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.

Changing the rules of biology?

Kelly Hillis, over at the Bioethics.net blog scoffs at the opinion of Concerned Women of America on same sex parenting. She claims that "Science has allowed us to change the rules of biology, and DNA is becoming a tool, not a definition."

I strongly disagree. We can't "change the rules of biology." With quite a bit of effort, we can accommodate to ourselves to work within the rules enough that it appears that we ignore them. While biology isn't destiny, you have to deal with it.

Our very biology is one huge influence toward making emotional commitments to people (and animals and objects, too) that are not close relations. Where do you think the social constructs come from?

I'm a big proponent of acknowledging unconventional families. Especially in our mobile society, we often make "families" of people we love, where we are.

I'd rather add to protections than take away the unique legal protections given the "nuclear family," however. That's still where most of us live, and there's evidence that it's the best environment for children. "Best practices" don't grow out of wishful thinking or great efforts to go around the rules: usual things are usual, and we should only advocate public policy based on findings of a real pattern leading to a desired result.

An interesting designation for experimentation with unconventional families comes from the American College of Pediatricians - a conservative off shoot of the American Academy of Pediatricians. They call it "social eugenics," and don't approve of attempting to "change the rules of biology."

Wall Street Journal on dealing with dying parent

Thank you, Wall Street Journal, for giving us this free article on dealing with a dying family member, focusing on children who live out of town.

The best point: "Just go." You won't regret it.

Virtual science vs. actual experimentation (Emergency Contraception)

There's still no evidence that Plan B interferes with implantation, and lots of evidence that it doesn't.

There have been reports that Drs. Mikolajczyk and Stanford ("Levonorgestrel emergency contraception: a joint analysis of effectiveness and mechanism of action." Fertility and Sterility R. Mikolajczyk, J. Stanford, access to free abstract available, here) have proven that there is an abortifacient effect from the morning after pill ("Emergency Contraception," EC, or the levonorgestrel-only pill protocol, LNG EC).

In fact, they do not "prove" anything. Mikolajczyk and Stanford derived an equation from actual results from observing oocyte follicle development and ovulation in women. They then used statistical, "virtual" models,to estimate they effects of LNG:

We simulated random samples of 10,000 women presenting for EC for a single cycle each, and we calculated the number of ‘‘expected’’ pregnancies for each simulated cohort of women using both sets of the daily fecundity data. We assumed that women ‘‘presented’’ for EC treatment with equal probability on days –10 to +5 around the day of ovulation
(day 0).

For each of the women within the fecundity window, we used the follicular growth equation to estimate a follicular diameter, which in turn was used to estimate the disruption of ovulation by LNG EC based on the data from the Croxatto study (Table 1). We assumed that effects observed for 12–14 mm, 15–17 mm, and R18 mm groups reported by Croxatto et al. (15) apply to follicles of size up 11.51–14.5 mm, 14.51–17.5 mm, and R17.51 mm, respectively. When LNG EC was administered on a day when follicular size was below 11.5 mm, we assumed that there was zero probability of pregnancy. These conservative assumptions maximized the possible effects of LNG EC to disrupt ovulation and prevent fertilization.With this information, we estimated the ‘‘observed’’ pregnancies within the simulated cohorts.

Durand and Croxatto's teams studied how LNG EC actually worked in the bodies of real, live women, using biopsies, exams, assays of hormones and serial ultrasounds, as well as animal studies. Mikolajczyk and Stanford actually refer to the Durand study on human women, "On the mechanisms of action of short-term levonorgestrel administration in emergency contraception," (available free on line, here), but say the evidence from biopsies are "mixed."

On the contrary, Durand reported on actual labs, ultrasounds and even biopsy samples from actual observations:

The results were highly consistent with the chronological date of sampling because differences longer than 3 days between the histologic diagnosis and the day of the cycle were not observed. A total of 24 out of 33 biopsies from treated cycles with ovulatory features were studied. The rest were excluded because of insufficient tissue sample (one from Group B and D) or because sampling did not correlate with the cycle day (three from Group A and four from Group D). Table 3 summarizes the morphological findings in Groups B, C, and D. No significant changes were observed between treated and control specimens in any of the studied parameters. No significant differences among groups were observed. Of particular importance was the finding that the predecidual changes as evaluated by the
presence of prominent spiral arteries, which are considered
crucial for implantation [24], were not altered by LNG.

