. Reed has urged us to follow the money trail, and after my talk with the banker last week, I was pleased to see that others are looking at ethical stem cells as an investment.

The business journal, Bloomberg, reported on several companies that are involved in ethical stem cell research. Evidently, these companies received a boost in their ratings after the news of amniotic stem cells broke over the weekend.

(HT to Rush Limbaugh)

"Con-Job" "Deception" (Amniotic Stem Cells)

Don C. Reed, a rabid supporter of embryonic stem cell research - and, it seems, only stem cell research - has written an editorial, "Coincidence or Con-Job?" He flatly states that he believes that we are witnessing an act of "weapons of mass deception" in the timing of the release of the newest issue of Nature Biotechnology, containing Anthony Atala's report on amniotic/placental stem cells.

Fortunately, the editorial (a classic case of projection if I ever saw one) is so far only to be found on blogs such as "Stem Cell Battles" (there's no permanent link that I can find, but it's labeled "#278," and dated January 8, 2007) and email-lists, like Steven Meyer's "Stem Cell Information" on Yahoo Groups.

But what I feel in my gut is:

Weapon of mass deception.

Just as non-existent weapons of mass destruction were used to sell America on the idea of invading Iraq, I think this sudden (and hugely publicized) "breakthrough" will turn out to be less than it appears—and it will be used to try and block embryonic stem cell research

and

And now, just before the debate to loosen those restrictions, suddenly a miraculous discovery makes it seem we don’t need embryonic stem cell research?

I don’t buy it.

It may be strictly a coincidence that the allegedly miraculous breakthrough is announced just hours before the vote: providing cover for legislators looking desperately for some excuse to avoid supporting research that may cost them votes from the Religious Right.

It may also be a coincidence that “the technology described in the study is owned by Wake Forest University Baptist Medical Center…”(emphasis added)(in original, BBN) -- a religion officially opposed to embryonic stem cell research. –quoted material from Los Angeles Times, “Stem Cells in Amniotic Fluid…” by Karen Kaplan, January 8, 2007.

Dr. Atala, it should also be noted, sits on the board of Plureon Corporation, a biotech startup company connected to the experiment. I do not know the nature of their relationship, and there would be nothing wrong with a scientist profiting from his invention; still the money trail is part of the equation.

But the biggest question is simple: is the experiment important?

If an adult stem cell “breakthrough” turns out to be real—that would be not only good, but expected.

"Able to become all tissue types"

That's the claim by Dr. Anthony Atala in an interview with Gwen Ifill of PBS.

So these cells actually have been in the amniotic fluid for many years, and we've known about their presence for many years. The major finding in this study is the fact that we found a stem cell population that is a true stem cell, in terms of their nimble ability to become all tissue types.

GWEN IFILL: So does this end the argument that we've been having all these years about stem cell research?

DR. ANTHONY ATALA: It does not, mainly because it's another stem cell choice. And I think you really can't tell which cell is going to be best for which indication, and all cells have advantages and disadvantages.

Of course, the disadvantage of Embryonic Stem Cell Research is that a human embryo must be destroyed.

"Pluripotent" Amniotic/Placental Stem Cells

I've just skimmed the Nature Biotechnology article (free abstract and references with free registration to Nature.com, the article is for subscription or by individual purchase, only)by Atala, De Coppi, et. al, "Isolation of amniotic stem cell lines with potential for therapy" (Nature Biotechnology - 25, 100 - 106 (2007). Published online: 7 January 2007; | doi:10.1038/nbt1274)

The authors claim that the cells are pluripotent. This is not being publicized as much as I would like it to be. Please, when you call your Representative and Senators about the vote that is planned for Thursday, on HR 3, please let them know that these cells may, indeed, be more useful and are much more ethically acceptible than embryonic stem cells from "spare" embryos.

The cells can be obtained from placenta as well as amniotic fluid, so can be harvested without risk to the baby.

The cell lines were evaluated through 120 doublings and appear to be stable. All cell lines were confirmed in mice, using human stem cells implanted into mice that are immune-deficient. There were no teratomas. The human cells repaired damage in the mouse brains, in mice with a disease similar to Krabbe's disease. While the production of dopamine is not documented, the cells also developed along the lines of dopaminergic cells - the cells that are diseased in Parkinson's.

While the use of human nerve cells in the mouse brain could be considered ethically problematic, this is a very significant finding.

The researchers report that they were able to produce several lines of cells, and to prove that some of these cell lines are functional.

