The Stem Cell Debate Heats Up

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

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

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

And no one has to die for it.

Human-pig embryo approved in UK

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

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

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

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

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

New York Times article on cloned humans

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

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

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

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

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

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

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

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

The media will have fun with this story.

Human embryos cloned in California

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

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

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

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

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

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

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

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

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

Myths on Myths about stem cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

Red florescent cat cloned

In my day - we just belled them. Poor kitties won't be able to catch mice. The author reminds us about the veterinarian fake cloner, Hwang Wu Suk, before he finishes.

From the Korean Times:

Researchers found a way to clone pet cats five years ago. Now they can play a trick on their genes to change their color.

A Gyeongsang National University team said they have succeeded in cloning cats after modifying a gene to change their skin color. Because of the red fluorescence protein in their skin cells, the three Turkish Angola kittens look reddish under ultraviolet light, the researchers said.

The red cloned cat research is expected to be utilized in dealing with certain genetic diseases in animals and humans. It will also help reproduce rare animals, such as tigers and wildcats, which are on the verge of extinction, the team said.

According to the team led by professor Kong Il-keun, four kittens were born in January and February by caesarian section, but one died during the procedure. They weighed between 110 and 136 grams at birth and now weigh 3.5 kilograms each now, the researchers said.

``We have proved our world-class ability in cloning animals that have modified characteristics,'' said Kong. ``We found that the red fluorescent protein in all the organs of the dead kitten, which means we have established an efficient way of cloning gene-modified cats.''

The first cloned cat, nicknamed Copycat, was born in 2002 at Texas A&M University. Many other animals such as cows, dogs, pigs, bulls and goats have been successfully cloned by a number of researchers in North America, Europe and South Korea.

Kong cloned a cat in 2004 for the first time in the country. He has since worked as director of research at a state-supported project to clone animals for therapeutic research.

To clone the Turkish Angola cats, Kong's team used skin cells of the mother cat. They modified its genes to make them fluorescent by using a virus, which was transplanted into the ova. The ova were then implanted into the womb of the donor cat.

Called reproductive cloning, the method has been mostly used in cloning animals that are genetically identical, until Kong's kittens were born with the tampered genes.

The technique differs from therapeutic cloning, which is to make a ``stem cell'' that can be guided to grow into a specific body part. Former Seoul National University professor Hwang Woo-suk used this method in his human stem cell cloning research, which was later found to have used fabricated data.

Lee Silver: iPCs named due to politics

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


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

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

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

From the thread following the interview:

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

. . .

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

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

Hat Tip to The Daily Transcript at ScienceBlogs.

New Stem Cells Questions and Answers

A reader posts some questions that I'll try to answer. (Thanks, Janet!)

The most important thing to remember is that the new iPS cells appear to be like embryonic stem cells, but they can be made without killing anyone and they can be made to match the patient.


"Does this new procedure use any cells from the unborn to induce pluripotency in the adult skin cell thus creating a stem cell?"

Both labs in the news actually showed their final process using adult cells that did not require the death of any human individual at any age.

However, one of the groups (Thomson's, from Wisconsin) proved that the process is possible by using embryonic stem cells and fetal cells from abortions, while the other group (Yamanaka's, from Japan) used mouse cells for the basic science before using adult skin cells.

"If it does, then it cannot be considered an ADULT stem cell. So, it seems there would need be a third category of stem cells.

"If it does not use cells from the unborn, then could the iPS be considered an ADULT stem cell? It would be simpler to explain. Or because it is not a stem cell to begin with but is induced to become an ADULT stem cell, do we still need a third category for stem cells.

"I think that if the cells that are reprogrammed came from tissues after birth, they are adult stem cells, and the research using them is "adult stem cell research." (or non-destructive stem cell research resulting in induced pluripotent stem cells.)"

It can get complicated, and you do have to read "the fine print" in the reports to figure out the source.

I've always thought of the two groups as divided into

1. Destructive Research - that depends on the intentional destruction of individual human beings at any age is unethical vs.
2. Non-destructive Research - ethical research methods that do not intentionially cause injury to human beings.

For simplicity, most people call the first "embryonic" and the others "adult."

For instance, umbilical and amniotic fluid cells are ethical, non-destructive stem cells that are technically "fetal stem cells."

In contrast,
1. "embryonic" means the cells came from embryos - in humans that's up to 8 weeks gestation.

2. Most of the "fetal cells" used in research come from harvesting the bodies of children who are aborted, between the age of 8 weeks and term. These are sold as tissue cultures by commercial labs. Some of the cultures have been cultivated for 20 or 30 years and the genes and growth habits have been studied and they can be counted on to do what they are supposed to do.