The post ovulatory mechanism is most likely explained by the finding in many studies, including Durands', which have demonstrated a strong effect on mucus thickness and sperm motility from the Levonorgestrel protocol (LNG EC). Practitioners of Natural Family Planning are familiar with this (natural) effect of (natural) post ovulatory rise in progesterone: when the progesterone levels rise after ovulation, the cervical mucus becomes thick and fertility goes down because the sperm can't get to the egg for fertilization. The movement of the oocyte down the fallopian tube is slowed also, because the cilia in the tube are affected. The combination of these two phenomenon explains the increased rate of ectopic pregnancy in women who do become pregnant using levonorgestrel only EC and daily pills.

There are definitely problems with EC. It only works when it works for 4 or 5 days before ovulation and, possibly on the day of ovulation. (The oocyte only lives about 24 hours.) This is the first time that contraceptive pills have been made available to men as well as women. For some reason, women don't use the pill correctly, even when they have them at home. And we have tons of evidence that neither the pregnancy rate nor the abortion rate are affected by making the pill available over the counter. And there's the increased risk of ectopic pregnancy described above.

However, this "study" appears to be statistics used to argue against observations derived from real life medical experiments in order to prove a pre-conceived position.

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.)

Lancet's "Comments" on its WHO expose'

Here's more from The Lancet, an editorial comment discussing why the World Health Organization's opinions matter at all.

Just last week, I had to answer a pro-abortion argument that had used WHO statistics on abortion, the safety of abortion contrasted with carrying a pregnancy to birth (and delivery of a live child) in relation to the Partial Birth Abortion ban ruling by the Supreme Court on one of the American Academy of Family Physicians' e-mail lists.

Housekeeping

I fixed a broken link in that story about Nature Neuroscience's refusal to allow dissent on its editorial pages, or even a rebuttal when the editors attack a scientist for expressing her opinion in another journal. (It seems that extraneous commas interfere with html.)

If you follow the (functioning) link, there are links to all the editorials and articles in question.

WHO(se) life is it anyway? (Or "We meant well")

The Miami Herald (with a HatTip to Drug Wonks) reports on the Lancet's report on the World Health Organization's lack of evidence for its "evidence based" recommendations and guidelines.

I like this part (From the The Miami Herald) the best:

One unnamed WHO director was quoted in the study as saying: "I would have liked to have had more evidence to base recommendations on." Another said: "We never had the evidence base well-documented."

Pang said that, while some guidelines might be suspect and based on just a few expert opinions, others were developed under rigorous study and so were more reliable.

For example, WHO's recent advice on treating bird flu patients was developed under tight scrutiny.

Oxman also noted that WHO had its own quality-control process. When its 1999 guidelines for treating high blood pressure were criticized for, among other things, recommending expensive drugs over cheaper options without proven benefit, the agency issued its "guidelines for writing guidelines," which led to a revision of its advice on hypertension.

"People are well-intended at WHO," Oxman said. "The problem is that good intentions and plausible theories aren't sufficient."

Edited January 27, 2010 to add "WHO" and "World Health Organization" labels.

Bloggers on "Loaded Lanquage"

The blogger, Nick Anthis, a graduate of Texas A&M and a Ph.D student and Rhodes scholar currently studying at Oxford, occasionally posts at his blog, Scientific Activist ("Reporting from the Crossroads of Science and Politics"). On his "About" page he warns us that "enemies of science" should "Beware!"

As part of his campaign against his "enemies," has a post from May 8, 2007 that notes "Loaded Language in Media Coverage of Embryonic Stem Cells." He accuses the New York Times(!) author, Pam Belluck, and her fellow science reporters of being "pawns of the conservative movement."

But not to worry, he gives Ms. Belluck the exact wording he would prefer:

Instead, the author could write that "President Bush objects to the necessity of what he calls the destruction of human embryos" or that "President Bush objects to the use of human embryos."

However, the commenters on the blog don't appreciate any other viewpoint, especially a clarification of whether or not "destruction of embryos" is an accurate description of the process of harvesting embryonic stem cells. That being said, surely they would benefit from hearing from us.

If you have a minute, stop by and say hello to Mr. Anthis and friends at Scientific Activist.

Edit: 05/12/07 - another broken link.

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.

Texas "Futile care debate: Prolonging life or suffering?"

The Houston Chronicle has an unusually good and balanced article on one case in the on-going debate in Texas on the end of life care, originally published May 6th.

