Texas Legislators Seek to Limit Funds for Human Embryo Destruction

Senator Steve Ogden is a Texas Hero!

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

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

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

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

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

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

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

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

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

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

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

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

See my Update, written after I read the report.

"Tea-bag" Adult Stem Cell Treatment for Stroke

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

"Fertilized eggs" and cloned human embryos (The future, again)

"ScienceBlogs" is one of the examples I give when I'm trying to explain the anti-life, anti-religion atmosphere that is pushed (like a religion itself) in our universities and by the Powers That Be in science academia and publishing. I think I may have identified one or two of the bloggers as believers (proof that miracles happen?), but no one identifies as pro-life or even respectful of us.

Normally, the community in the 66 blogs over at "ScienceBlogs" talk to each other, but I read them to see what's going on. Since I have a tendency to tilt at windmills, occasionally I post. The gang over there is so unhappy with the breakthrough on embryonic like stem cells from adult stem cells that it's almost like reading up on the Clintons at one of the Pink or websites. (Watch out for the language.)

I posted a reply to the atheist blogger (look for the "Red A" banner suggested by Richard Dawkins), PZMyers, who wrote some silliness at his blog, "Pharyngula" today. (I ignored the nonsensical non sequitur that the President hadn't shown any interest in alternative fuel - I can remember months of jokes about the saw grass and there's a Kennedy blocking the wind farms on the East Coast, for Pete's sake.) But I did point out that there's been no impediment (other than in the funding of Ph.D. candidates who moan about staying up 'till 2 AM - standard for pre-meds and interns in the old days) because of the Bush administration policy on stem cell research.

One poster replied with 500 words to convince me that "fertilized eggs" do not have any moral standing, cloned human embryos would not be cloned humans and that reprogrammed, mesenchymal or any of the other ethical stem cells do not have the promise that embryonic stem cells do. Along with the problem of how long it takes to direct embryonic stem cells.

First, an egg ceases to be an egg when it's fertilized. At that point, it's an embryo.

Second, the poster is not keeping up. The mainstream press and science publishers no longer argue that somatic cell nuclear transfer doesn't result in an cloned embryonic primate or human.

Third, again, you've got to keep up: James Thomson has said that the reprogrammed cells, "are probably more clinically relevant than embryonic stem cells," he explains. "Immune rejection should not be a problem using these cells.""

In the near future, the treatments will come from stem cells and precursor cells - it probably won't be necessary to start at the embryonic stem cell or pluripotent stem cell stage. While each line of multipotent adult stem cells is more limited than the ideal embryonic stem cell line, there are many kinds of multipotent lines. I expect the lessons we learn from the Yamanaka and Thomson techniques to be used to begin at these more differentiated cells, which can be directed faster and easier than the pluripotent cells, with their innate pathonemnonic tendency to form tumors.

In the long run, we hope to prove John Gearhart right: he's been on record for 5 (Washington Fax, November, 2002) years that, "Stem cells won't be used as therapies, but will spawn them."

Just as we use stimulating factors to encourage the production of blood cells, rather than transfusing as often as we once did, the plan is to learn to turn the necessary genes on to produce the specific transcription factors that will stimulate stem cells. We'll learn about "tropic factors" like the brain-derived neurotropic factor that seems to regulate the development of nerve cells and nerve repair.


5 years ago, we hadn't found all the stem cells and precursors that we know about, now. We didn't realize that women continue to make oocytes after birth, that there are neuron stem cells and precursors, that we can make functional liver tissue masses from umbilical cord blood. We certainly didn't know as much as we do - and how little we know - about Oct4 and the other regulatory homeodomains. We didn't understand about niches and the vital role of the physical environment and conditions beyond those chemicals.

The poster does use one of my favorite phrases, however: "We stand on the shoulders of giants." He forgets that that will be true for our children of the future, also.

Translating Thomson’s “Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells”

Yu, Thomson, and all, from Wisconsin published their paper on reprogrammed induced Pluripotent Stem (iPS) cells from adult cells online in Science Express online, yesterday, just after the Yamanaka/Takahashi team from Japan published theirs in the journal, Cell. (The Thomson paper was not scheduled to go live online until the 22nd.)

As discussed on this blog, yesterday, Yamanaka’s group built on their earlier research published in 2006 and 2007, using mouse fibroblasts to prove that four genes, Oct4, Sox2, c-myc, and Klf4, could reprogram those cells to a state that resembled embryonic stem cells in all tests that they tried. Then, they used fibroblasts from commercially available samples from 1) a skin biopsy taken from the face of a 36 year-old Caucasian woman, 2) synovial cells (joint lining) from a 69 year old Caucasian male, and 3) neonate foreskin skin fibroblasts.

(This last is a common source of skin fibroblasts, with easily and ethically accessed skin tissue, collected at the circumcision of newborn boys.)

The Thomson team did not begin the basic research using mouse cells and did not simply go forward using the genes from the earlier experiments on mouse cells. Instead, they started at the beginning, using human Embryonic Stem Cells (hESC) that had been directed to become a special type of white blood cell, CD45+. This type of cell can be manipulated to demonstrate whether they had the functioning gene, Oct4 (a definite marker that is used to prove whether or not a cell is a hESC), by growing them in the presence of gentamycin, an antibacterial.

By adding some genes and removing others, the team determined that they had, “identified a core set of 4 genes, OCT4, SOX2, NANOG, and LIN28, that were capable of reprogramming human ES cell-derived somatic cells.” They also discovered that the cells could be reprogrammed into embryonic-like cells without Nanog, but that Nanog made it possible to recover more reprogrammed cells.

(From the text accompanying Fig.1: "In three independent experiments using different preparations of
mesenchymal cells, individual removal of either OCT4 or SOX2 from reprogramming combinations eliminated the appearance of reprogrammed clones, whereas the individual removal of either NANOG or LIN28 reduced the number of reprogrammed clones, but did not eliminate such clones entirely.")

Next, they tested this combination of genes in a commercially available, genetically modified cell culture, IMR90 fetal fibroblasts. (These cells were cultured from a little girl aborted at 16 weeks gestation. ) These cells are fetal cells, not adult cells, and they were chosen because they have been studied and the genome is well known. They do not grow well in the fluids and conditions that encourage cultures of hESCs and the researchers could identify them by the way that they look.

Next, in order to prove that the genes could reprogram “adult cells,” the team used fibroblast cultures from foreskins to produce 4 different cultures of reprogrammed induced Pluripotent Stem Cells.

The authors conclude,

"The human iPS cells described here meet the defining criteria we originally proposed for human ES cells, with the significant exception that the iPS cells are not derived from embryos. Similar to human ES cells, human iPS cells should prove useful for studying the development and function of human tissues, for discovering and testing new drugs, and for transplantation medicine."

Edited typos 11/21/07 17:30 PM (That could be the next neuroscience break through: why don't we see our typos until later?)