"We conclude that the AFS cells are indeed broad-spectrum multipotent (that is, pluripotent) stem cells."

Potential sources of AFS cells in the developing fetus are diverse31.
CD117 (c-Kit), the surface marker used for immunoselection of AFS
cells, plays an important role in gametogenesis, melanogenesis and
hematopoiesis32,33. This receptor protein is present on human ES
cells34, primordial germ cells and many somatic stem cells, including,
but not limited to, those of the neural crest35,36. Despite sharing
expression of c-Kit, AFS cells appear clearly distinct from ES cells, germline stem cells and certain adult stem cell populations, such as hematopoietic stem cells, on the basis of differences both in a variety of cell surface markers and in gene expression patterns assessed by transcriptional profiling37. Thus, the role of AFS cells in ontogeny is not yet clear.
AFS cells can serve as precursors to a broad spectrum of differentiated cell types. We used retroviral marking of AFS cell clones to rigorously assess their multipotent character. Cells from a marked clone were induced to differentiate along six distinct lineages (adipogenic, osteogenic, myogenic, endothelial, neurogenic and hepatic). DNA of the resulting specialized cells contained a unique marker junction fragment between proviral and cellular sequences in the genome. In addition to the markers and cell types documented here, we have demonstrated that human AFS cells of the same clone can be induced to express markers characteristic of cardiac muscle, including cardiac myosin, troponin I and troponin T, and of pancreatic beta-cells, including Pax6, neurogenin D and insulin (data not shown). Human AFS cells can therefore yield differentiated cells corresponding to each of the three embryonic germ layers. The full range of adult somatic cells to which AFS cells can give rise remains to be determined.

. . .

AFS cells are able to differentiate along adipogenic, osteogenic,
myogenic, endothelial, neurogenic and hepatic pathways.We show the
acquisition of lineage-specific functionality by AFS cells differentiated
in vitro toward neurons, osteoblasts and hepatocytes. For some cell
types, acquisition of a full terminally differentiated phenotype is
difficult to achieve in culture. The expression of characteristic functions
may demand multistage protocols, as exemplified here by the
expression of GIRK channels after neurogenic differentiation. Similarly,
we observed urea secretion after hepatogenic differentiation. This
represents a liver-specific function that requires the coordinated
expression of several enzymes and specific mitochondrial amino
acid transporters.

Note - edited for the spelling of De Coppi, and for a correction concerning "Krabbe's Disease." (The disease treated with fetal stem cells was "Batten's Disease."

No Debate, No Amendments on Embryonic Stem Cell Bill

From the Sun Chronicle

Democrats have an agenda for the first 100 hours of the new session that includes ethics reform, a higher minimum wage, more stem cell research and lower student loan costs.

Those bills are being debated under what is called a closed rule, under which no amendments are allowed.

They are being proposed directly from the Democratic leadership, without the benefit of committee hearings.

We must call our Representatives and our Senators about the Castle-DeGette Bill, HR 3 and S 5.

We keep saying, "There is no 'ban.' There's already taxpayer funding for both ethical stem cells and for the few stem cell lines that the President authorized (after the Clinton administration made the commitment to buy them).

We can talk and write and blog all week on the stem cells from amniotic fluid, umbilical cords, the placenta and in the target organs themselves. We can discuss "niches" and local environments, factors and markers.

Very little of this positive talk about ethical stem cell research is being heard.

"It's a matter of taste."

Bioethics.com has posted a YouTube video from the Ali G show with Dr. Edmund Pelligrino (identified as from "Georgetown University, Papal Advisor Medical Ethics"), Richard Fischer ("American Institute of Homeopathy), Dr. John Freeman ("Johns Hopkins Medical School") and Louis Brescht ("Catholic Medical Association"). The segment can also be viewed here, identified as "Ali G - Medical Ethics."

For more information, you may want to read this article at the American Enterprise Institute that explains how one man escaped the same fate.

I'm incredibly impressed with the way the men who find themselves in an obviously ridiculous position behaved. No one was angry, no one was condescending, and they seem to be trying to teach, almost kind.

Now, I have to figure out whether my posting all this information about the circumstances as well as the links makes me as gullible as the men that were fooled by Sacha Baron Cohen. Especially since I have to admit that, although I thought I recognized the interviewer as the same man who plays "Barat," but know I didn't have a clue who "Ali G" was until I googled the name.

Cow-human hybrid ban "would cost patient lives."