The article uses the example of 91 year-old Mrs.Edith Pereira, and the way that her daughter, Zee Klein, made sure that she got the care that Mrs. Klein believed she should have:

Taking action on her own

Zee Klein wasn't about to just let her mother die, no matter what some hospital committee decided. But instead of waging a high-profile fight against the hospital, she decided to get her mother out on her own.

It wasn't going to be easy. For one, Medicare wouldn't cover Pereira's care if she were transferred to Christus St. Joseph, the downtown hospital where a doctor had agreed to take the case. Her coverage for her particular diagnosis already had been exhausted at Memorial Hermann.

Further complicating matters, Pereira's condition was deteriorating fast — by the time the hospital's futility committee ruled, she was in respiratory distress and her kidneys were failing. Doctors wrote in her chart that the discharge was against their advice.

"The patient was unstable," Castriotta said. "Given how sick she was, doctors felt her release would be dangerous."

The moment wasn't lost on Klein.
"She looked like she was in the throes of dying," said Klein, 68, who had previously cared for her late husband when he suffered a stroke and numerous heart attacks. "We didn't know how long she had."

Still, Klein had a plan. She would have her mother transferred back to St. Dominic nursing home for several hours, then taken to St. Joseph's emergency room, where federal law would require she be admitted.

But would she make it? Pereira's condition was so precarious that paramedics gave her oxygen through a respirator and stood ready to take her to a closer emergency room if it looked like she wouldn't survive the drive to St. Joseph.

On the afternoon of June 26, Pereira was discharged from Memorial Hermann and started the journey.

***
`Extremely poor' prognosis

Pereira made it to St. Joseph Hospital, but doctors summed up her prognosis in two words: "extremely poor."

It was understandable. On the day she was admitted, Pereira's problems included pneumonia; sepsis, a potentially fatal blood infection; dangerously high blood sugar; severe dehydration; a urinary-tract infection; kidney failure; and respiratory distress.

Doctors worked diligently over the next 72 hours to stabilize Pereira, giving her antibiotics, putting her on intravenous fluids, balancing out-of-whack electrolytes that were causing the kidney failure.

Pereira improved significantly, and St. Joseph scheduled an ethics committee hearing to consider all the options, which included inserting a gastric feeding tube. Many doctors, like those at Memorial Hermann, thought that the case seemed futile.

But Klein had one thing in her favor. St. Joseph, which since has been sold to Hospital Partners of America, then was a Catholic hospital.

"We follow the U.S. bishops' directive that the presumption be in favor of nutrition and hydration as long as the benefit outweighs the burdens on the patient," said Mike Sullivan, an administrator at Christus Health Gulf Coast, St. Joseph's corporate headquarters before the sale. "At a Catholic hospital, food and water are considered comfort care."

The ethics committee persuaded Klein to put a "do not resuscitate" order on her mother in the event of a cardiac arrest. A week after the meeting, a St. Joseph gastroenterologist inserted the feeding tube.

On Aug. 12 — a month later, finally free of all infections — Pereira returned to St. Dominic nursing home.

On the one hand, there's a lot to be said for the fact that Mrs. Pereira lived another 8 months and was stable for a while. Mrs. Klein spoke about her mother "firing" a nurse when she told her story to the House Public Health Committee meeting last August 9th, while Mrs. Pereira was still in the hospital. (RealPlay Video at about 8:00/12:38 to about 8:20/12:38 on the timeline) On the other hand, Mrs. Pereira was put through a lot of invasive interventions in the hospital, on a ventilator, dialysis, and other treatment for multiple organ failure, with several readmissions to the hospital over the next 8 months for infections. The last was for treatment for respiratory failure, ending with her death in a long term acute care hospital.

I especially like one of the comments from a reader, "KISDteacher," speaking about the care of her own 100 year old grandmother:

When it takes more than God to keep her alive, she made it clear that she doesn't want to keep going.

As I approach the first Mother's Day after my mother's death, I'm glad that she was spared the debates over feeding tubes and resuscitation. And I am so grateful that I was with her when she died and that I can remember rubbing her back and using a straw and spoon to feed her the afternoon of her death.

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)

AMA on Texas Advance Directive (Futile Treatment)

The AMANews magazine, a weekly print newspaper for the members of the American Medical Association, has an article in the May 14 edition, available on line now. The excerpt is free here, but full content is only available to members and paid subscribers. Since LifeEthics readers have been following the progress of the legislation and know about the most recent action in the Senate Health and Human Services Committee, here's the portion that's not available for free:

Texas hospitals have used their state's advance directives law 27 times to withdraw treatment over family objections, said Robert L. Fine, MD, one of the 1999 law's architects.