3. Sometimes the "fetal" tissues are harvested after a natural miscarriage. These are considered ethical. (I don't think there are any commercially available standard tissue cultures from miscarriages.)

"I realize this is very basic and elementary to the posts that you get from doctors and other scientists but I believe that we must have clear definitions BASED ACCORDING TO WHERE THE STEM CELLS COME FROM to educate the voter and to keep the issues clear so that legislation isn't passed to support this new procedure with wording that would allow funding to inadvertently go to human embryonic stem cell research and human cloning."

Usually name is based on where the cells came from, but if the cells acted like the very early embryo - if they were truly "totipotent" like the zygote which is able to make both the body and the placenta - then research on them would be unethical.

The problem with "therapeutic" cloning, for instance, is that it would create a new human embryo that is capable of self-directed, organized development.

Even if he or she will be killed or die naturally in a few days, it's not right to create human beings with the intention of destroying them or using them for the benefit of others and to their own harm.

"Irregardless of the media and the bloggers who support human embryonic stem cell research and human cloning, most Americans do not believe in the Communist philosophy that the end justifies the means. No matter what our vocation or business, we draw the line when the means are immoral. We expect other Americans to do the same, including scientists and researchers. Destroying one human being to help another is clearly immoral and we should not have to fund it. We will vote accordingly."

I agree. We believe that "self-" should always be part of "sacrifice."

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 ---

Dolly's Dad: Cloning, embryos and eggs not needed

10 years after the world learned about the cloning of Dolly the sheep, the scientist responsible for her birth announces that cloning is passe'.

Just after the announcement that a US lab has managed the first confirmed cloning of primate (monkeys, not human) embryos using adult cell donor DNA, Ian Wilmut made statements to the UK press that he's abandoning the cloning track for research using something like Japan's Yamanaka's process of dedifferentiation or reprogrammed adult cells to produce stem cells. (He's also selling the paperback version of his latest book.)

This approach, he says, represents, the future for stem cell research, rather than the nuclear transfer method that his large team used more than a decade ago at the Roslin Institute, near Edinburgh, to create Dolly.

Last year, at the American Society of Bioethics and Humanities Conference, the top ‘ethicists’ were nearly in a panic over these techniques. They evidently put pressure on Yamanaka to and criticize his own research. Then, 3 other labs proofed the technique and the Yamanaka’s lab advanced a step or two. Gearhart and Moreno were still scoffing last month, when they spoke at the National Academies of Sciences museum during the ASBH conference.


I’m afraid that too many labs and too many PhD candidates and sponsors have all their eggs in the cloning basket for the issue to fade decently. Talk about being left behind — all US research centers, such as the California Institute of Regenerative Medicine — will be negated if they insist on following the dead end trail of cloning and unethical destructive embryonic stem cell research.

The Yamanaka technique involves reprogramming adult fibroblasts - skin precursors - to a primitive, embryonic stem cell state. The stem cells are not quite 'totipotent" from what we can tell -- they aren't capable of forming new embryos. But they are capable of forming "all the cells of the body," at least with manipulation in the proper environment.

We're going to hear more and more dispute about the "proper" name for the cells -- disputes over whether they are actually stem cells. And a huge amount of discussion about the dangers from the viral transfection that is used to add the genes that turn on stemness.


We will be expected to forget that

1. No one has been able to clone a human embryo in spite of thousands of eggs used in Hwang's scam alone,

2. That 13,000 monkey eggs were used in the latest attempt to clone primates, that the published study relates an efficiency of 0.7% success, and the authors aren't quite sure why they were successful where other labs weren't,

3. The fact that true embryonic stem cells are short lived in the body and difficult to control (reports actually criticized the embryonic like stem cells from dedifferentiation for making tumors in mice - although that is one of the properties that defines embryonic stem cells)

4. That transfection with plasmids and specialized virus particles is an established technique of gene therapy,

5. and that the production of stem cell lines toward the end-stage adult cells has used viral transfection as well.

Even though he spouts the proper mumbo jumbo about the "moral status of the human embryo" (and that a person is someone capable of valuing herself - with the gradual acquisition and loss connected with functional capability), don't be surprised if Wilmut is, himself, negated and Watsoned because of his disloyalty to the cloning and embryo-destructive catechism. (James Watson's non-PC comments from last month cost him his lab, although he's been saying the same things for years.)


Now, if only the US, and especially the Texas, research Powers That Be will pay attention and learn.

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.