The pushing of limits never stops.

First, as far as we know, no one's been able to make an embryo by injecting the nucleus of a human into the emptied cell of a cow oocyte. If they have, they aren't publishing the results and there's definitely no reports about stem cells from the results.

However, the BBC News and USAToday are now telling us that if the UK authorities refuse to license researchers who wish to do this research, then cures for "even Alzheimer's disease" are at jeopardy and threatened. The Telegraph claims that a ban "would cost patient lives."

The Times tells us that these embryos are

. . . are purely for laboratory use and will be used in the valuable search for genetic causes of such deadly afflictions as motor neuron disease. Animal eggs are far easier to harvest than human ones, but once emptied of their DNA can be used to produce an embryo that is more than 99.5 per cent human. They are therefore not technically hybrids or chimeras and there is no question of such embryos being implanted in a womb — which is already illegal.

I'm reassured, aren't you? Especially since the Times goes on to imply that our real problem is that we don't understand what the smart scientists are doing, and an Editorial in Nature (sorry, subscription only) warns of a "quagmire" if scientists allow the public to regulate them.

At least the controversy brings up the fact that harvesting eggs from women is not "practical."

Several stem cell experts submitted applications for a license to create human stem cells using animal eggs. The process involves injecting an empty cow or rabbit egg with human DNA. That would produce an egg with human genetic material inside, with minute traces of animal genetic material.

After a burst of electricity, the egg would be tricked into dividing regularly, becoming a very early embryo from which stem cells could be extracted.

Removing the animal's nucleus ensures that it would not be a chimera, or human-animal hybrid. "When you remove the nucleus with its DNA, you remove the species identity of the egg," said Dr. Stephen Minger, director of the stem cell biology laboratory at King's College. The proportion of animal to human genes would be tiny, with 13 animal genes versus 30 000 human genes.

Minger and colleagues applied for licenses to do this kind of work to better understand degenerative diseases at the cellular level, with the aim of finding targets for new drug treatments. The embryos would not be allowed to develop for more than 14 days.

Using human eggs is not practical because transferring genetic material into a host egg is extremely inefficient. In addition, there are too few human eggs available. Scientists say they would be lucky to get two or three human eggs in one month. In contrast, they could easily get 200 cow eggs in a single day.

All of this makes the research sound like a given. It's anything but.

There was a report out of China that embryos were created using rabbit oocyte cell bodies and human nuclear material. (Articles from 2003: a report from the Washington Post here and the abstract of the original article in Cell Research, here.)The embryonic cells that resulted supposedly manufactured human proteins and appeared to follow human development. Last January, researchers were asking for permission to repeat this experiment in the UK. I haven't been able to find reports that this sort of Somatic Cell Nuclear Transplantation or cloning of hybrid or human-animal embryos has ever been replicated in other labs, or whether the stem cells from this report have been examined by other researchers.

As I wrote yesterday, there is no way to discover how normal or abnormal these cells - if they are ever produced in other labs - is by implanting them in humans.

And, of course, the real ethical question is whether or not the embryos would be "human." If they produce human embryonic stem cells, I would say, "yes." And it is not ethical to destroy even
"potential" human lives in research.

Visitor Number 10,000 could help

It took over a year, and some of those visits are my own viewing of my posts, but sometime this weekend I should have my 10,000th visit to LifeEthics and 15,000th page view. I'm hoping that one of my visitors can help me.

Imagine all of the bloggers who have more audience than I do. And how many of them are prolife and deal with Bioethics. Then, will someone please tell me why the mainstream press still doesn't get it that embryonic stem cell research is a dead end?

Today, my husband and I visited his banker who spoke about his plans for investment this year. The man didn't really understand what I do, but he named "stem cells" as his first option!

I encouraged him to look into those companies that are investing in ethical research, using adult and umbilical cord cells. However, when I tried to name some companies, I realized that I know some of the "bad guys," but not the "good guys" or how to evaluate them.

Evil (UK) restrictions (no hybrids), again

The sky is falling, once again, because of those evil pro-life people who want to kill patients because oppose placing human DNA in cow eggs:

Scientists say disease research at risk after 'knee-jerk' reaction to embryo proposals
LYNDSAY MOSS HEALTH CORRESPONDENT (lmoss@scotsman.com)

VITAL research into devastating diseases could be put in jeopardy because of government opposition to plans to create part animal-part human embryos, it was claimed yesterday.