Supporters of the status quo say the process normally extends far beyond 10 days.

"This law is usually invoked after days, weeks or even months of negotiation with families," said Tom Mayo, a health law professor at Southern Methodist University in Dallas who has helped evaluate more than a dozen medical futility cases on various hospital ethics committees.

Those seeking to abolish the time limit, however, allege that hospitals are most concerned about the estimated $10,000 a day it costs to provide intensive-care unit life support in these cases.

"The current statute, effectively allowing euthanasia with a polite and perfunctory 10-day notice, is misapplied and rips families away from the bedsides of their loved ones," said Bob Deuell, MD, author of a Senate treat-until-transfer bill, in an April letter to The Dallas Morning News. Dr. Deuell did not respond to AMNews' interview requests by deadline.

Bob Kafka, a Texas organizer for Not Dead Yet -- a disability rights group that opposes the advance directives law -- said in a statement that "the ability of a doctor to overrule both the patient and their surrogate in withdrawing life-sustaining treatment is in violation of the principle of patient autonomy."

But physicians argue that their obligation is principally to the terminally ill patient, not the family.

"It can be hard for patients' families to wrap their heads around the dying process," said Hanoch Patt, MD, an Austin, Texas, pediatric cardiologist who has served on hospital ethics committees and testified against the treat-until-transfer legislation. His patients often require invasive procedures if there is any hope for recovery, "but when a treatment can cause only more pain and suffering without any hope of benefit, then we're just prolonging the dying process, and I'm obligated to stop the treatment."
Compromise in the works

As this story went to press in late April, a compromise bill authored by House Public Health Committee Chair Dianne Delisi that would give families 21 days' notice to secure a transfer before the withdrawal of life support gained backing from the Texas Hospital Assn. and the Texas Medical Assn. The bill also would not apply to cases in which the only life support provided is artificial hydration and nutrition.

Such a compromise is not ideal, said Mark Casanova, MD, an internist at Baylor University Medical Center in Dallas.

"Physicians are going to live within the legal confines that we are forced to live within," he said, "but morally and based on medical ethical principles that are centuries old, we don't feel that it's necessarily appropriate. It's just 11 more days of suffering and pain for these patients that will not result in a single saved life."

AMA policy on futile care says hospitals should develop policies on how to handle such cases, refer them to ethics committees, involve families to the greatest extent possible and attempt to negotiate settlements. If the committee sides with the attending physician, the ethical opinion states, the hospital should seek a transfer, and if no transfer can be arranged, care should be withdrawn.

(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.

End of Life Compromise Texas

According to the Houston Chronicle, the Senate Health and Human Services passed a compromise bill to amend the Texas Advance Directive Act to extend the time lines for end of life care when the doctor believes that technological intervention is inappropriate.

The new committee substitute for Senator Dr. Duell's bill 439 was introduced by the Senator himself. It mirrors the current version of Representative Delisi's HB 3747. There will be 7 days notice before the ethics hearing and 21 days before care can be withdrawn or withheld against the surrogate's wishes. I believe that the House Bill will pass the Committee easily.

I'm sure that the Senator and Representative and their staffs have been working hard to come to this point. I know that those of us who have been advocates have put in many hours and much concern and prayer.

Bravo, 80th Texas Legislature!

Do No Harm 101 (Wesley Smith, Catholic Bishops and Futile Care)

Wesley Smith is covering Texas' legislature's debate over our Advance Directive Act. Yesterday, he accused the 24 Bishops of Texas of practicing "Futile Care Theory," which he defines as the decision to limit care by anyone other than a family member or patient. (In other words, here, he says that Terri Schiavo was not a "Futile Care Theory" case.)

Patient autonomy is not the first principle of medicine - that should be non maleficence guiding beneficence over-rides autonomy. "Heal when possible, but first, do no harm."

If you want to get to basics, the right to life means the right not to be killed, not the right to some one else's actions to maintain your life to the standard that you want and as long as you want. The doctor also has the right to life and the right to liberty.

Those rights intersect in medicine with/by a fiduciary duty of the doctor to place the patient's interests above his own and society has agreed that medicine is a good that we will provide for our community.