Bioethics on the Ballot

Texas approved Billions in bond debt, some $3 Billion of which will fund the new Cancer Prevention and Research Institute of Texas. There is already private funding of embryonic and fetal tissue research in Texas already.(See this report on the Brown Institute in Houston.) While Texas is a leader in ethical stem cell research and public cord blood banking, there are no limits on State tax funds for research that would limit any sort of destructive research on unborn humans, including cloning, embryonic stem cell research and fetal research. As long as none of the subjects are able to hire a lawyer, it's open season in Texas. The prolife community in Texas is hoping - and has already begun the fight - to ensure that the oversight board will be able to control the use of the money for ethical means.

New Jersey, on the other hand, rejected funding for embryonic stem cells! Hooray!

First babies from "Lab Grown Eggs"

Well, the news out of Great Britain that apparently healthy twins were born from a new technique involving maturation of human oocytes - "eggs" - outside of the body will probably be hailed as the solution to the problem of where to get the eggs for embryonic stem cell and cloning research. It won't solve the problem that I asked earlier today as to whether and why it's important or ethical.

It's interesting that the article emphasizes the danger of Ovarian Hyperstimulation Syndrome:

In mild and moderate cases, affecting up to 20% of women undergoing ovary stimulation, this leads to symptoms such as swelling and breathlessness that resolves.

However, in about 1% the symptoms can become so severe that they are deadly. Among women with PCOS [Polycystic Ovarian Syndrome], the rate is nearer 5-10%.

Thanks to Wired Science blog for the tip.

Hwang "blew it"

From Fowler's Health and Science Update comes another lesson in hubris and the old saying about tangled webs and deception:

Disgraced Korean Cloner Blew It: He Did Make History
A new report by a team of US researchers says the human embryonic stem cells generated in a now-discredited experiment in South Korea, actually were a first. When Woo Suk Hwang announced three years ago he had created the first human patient-specific ESC, he was hailed as a science hero.

He said he did it with a cloning technique called somatic cell nuclear transfer, a tricky process in which a nucleus is inserted into a cell. Last year he and other researchers were fired after it turned out they fabricated data. But now, Harvard scientists say analysis of Hwang’s embryos show they were in fact the first-ever human cells created by parthenogenesis, virgin birth. The multiplying cells were the result of an egg alone.

The kicker is the Korean team had apparently hit upon a technique that scientists say could have resulted in a major advance for stem cell research, and were years ahead of anyone else. Had they been truthful, Hwang and colleagues might still be heroes, and embryonic stem cell therapies would be that much closer to reality.

IVF embryo donation for destruction

I've had some time to consider the report that we read last week concerning the willingness of the women and men who control the fates of the frozen embryos of their children to donate those embryos for destruction in research. The report has been published in ScienceXpress, the early posting on line of articles before they appear in print in Science Magazine. Unfortunately, it's behind a "pay wall." However, you can read the "Supporting Online Material" and see most of the report as well as the actual questions, without a subscription - or at least without being signed in.

Please note the use of words such as "assume," "likely" (twice in one assumption), "if," and the use of "somewhat likely" as equivalent to "very likely."

Since it appears to be okay to make assumptions about this subject, I have a few of my own.

I assume that anyone who has entered into in vitro fertilization and agreed to have their embryonic offspring frozen has already come to grips with the possibility that some of these embryos will be killed in the process. Those who have moral problems with the destruction of their embryos would not be as likely to have frozen, stored, "supernumary embryos" in the first place.

Furthermore, the data does result from self-reporting about theoretical intentions, which is not as reliable as actual actions.

I would like to see the answers of the 40% of women (egg donor/mothers) and the 49% of partners (men and women) who did not return the questionnaire. (Actually, that's 35% and 44% who received at least one copy of the questionnaire, who did not return it.)

I would also like to see the answers about the intentions of those respondents who did not have any embryos in frozen storage, as well as the answer to one more question: "Why haven't you donated your embryos?"

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.

Non-destructive embryonic stem cells

It's all over the web (here and here, at the "news@nature.com" site,for instance), three separate labs have been able to reproduce embryonic stem cells by "reprogramming" adult cells from skin.

Much of the commentary is like Art Caplan's comments quoted in the first (Blog.bioethics.net) link above. Paraphrased, the bulk of the "mainstream remarks include, "It's only in mice, and they had to used viral vectors." Well, if you will look at all the much-hyped embryonic "break-throughs," you will see that they are "only in mice" and many of them "used viral vectors."


Caplan, who notes the coincidental timing with legislation in Washington and who chronically sees bioethics through a political lens, couldn't pass up the chance for a rant on "embryos are not people." When I was an embryo, it was close enough for me - and my Mama. I actually agree with Art Caplan's comment that ". . . ditching embryos and jumping to fund alternatives is not the right response to this fascinating news about mouse cells." The reason we won't fund embryonic stem cell research requiring the distruction of human embryos is not because we have an alternative source. It's because we won't fund research that depends on the destruction of embryonic humans.