But scientists hoping to use the technology to create treatments for serious illnesses such as Alzheimer's and motor neurone disease say they must be allowed to continue their work.

Professor Ian Wilmut, from Edinburgh University, leader of the team that created Dolly the sheep, was preparing his application for chimera research when the government said such work should be outlawed - at least initially. Yesterday, he joined scientists from London and Newcastle, who have submitted proposals for similar work, to call for a rethink by the government and the Human Fertilisation and Embryology Authority (HFEA), which issues licences for such studies.

They believe the views expressed by scientists during the consultation on fertility laws were submerged under a mass of responses opposing such research generated by organised campaigns by pro-life groups.

New Poll on Embryonic Stem Cell Research

Before I comment on the poll, please take another look at the statement that I published earlier by Maureen Condic, Ph.D.:

“. . . there is no compelling scientific argument for the public support of research on human embryos.” . . . Immune rejection, tumor formation, and embryonic development have proved themselves to be profoundly serious scientific challenges, and they are likely to remain so for decades into the future.

Unfortunately, this is not what the public is hearing. The media is focusing on the hype of future possibilities for embryonic stem cells, rather than reports of current, real advances in adult and umbilical cord stem cells that have resulted in treatments for diabetes (both adult and juvenile),functioning liver cells Lou Gehrig's Disease (ALS) and lung cells, improvement in patients with spinal cord injury, arthritis, and even lupus and multiple sclerosis.

The news today about a new poll is discouraging. You can read the press reports - and about the increased stock prices for biotech companies due to the bill in question - at Forbes, Bloomberg, and BioResearch Online. The actual poll by "The Civil Society Institute" is available online at the in pdf at their website.

There are flaws in the actual poll. However, I'm afraid that the problem is that people believe that their hope is in embryonic stem cell research.

Here are some of the questions from the poll:

From the statement before question C5 (this question was used in the 2004 and 2005 polls):

Embryonic stem cells are special cells that can develop into every type of cell in the human body. The stem cells are extracted from frozen embryos in fertility clinics, donated by couples who no longer want or need the embryo. This process destroys the embryo. These stem cells can then reproduce on their own, creating what is called a "line" of stem cells that many researchers can work with. Scientists believe that there is a chance that stem cells can be developed into cures or treatments for diseases such as cancer, Parkinson's, Alzheimer's, juvenile diabetes, and spinal cord injuries.

Why is Alzheimer's still in this list?

Question C6

Leaders of the new Congress have indicated that their “first 100 hours” will include introduction of a bill that would reverse President Bush’s restrictions on stem cell research and expand federal funding for research on stem cells that are developed from embryos frozen in fertility clinics and which otherwise would be discarded. Would you strongly support, somewhat support, somewhat oppose, or strongly oppose the new Congress moving ahead in this way with stem cell research in its first 100 hours?

Question C7

Some people say that gridlock on such major issues as stem cell research is one of the reasons why Americans are so frustrated with elected officials in Washington, D.C. Would you say you strongly agree, somewhat agree, somewhat disagree, or strongly disagree with this?

Maureen Condic in First Things on Embryonic Stem Cell Research

“. . . there is no compelling scientific argument for the public support of research on human embryos.”

Memorize this sentence before you call your Congressman and Senators about next week's vote on the DeGette-Castle Bill (they're also calling it the "Stem Cell Research Enhancement Bill,"). You can tell them that your source is this month's First Things article, by Professor Maureen Condic. Please do go read it - it has no flaws that I could find. (and I argue with everyone)

Maureen Condic, Ph.D., is a professor of Neurobiology and Anatomy, an expert in the outgrowth of neurites and guidance of axons of embryonic neurons as well as a critic of destructive human embryonic stem cell research. Her scientific reports are published in prominant peer-reviewed journals such as the Journal of Neuroscience and cited by numerous other scholars.

Back in 2003, she commented on the dismissal of the human embryo as "not a human,"

Embryos are genetically unique human organisms, fully possessing the integrated biologic function that defines human life at all stages of development, continuing throughout adulthood until death. The ability to act as an integrated whole is the only function that departs from our bodies in the moment of death, and is therefore the defining characteristic of “human life.”

This month, Dr. Condic notes that embryonic stem cells most often simply die when implanted in post-natal animal models. If they don't die, they do not yield any therapeutic benefit. Instead, they cause benign and embryonal tumors, there's no evidence that this concern will be resolved in the near future and there really is no way to determine whether any stem cell line is harmless or useful or non-tumerigenic until it's implanted.