These interactions have to be guided by a respect for life and health and the medical knowledge and skills of the doctor. The medical knowledge and skills are the element that is measurable, licensed and verifiable by observers outside the patient-physician relationship. The practice of applying medical knowledge and skills requires medical judgment. Acquiring medical judgment - even if it's just the ability to understand statistics and not a growth of our actual wisdom - is how we learn to do surgery and chemotherapy when it's obvious that there's at least a short term harm.


I certainly don't practice medicine at what Wesley Smith has called "at the macro level." The closest I come to "macro level" thinking is that extra ankle xray to rule out fracture and ward off lawsuits. And I don't dare touch a pregnant woman after 20 weeks without all kinds of informed consent forms that ensures we understand that I'm taking care of the cold or sprained ankle (no xray here, without the Obstetrician's permission), because I'm not insured for OB care.

Nevertheless, money is a factor - society has a duty to the entire community, but the doctor's fiduciary duty has been to the patient in front of him. We've pretty much held that line over the last 20 years despite the push to make us "gatekeepers" and "managers." (read that, "bean counters." However, a doctor can't afford to financially bankrupt himself to devote care to one patient or to provide free or deeply discounted treatment for so many other patients that he can't provide for his family. (and pay his staff, taxes, rent, etc.)

Every day, our ability to offer increasing levels of technology and pharmaceutical interventions that can serve to keep a body alive longer and as more cells and organ systems fail. It was reported this week that new techniques of resuscitation after cardiac arrest that may benefit - and may harm - thousands of patients.

Each new ability to keep patients alive when they would have died "naturally" puts more stress on the medical judgment element. And puts the doctor in the position of increased likelyhood that he will have to determine the benefit to his patient for more and more invasive treatment. A side effect is that some patients and families may demand that he act against his judgment.

Carried to the extreme, the doctor could become the slave of any family - unable to withdraw from the care of a patient for months or years, forced to change IV's and IV settings, to maintain and adjust the ventilator and dialysis settings, or even to maintain the heart-lung assistance device that slows cell death, even after the heart has died.

When so many doctors agree that the demands to use medical technology on a patient is inappropriate, that's not "Futile care theory," no matter how finely some define it. That's the practice of medicine. For the Bishops to back the doctors in the practice of medicine is not "futile care theory," either.

Where are the doctors stepping up to cast doubt on specific decisions and doctors in the cases that have become so celebrated in Texas? We hear rumors, but I don't see action.

Last year, a good man, a skilled and compassionate doctor, ended up treating Andrea Clark's family while doing his best to treat the patient, herself, but his actions were definitely futile, proved to be of no medical benefit. By treating the family's concerns, he enabled them to agree to stop increasing Mrs. Clarke's level of intervention. He showed wisdom in addition to knowledge, skills and judgment. However, my medical skills and judgment wouldn't have allowed me to go so far as to drain the gallbladder as he did.

Religion and zealotry of one sort or another

The National Review has published an editorial by Colleen Carroll Campbell on the resignation of St. Louis' Archbishop Raymond Burke from his position on the board of that city's Children's Hospital foundation. The Archbishop objected to the invitation to the outspoken (and vocal) proponent for abortion and embryonic stem cell research, Cheryl Crow.

Ms. Campbell states the problem well:

Today’s religious leaders increasingly face a double standard when it comes to their public pronouncements: They can say what they want as long as they express politically correct views or stay mum on hot-button social issues. Where secular pundits and celebrities are given free reign to plead their case to the public, religious leaders are derided as theocrats for injecting religiously derived moral principles into political debates. This stifling of religious voices is intended to prevent religious conflicts in the public square. But it also prevents the most fundamental form of deliberation necessary to the functioning of a pluralistic democracy: honest debates about right and wrong, good and evil, truth and falsehood.

However, I would add that the zealotry of some who complain about activism by any and all religious people in any public dispute is near-religious in itself.

A case in point:

The journal, Nature Neuroscience published an unsigned, unattributed essay in the April, 2007 issue, entitled "Shaky arguments against stem cells: Recent attempts to use scientific findings to discredit embryonic stem cell research are distorting the state of the field." (I'm not sure whether this requires registration to view.)

(Amazing, huh, that the editors could afford so much space for their title, but none for their own names?)

The editorial is nothing but a call for all embryonic stem cell research and nothing short of the same, without comment, without restrictions.

