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.

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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.
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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.