The failure of embryonic stem cell–derived tissues to survive when transplanted to adult tissues strongly suggests that science has not yet determined how to generate normal adult tissue from embryonic stem cells.

and

“. . . there is no compelling scientific argument for the public support of research on human embryos.” Serious scientific challenges are, by definition, problems that have stubbornly resisted the best attempts of science to resolve them. Over the past thirty years, hundreds of billions of dollars and countless hours of research by dedicated professionals worldwide have been devoted to solving the problems of immune rejection and tumor formation, yet these issues remain serious scientific and medical challenges. The mysteries of embryonic development have been plumbed for more than a hundred years by some of the most brilliant biologists of history, and yet, despite the clear progress we have made, we are nowhere near the point of having a “recipe book” for cooking up cellular repair kits to treat human disease and injury. Immune rejection, tumor formation, and embryonic development have proved themselves to be profoundly serious scientific challenges, and they are likely to remain so for decades into the future.

The hubris of scientists in the field of embryonic stem cell research who confidently asserted “Give us a few years of unrestricted funding and we will solve these serious scientific problems and deliver miraculous stem cell cures” was evident in 2002, and it is even more evident today. For the past five years, researchers have had completely unrestricted funding to conduct research on animal embryonic stem cells, and yet the serious scientific problems remain. They have had every conceivable tool of modern molecular research available to them for use in animal models, and yet the serious scientific problems remain. Millions of dollars have been consumed, and hundreds of scientific papers published, and yet the problems still remain. The promised miraculous cures have not materialized even for mice, much less for men.

One more thing on errors

That letter mentioned above actually noted nine, not seven, treatments.

Here's the opening paragraphs from the letter (Sorry, subscription only) (Note the uses of "treat," "cure" and "phases"),

Originally published in Science Express on 13 July 2006
Science 28 July 2006:
Vol. 313. no. 5786, p. 439
DOI: 10.1126/science.1129987

Letters
Adult Stem Cell Treatments for Diseases?
Opponents of research with embryonic stem (ES) cells often claim that adult stem cells provide treatments for 65 human illnesses. The apparent origin of those claims is a list created by David A. Prentice, an employee of the Family Research Council who advises U.S. Senator Sam Brownback (R-KS) and other opponents of ES cell research (1).

Prentice has said, "Adult stem cells have now helped patients with at least 65 different human diseases. It's real help for real patients" (2). On 4 May, Senator Brownback stated, "I ask unanimous consent to have printed in the Record the listing of 69 different human illnesses being treated by adult and cord blood stem cells" (3).

In fact, adult stem cell treatments fully tested in all required phases of clinical trials and approved by the U.S. Food and Drug Administration are available to treat only nine of the conditions on the Prentice list, not 65 [or 72 (4)]. In particular, allogeneic stem cell therapy has proven useful in treating hematological malignancies and in ameliorating the side effects of chemotherapy and radiation. Contrary to what Prentice implies, however, most of his cited treatments remain unproven and await clinical validation. Other claims, such as those for Parkinson's or spinal cord injury, are simply untenable.

And here's the references that are noted,
1. Posted at the Web site of DoNoHarm, The Coalition of Americans for Research Ethics (accessed 8 May 2006 at www.stemcellresearch.org/facts/treatments.htm).
2. D. Prentice, Christianity Today 49 (no. 10), 71 (17 Oct. 2005) (accessed 8 May 2006 at www.christianitytoday.com/ct/2005/010/24.71.html).
3. S. Brownback, "Stem cells," Congressional Record, 4 May 2006 (Senate) (page S4005-S4006) (accessed 8 May 2006 at http://frwebgate6.access.gpo.gov/cgi-bin/wais-gate.cgi?WAISdocID=122359256098+2+2+0&WAISaction=retrieve).
4. According the latest version of the list, accessed 12 July 2006.

Human Reproduction: Definition of Human Embryo

Y'all didn't seriously think a little thing like my husband's left hip surgery would stop me, did you?

Human Reproduction, a peer-reviewed, high impact journal of research and opinion concerning "the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues" (free, full text online in advance of pulishing) has published the following definition of a human embryo:

The following biological definition of ‘human embryo’ is proposed.