In order to illustrate their point, the authors (whoever they are), discuss an essay written to inform the readers of First Things. The authors (whoever they are) state that the content of the article is "correct," but feel it necessary to stress that the journal is a "conservative Roman Catholic magazine" and cite Maureen L. Condic, Ph.D. for "trying to spin science—both its problems and successes—to fit an anti-scientific purpose."

In fact, they seem most offended that Dr. Condic commented at all.

As I wrote the editors, the editorial reflects a deep bias and a "spin" of its own, discrediting their journal and "distorting the state of the field," indeed.

If we knew who these anonymous authors were, perhaps we could ask them why their own position is "right" and the Dr.s' is "wrong." I would also ask them why they insist on bringing religion and politics into the debate, when Dr. Condic so obviously - as they state - avoided both.

End of Life Debate (Emilio, Texas Law)

The debate continues on the end of life decisions and care of the poor child, Emilio Gonzales, at Wesley Smith's blog.

Please take a look at the misunderstandings in the conversation and the fantastic review by "woundedpig," whose comments begin at about the 27th post.

It does appear that the lung collapses were due to atelectasis, rather than pneumothoraces and there were no chest tubes. That doesn't change the facts that no one "refused" Emilio a tracheostomy. It means that he was unstable and not a candidate for the procedure.

There's also links there to the House State Affairs committee hearing of April 25th, if you want to see some of the debate at the Texas Legislature - and some of the people involved. The hearing began in the morning, when Representative Delisi laid out her bill. After a recess for the regular House session, the Committee resumed late that afternoon and ran to 5 AM. I couldn't stay because I had a 6:30 AM meeting in Dallas the next day. But the other testimony is worth some time -- after you read "woundedpig's" comments, though!

Transhumanism Seminar in Second Life

Transumanar, a site devoted to transhumanism, has announced a virtual, online seminar on Transhumanism and Religion in Second Life.

I'm not sure that I'm ready for a Second Life, and I always get bored when I try to come up with an avatar. But, I may have to check this out, if possible. (In my First Life, I'll be at the Texas Medical Association annual meeting the rest of the week.)

Economists Discuss Bioethics (healthcare, neuro-economics)

There's no answers, just more intelligent and informed questions, but here's an interesting discussion on "Money Driven Medicine" at the blog, Marginal Revolution.

One of the blog owners, Tyler Cowen, has a piece in the business section of today's New York Times, "Enter the Neuro-economists: Why do investors do what they do?:

Vaginal approach to gallbladder removal

Or removal of the appendix through the mouth?


I finished my residency training in 1993, and was privileged to witness some of the first "laparoscopic" gallbladder removals on one of my rotations with some private surgeons. After 5 years or so of observing and assisting with the old technique that required a 7 to 10 inch incision at the right upper abdomen and months of recovery, I was used to patients lying very still and needing encouragement to breathe after the surgery. I nearly fell apart myself when, just an hour after we removed her gallbladder, one of my patients sat up in bed. I've never moved faster than I did that time, trying to catch her before she tore her wound or fell out of bed when the pain hit!

My first reaction to this story was one of alarm about possible harm due to trying a new, risky maneuver, just because it's surgically possible.

I wasn't sure how much of my distaste was a woman's reaction to invasion through the vagina. After I read the description of the appendectomy through the mouth, I decided that it's a true caution about the risk of such a route.


The biggest problem with recovery from surgery is the trauma to the tissues surrounding the surgical site, especially the muscles that are cut and sewn.

I finished my residency training in 1993, and was privileged to witness some of the first "laparoscopic" gallbladder removals on one of my rotations with some private surgeons. After 5 years or so of observing and assisting with the old technique that required a 7 to 10 inch incision at the right upper abdomen and months of recovery, I was used to patients lying very still and needing encouragement to breathe after the surgery. I nearly fell apart myself when, just an hour after we removed her gallbladder, one of my patients sat up in bed. I've never moved faster than I did that time, trying to catch her before she tore her wound!

The new technique allowed for us to remove the gallbladder - and later, the appendix (and other stuff) - by making 3 or 4 cuts, all less than an inch and using instruments and a camera that allowed remote or video-guided surgery. Without all that cut skin and all those layers of muscle, patients got better, faster.

It's almost routine to perform hysterectomies through the vagina these days. But let's face it, in this case, everything's right there. The surgeon just has to watch for the blood vessels, the bladder and the rectum, and virtually no muscles have to be cut, at all.

Either of these operations would require muscles and "surface" tissues to be cut, and each require that the surgeons' instruments pass other organs. There's also the problem of making the surgical field sterile and maintaining infection control.