The abstracts for two of the articles are published on the Nature advance publication online page. (I don't yet have access to the third, in Cell's Stem Cell journal.

Nature advance online publication 6 June 2007 | doi:10.1038/nature05934; Received 6 February 2007; Accepted 22 May 2007; Published online 6 June 2007

Generation of germline-competent induced pluripotent stem cells
Keisuke Okita1, Tomoko Ichisaka1,2 & Shinya Yamanaka1,2
1. Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
2. CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
Correspondence to: Shinya Yamanaka1,2 Correspondence and requests for materials should be addressed to S.Y. (Email: yamanaka@frontier.kyoto-u.ac.jp).

We have previously shown that pluripotent stem cells can be induced from mouse fibroblasts by retroviral introduction of Oct3/4 (also called Pou5f1), Sox2, c-Myc and Klf4, and subsequent selection for Fbx15 (also called Fbxo15) expression. These induced pluripotent stem (iPS) cells (hereafter called Fbx15 iPS cells) are similar to embryonic stem (ES) cells in morphology, proliferation and teratoma formation; however, they are different with regards to gene expression and DNA methylation patterns, and fail to produce adult chimaeras. Here we show that selection for Nanog expression results in germline-competent iPS cells with increased ES-cell-like gene expression and DNA methylation patterns compared with Fbx15 iPS cells. The four transgenes (Oct3/4, Sox2, c-myc and Klf4) were strongly silenced in Nanog iPS cells. We obtained adult chimaeras from seven Nanog iPS cell clones, with one clone being transmitted through the germ line to the next generation. Approximately 20% of the offspring developed tumours attributable to reactivation of the c-myc transgene. Thus, iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.
Although ES cells are promising donor sources in cell transplantation therapies1, they face immune rejection after transplantation and there are ethical issues regarding the usage of human embryos. These concerns may be overcome if pluripotent stem cells can be directly derived from patients' somatic cells2. We have previously shown that iPS cells can be generated from mouse fibroblasts by retrovirus-mediated introduction of four transcription factors (Oct3/4 (refs 3, 4), Sox2 (ref. 5), c-Myc (ref. 6) and Klf4 (ref. 7)) and by selection for Fbx15 expression8. Fbx15 iPS cells, however, have different gene expression and DNA methylation patterns compared with ES cells and do not contribute to adult chimaeras. We proposed that the incomplete reprogramming might be due to the selection for Fbx15 expression, and that by using better selection markers, we might be able to generate more ES-cell-like iPS cells. We decided to use Nanog as a candidate of such markers.
Although both Fbx15 and Nanog are targets of Oct3/4 and Sox2 (refs 9–11), Nanog is more tightly associated with pluripotency. In contrast to Fbx15-null mice and ES cells that barely show abnormal phenotypes9, disruption of Nanog in mice results in loss of the pluripotent epiblast12. Nanog-null ES cells can be established, but they tend to differentiate spontaneously12. Forced expression of Nanog renders ES cells independent of leukaemia inhibitory factor (LIF) for self-renewal12, 13 and confers increased reprogramming efficiency after fusion with somatic cells14. These results prompted us to propose that if we use Nanog as a selection marker, we might be able to obtain iPS cells displaying a greater similarity to ES cells.

and

Article Nature advance online publication 6 June 2007 | doi:10.1038/nature05944; Received 27 February 2007; Accepted 22 May 2007; Published online 6 June 2007

In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state

Marius Wernig1,6, Alexander Meissner1,6, Ruth Foreman1,2,6, Tobias Brambrink1,6, Manching Ku3,6, Konrad Hochedlinger1,7, Bradley E. Bernstein3,4,5 & Rudolf Jaenisch1,2
1. Whitehead Institute for Biomedical Research and,
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
3. Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
4. Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
5. Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
6. These authors contributed equally to this work.
7. Present address: Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Harvard Medical School and Harvard Stem Cell Institute, Boston, Massachusetts 02414, USA.
Correspondence to: Rudolf Jaenisch1,2 Correspondence and requests for materials should be addressed to R.J. (Email: jaenisch@wi.mit.edu).

Nuclear transplantation can reprogramme a somatic genome back into an embryonic epigenetic state, and the reprogrammed nucleus can create a cloned animal or produce pluripotent embryonic stem cells. One potential use of the nuclear cloning approach is the derivation of 'customized' embryonic stem (ES) cells for patient-specific cell treatment, but technical and ethical considerations impede the therapeutic application of this technology. Reprogramming of fibroblasts to a pluripotent state can be induced in vitro through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cells—derived from mouse fibroblasts—can form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.

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.

"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."