A human embryo is a discrete entity that has arisen from either:
(i) the first mitotic division when fertilization of a human oocyte by a human sperm is complete or
(ii) any other process that initiates organized development of a biological entity with a human nuclear genome or
altered human nuclear genome that has the potential to develop up to, or beyond, the stage at which the primitive
streak appears,
and has not yet reached 8 weeks of development since the first mitotic division.

There is "insufficient information whether the entities derived by parthenogenesis, gametogenesis using pronuclear DNA from two parents, and several SCNT and Chimera scenarios which - prior to their creation - have had the ability to implant removed from the genome. However, the entity would be covered by the definition if the manipulation can be said to have "the potential to develop up to, or beyond, the stage at which the primitive streak appears."

I would think that this definition would cover most of the most troublesome aspects involving regenerative medicine or destructive human embryo technique. The uncertain cases would need to be proven to not be human embryos, through animal models, or for the more unethical, actual experiments using human DNA.

Let's hear no more about "early" stem cells, or "there's no sperm(!)" or "there's no potential to form a human baby/person/be implanted in a uterus," etc.

Thank you Human Reproduction, for making this article available free. The tables, showing the need for human oocytes and the sources of DNA and cytoplasmic (oocyte) material necessary for the production of each class, are invaluable.

Same story, new spin

It's (she's) an embryo. What part of "I'm all for stem cell research, but don't kill a human embryo" don't they get?

Harvard's George Q. Daley is in the news again. This time his research group has produced parthenogenetic mouse embryos, that were used to harvest stem cells. The original article has been published online (Free abstract) before going to print, in Science Express, a feature of the journal, Science. Another well-written review from a slightly different is available online at "ThisisLondon.com," a feature of the UK's Evening Standard. Here's another from Scientific American. Frequent mention of "virgin birth" in the articles is telling.

The method used chemical treatments to prompt the egg to develop into an embryo, a process known as parthenogenesis, and then extracted stem cells from it.

The embryo could not have otherwise developed into a baby mouse, so, even in humans, the strategy is unlikely to raise as serious ethical objections as other methods that destroy a viable human embryo.

I don't think so. The only reason that the "embryo could not have otherwise developed into a baby mouse" is because the researchers intended to destroy it in order to harvest those stem cells. If the embryo had been human, the creation of an embryo in such a situation (that carries a high level of risk for the embryo) can not be ethical.

Parthenogenetic mouse embryos have been developed before, as the Boston Globe artical notes. In 2004, an article in Nature (free abstract online) reported that one of these embryos was implanted and grew to birth, grew to adulthood, became pregnant herself and gave birth to normal mouse babies. This was one of 10 who survived nearly to birth of 23 embryos that were implanted.

Why shouldn't we assume that if the hurdles of parthenogenesis in humans is overcome that the problem with implantation and gestation to whatever stage of developement will seem useful to researchers?

At least, this Boston Globe article doesn't use the term "virgin birth" and it is more honest than some mass media stories on cloning and destructive embryonic stem cell production. The author, Cary Goldberg calls the embryos "embryos" and mentions the worries about tumor formation and other abnormalities of stem cells derived from embryomnic stem cells, as well as the risk of tumor production:

The immediate benefit of the technique is for researchers; it still has many hurdles to overcome before it will be clear whether it is safe for use in humans, said George Q. Daley of Children's Hospital Boston, senior author of the paper published online in the journal Science. There is concern, for example, that such cells could become cancerous.

But, he said, the technique may be closer to working in humans than somatic cell nuclear transfer, the conventional approach in animals for generating customized embryonic stem cells.

In that method, a nucleus from a regular cell such as a skin cell is inserted into an egg and induced to develop.

Also known as therapeutic cloning, it is highly inefficient in animals and has yet to be mastered in humans, though two Harvard teams, including Daley's, are trying.

"This is a much more workable approach to generating patient-specific and tissue-matched embryonic stem cells," Daley said. "But the trade-off is that these cells may not prove to be normal and functional."

If the egg technique works in humans, women would be their own immediate beneficiaries, but the effects could be wider, Daley said. It could also lead to the broader production of stem cells that have only half the usual set of immune system genes -- perhaps even whole banks of such cells -- and that therefore would be compatible with many patients who need to grow new tissue.

Professor Daley needs to Google umbilical cord blood cells.

Reports on kidney repair by (ethical) stem cells (and more!)

You may not have read it in the New York Times, but there's exciting news supporting the hope that ethical - non-embryonic - stem cells may be used to treat not only diabetes, but to repair kidney damage.