With removal of the gallbladder, there is also the risk to the liver, and especially, the common bile duct from the liver to the intestines. For that matter, an oral approach to the appendix would require reaching past the lungs, the diaphragm, the liver and the intestines, unless the instruments can be passed through the esophagus and stomach. (How would you intubate this patient, protect her lungs, or handle the leaks of acid from the stomach into the abdominal cavity?

The surgeons quoted in the New York Times article are proponents of "no scar" surgery.

I'm a little concerned about the way they "read":

Dr. Bessler said his patient agreed to the procedure (two others had declined) because he told her he thought it would have advantages for her, and she accepted his judgment. She was the first in a study that is to include 100 women who need gallbladder surgery, appendectomies or biopsies taken from inside the abdomen. All the procedures will be done through the vagina.

Dr. Dennis Fowler, another surgeon who participated in the operation, said the team began experimenting on women because “incisions in the vagina have been used for a variety of procedures for decades, and proved safe with no long-term consequences.”
. . .
The operation took about three hours, twice as long as the usual laparoscopic surgery, but it was the team’s first operation on a human, and the time should decrease with practice, Dr. Bessler said. Also because it was the first time, to be on the safe side, the doctors did make three small openings in the abdomen for surgical tools. But their ultimate goal is to perform the operation entirely through the vagina.

Artificial Intelligence vs. believers

The subject of believers and those who actively oppose them is only tangential to this blog. However, anyone exposed to cutting edge technonology, futurism, and, especially, transhumanism and enhancement will eventually run across at least one fundamental atheist.

George Dvorsky, transhumanist and anti-theist, has published his review of a movie called "The Jesus Camp." In fact, he titled the post, "The Jesus Camp and the art of Brainwashing Children."

As interesting as it is that Mr. Dvorsky discusses the mimetic convergence of Islam and Christianity rather than noting the divergence(since both teach that we can trace our history back to Abraham and his God), I was stirred to post from the gallery of the Senate of the Texas Legislature by this remark of one of the visitors to the site:

The best news, however, is that AI, when it is invented, will be immune to religion; I suspect it this will remain true even if the AI is designed by a deeply religious person. (anyone agree/disagree?) And what's the likelihood of a religious person being the maker of the first AI? Are there many christian AI programmers?

And the world didn't end (Supreme Court Partial Birth Ruling)

I'm minding my own business, visiting a few hundred blogs in an effort to complete the database on Bioethics Internet resources for my Bioethics capstone project, and one of the headlines said that the Supreme Court had up held the Federal ban on Partial Birth Abortions.

There was no earthquake, no sonic boom, and I might have slept through the whole thing!

It appears that Justice Kennedy wrote the opinion for the majority.

Watch the National Review "Bench" blog for the analysis. (And FreeRepublic for the people's reaction.)

As I said, the world didn't end, and this ruling evidently specifically did not rule on Roe v. Wade, the legitimacy of the Court's ruling on abortion, or even overturn Carhart, the previous Supreme Court case on partial birth abortion.

Justice Ginsburg, at least, wrote a dissent predicting the end of the world for women.

I expect the conversation to get ugly.

The procedure that intentionally delivers part of a child in the second or third trimester in order to decrease the needed dilation of the mother's cervix by reducing the size of the skull is a particularly barbaric example of abortion. I believe that only the extreme pro-abortion advocates (those who see any restrictions as placing the entire elective abortion "right" at risk) are truly supportive of this procedure.

Those who are so pro-abortion as to see this ban as "the end of the world," shouldn't worry: there will still hysterotomies, saline abortions and multiple ways of killing the child in utero.

(There may be a shortage of fetal tissues for research, however.)

More Complaints About Texas Legislator

A blogger over at the Daily Kos is complaining about the Texas State Affairs meeting on HB 225. The complaint is that people with disabilities had to wait until the early morning to testify.

There's more comments at the South Texas Chisme: Sneaky Republicans ban stem cell research funding" (See the problem with the headline? Nothing has been banned, other than funding for a certain type of stem cell research that carries restrictions from the NIH, as well as being unethical.)

More at "Brains and Eggs," and Texas Freedom Network (self-defined as "A Mainstream Voice to Counter the Religious Right") has an article and a petition.

Perhaps I should tell them some of the realities about testifying in front of the Texas State House Affairs Committee.