The most significant article is from The Procedings of the National Academies of Science, which, although largely ignored by the mainstream press, was summarized in a November report in the National Geographic online:

In a study published in November in the journal Proceedings of the National Academy of Sciences, researchers reported that stem cells derived from human bone marrow and transplanted into diabetic mice stimulated the animals' pancreases to produce insulin, repairing damage caused by diabetes.

"This fits with a large body of evidence that these cells have this remarkable ability to go to injured tissues and repair them," said the study's lead author, Darwin Prockop, the director of the Center for Gene Therapy at the Tulane University Health Sciences Center in New Orleans, Louisiana.

In the future, Prockop said, "the therapeutic idea would be to take small amounts of marrow from patients, then grow a large number of these cells, and give them back to the same patient to heal tissue."

From The Procedings of the National Academies of Science article:

The observations here do not rigorously rule out the possibility that the improvements in the glomeruli were secondary to the lower blood glucose levels in the treated diabetic mice. However, it was striking that the human cells were found exclusively in the glomeruli and that some the cells apparently differentiated into endothelial cells. Therefore, the simplest interpretation of the data are that the engrafted hMSCs either prevented the pathological changes in the glomeruli or enhanced their regeneration.

Support for the belief that treatment for kidney damage and disease will come from ethical sources is reinforced by a report from this week's 48th Annual Meeting of the American Society of Hematology (ASH(TM)). Hematologists are the specialists in treating blood disorders, but their field overlaps with Oncologists in the treatment of cancers and, because of the work with bone marrow stem cell transplants, many are also involved in stem cell research.

Three of the papers presented at the ASH conference were on ethical stem cells, including one that dealt with damage from Graft vs. Host Disease in transplant patients using bone marrow stem cells, treatment for one type of "SCID" (popularly known as "bubble boy syndrome," a genetic defect that causes an almost total lack of ability to fight off infection) and the one dealing with stem cell treatment for kidney failure.

As if these two sources were not enough evidence there's a research article in The Journal of the American Society of Nephrology (free abstract) that reports on the isolation of stem cells from the kidneys, themselves.


These reports are exciting news - and should have received much more media coverage - due to the shear numbers of patients who experience acute and chronic renal or kidney failure and disease due to infections, drug reactions, high blood pressure, heart disease and diabetes.

Fetal vs. umbilical cord neural stem cells

The news about "Stem Cells, Inc.'s" phase I trials of fetal neural stem cells in the treatment of Batten disease reports improvement in the condition of the first patient.

I'm a little shocked at how matter-of-fact the article treats the use of brain cells from aborted infants.

Why is there not more questioning about the process and methods involved in harvesting these cells? Where is the open scientific communication?

And why, in the reports about this trial, are there no discussion about - seemingly no consideration of - ethical stem cells from umbilical cords and adult tissues?

Of course, there have never been any human trials using embryonic stem cells. The tissues transplanted into Daniel Kerner's brain are fetal stem cells - the babies killed in the abortions before their brains were collected and then processed for the transplant were at least 8 weeks along, and probably a bit more. However, there's not much info on the "purification" process that resulted in the volume of "purified neural stem cells."

There is quite a bit of research showing that neural stem cells are available from the cells harvested from umbilical cords and even adult sources, such as bone marrow and neural tissue in the mature body.

Wharton's jelly cells have been "easily" ( Free abstract online) induced to transform into neural stem cells and to proliferate in the lab - at least 80 doublings. In animal models, the cells are being evaluated for use in treating Parkinson's and other neurological disease.

There are also reports of development of stem cell lines from bone marrow cells, brain, and even skin cells.


Perhaps, now that "Stem Cells, Inc." researchers believe that they know the specific markers that are to be found on the cells they believe to be useful, they can turn their efforts to more ethical research. And more accessible stem cell sources, especially umbilical cord cells. Even with 1 out of 3 babies aborted in this country, most are aborted at the embryonic stage (1st trimester), and so there are many, many more opportunities to harvest ethical stem cells from umbilical cords.

ASBH day 2: Human rights and Public Health Ethics

Ever been the only conservative in the room? I can go one better: a woman from Rhode Island responded to my confession that I'm a conservative by saying that we should talk, since she'd never had a conversation with a conservative before and she wanted to understand how we think.

BTW, before I go on, I need help: I was told by one of the speakers that some proponents of human dignity defend the "dignity" of "stem cells" in the same way that they defend the dignity of "the impaired." Supposedly, in the discussion about the ethics of research on human tissue banking, some focus on the dignity of the tissue as separate from the infringement on the dignity of the original donor of the tissue. She could not give me a reference, but seems a bright young woman, so I wonder if anyone can explain where this idea could come from.


I guess I ought to explain how the conference is set up. Most of the day, there are 1 to 1 1/2 hour sessions with 5 or 6 different groups, consisting of 2 or 3 (up to 5) panelists who present a paper (or summarize a paper, if time seems short) on a given theme. The presentations are followed by a question and answer period. There's never enough time for the Q and A, so I end up asking my questions after the conference.

Today, I attended sessions on "Bioethics and Public Health Ethics" and "Human Rights and Human Dignity: Curb your enthusiasm." Each of the sessions touched on the basic idea of human rights. And each seemed to get the most bang out of political points: the Bush administration is abusive and against the bioethics Powers That Be.

In the first, we were asked to consider the proposition that Public Health Ethics should be more concerned with the good of the community, rather than attentive to individual rights. After all, public health and most health care systems are public, community enterprises, and an activity of the State that relies on pooled resources and interdependence.

However, aren't Law and the Court system activities of the State, based on pooled resources and interdependence? And aren't these systems still governed by the fact that the rights of the individual are primary?

We also heard how inept the Bush administration was proved to be in the Katrina/Rita hurricane "debacle," although the panelist later stated that the basic problem was the failure to repair the levies and protect the people in the way of the flood. Somehow, the panelists believe that all political failures in public health policy began in 2001. There was no mention about the debacle that came from the redefinition of oral sex as not being "sex," for instance.

The second session was based on the deconstruction of a single term, "human dignity," and a rather confused discussion about human rights. In both cases, the presenters seem to believe that the Bush administration is responsible for attempting to foist an idea of the inalienable rights of human individuals.

Like Caulfield and Brown in this article, the presenters object to protection of human embryos and the children of the future as bearers of human dignity because the concept is not held by all and will not stand in a pluralistic society.

An interesting twist was the first presenter's statement that the proponents of human dignity include "stem cells." (see above)

Beliefs about which members of the human species are bearers of rights are not consistent throughout the world. Islamic nations do not hold that women bear full human rights: women are not protected from killing, enslavement, and are not allowed freedom of movement or ownership of property.

However, regardless of a lack of consensus, or more particularly in the case of disagreement, hasn't history shown that it is it better to support the wider classification of human rights in the case of all races, both sexes, all religious and political backgrounds?

The fact that some of the "dignitarians" and human rightists have expressed concern about the humanity of our descendents who are no longer members of our species was mentioned. I believe that this concern will complicate our efforts to protect the (negative) right to life.

Believers who hold that humans are created in the image of God base our argument for human dignity on our duty to Him for giving us life. If we are created, it's obvious that we and our children are not here because of our plan and efforts, but because of His. Those of us who are concerned about whether or not our children who are not of the human species are 'human" would do well to spend some time contemplating whether or not it is possible to divide the image of God.

Edited for typos at 11:30 PM CDT

85% Type 2 diabetics treated with ethical stem cells

http://www.medicalnewstoday.com/medicalnews.php?newsid=37226

Here's an article (from a reliable medical site, despite the typos and obviously poor translation from the original) on bone marrow cells taken from the patient and used to treat diabetes by injecting the appropriate stem cells into the pancreas. 85% of 16 - that sounds like 14 of the 16 began making their own insulin, C-peptide, etc. --- in other words, their beta islet cells were improved somehow.

From animal models, we have reason to believe that the patient's existing beta cells in the islet of the pancreas were supported and encouraged to divide, rather than the stem cells from the bone marrow differentiating to become islet cells. But, the jury's still out.

The article says this is the most significant advance since the discovery of insulin in 1929.

A side issue ---

The paper concerning this research was presented in December to the American Society for Cell Biology. The Press Book can be accessed here.

Every day, I read of stories such as this one, concerning treatments reported at legitimate medical meetings, without a peep in the mainstream media. There's definitely not the same level of hoopla that Hwang and the puppy-cloning team got.

Over 80% of Type 2 diabetics? and no major media blitz??

Edit, December 6, 2006
As noted in the comments, below, there is no follow up on this article, and no corroborating evidence on line or on a Pub Med search. The American Society of Cell Biology "Press Books" have a new url, here. There is no mention of the presentation in the Press Book. Please see the post from today (December 6, 2006) with some relevant links to research in animal models.