1. First, Chairman Swinford believes that everyone should have their say. He never puts time constraints on witnesses, unlike some of the other Chairs, who have lights and buzzers and 3 minute limits. We all mutter, but we're all grateful when it's our turn.

2.The Chairman always lets kids go first. The other bill had children as witnesses, none of us there to testify on HB 225 had brought children.

3. Those early morning meetings are always interrupted by the House meeting and resume when the house adjourns for the day.

4. We should just be thankful that only two bills came before the Committee the other night -- they might all still be there.

"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.

Yellow Brick Award

The Yellow Brick Award will note those in the Biotech and Bioethics research and policy communities who attempt to lead us down a winding, deceptive path, using explosions, smoke and mirrors, pulleys and levers, novel definitions, distraction, projection and destruction. There are usually at least a few wicked witches, projectiles (not necessarily houses), lots of hot air and maybe a few gene-mod flying monkeys and a forest of threatening trees.

When we look behind the curtain, we find that with stem cell research and abortion, we're just like Dorothy and the gang: we already have what we thought we needed. We just didn't know how to use it or notice when we did.

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."

Enough: ultrasounds, abortion, women and blood

While calling us "anti-choice," some "pro-choice" men and women are beginning to look at the true nature of what is being chosen. They're noticing that we who oppose abortion are more likely to accept the woman with an unwanted pregnancy and championing the laws that make adoption and parenting a true choice. They're noticing that we have valid reasons, too.

The Family Research Council blog has a beautiful post quoting the words of one of the many "pro-choice" women that are being convicted about the humanity of the unborn child.

In the May, 2007 Atlantic, Caitlin Flanagan recounts a heart wrenching review of two books, The Choices We Made, and The Girls Who Went Away, of abortion, maternity homes and the girls and women who are and have been impacted by it.

Along the way, she tells us,

But my sympathy for the beliefs of people who oppose abortion is enormous, and it grows almost by the day. An ultrasound image taken surprisingly early in pregnancy can stop me in my tracks. In it is much more than I want to know about the tiny creature whose destruction we have legalized: a beating heart, a human face, functioning kidneys, two waving hands that seem not too far away from being able to grasp and shake a rattle. One of the newest types of prenatal imaging, the three-dimensional sonogram—which is so fully realized that happily pregnant women spend a hundred dollars to have their babies’ first “photograph” taken—is frankly terrifying when examined in the context of the abortion debate. The demands pro-life advocates make of pregnant women are modest: All they want is a little bit of time. All they are asking, in a societal climate in which out-of-wedlock pregnancy is without stigma, is that pregnant women give the tiny bodies growing inside of them a few months, until the little creatures are large enough to be on their way, to loving homes.

These sonogram images lay claim to the most powerful emotion I have ever known: maternal instinct. Mothers are charged with protecting the vulnerable and the weak among us, and most of all, taking care of babies—the tiniest and neediest—first. My very nature as a woman, then, pulls me in two directions.

Abortion hurts us all. As Ms. Flanagan says, abortion has left a trail of blood. It doesn't matter whether the abortion is legal or illegal, the blood flows from the cuts made by the culture that makes so many women throughout history and all around the world believe that they have no choice other than to choose this child or their lives, this child or their future, or (Lord help us) this child or his father.

It's past time to look at abortion and say, "Enough."

Judge rules to restrain hospital on Emilio Gonzales

I'm very glad that the judge in Austin has ruled that Children's Hospital can't remove him at this time from the ventilator and that he has named a guardian ad litum, to look at the evidence from the baby's best interests.

The Austin News 8 TV news also tells us that Emilio's mother and her lawyers have another doctor who will step in to evaluate his condition and whether he is a candidate for a tracheotomy.

Hopefully, some new voices will bring the two sides together for Emilio. I'm convinced that the doctors and nurses caring for Emilio have been doing their best, saving Emilio's life daily. And I'm sure that his mother is getting through the whole ordeal the best way she knows how.

For more information, you can read the Ethics Committee Report at the North Country Gazette, published in a same March 18th post by June Maxam.

Juvenile Diabetes Adult Stem Cell Cure?

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

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

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

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

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

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

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

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

Embryos and cloning on Senate agenda this week

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

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

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

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

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

Washington Post April 8, 2004

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

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

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


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

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

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

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

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



Call your Senators every day this week!

How not to question research

What bothers me most about this controversy is that the whole thing began when the authors announced that they were about to release their raw data. Where is the discussion about the evidence in question, rather than historical questions without the numbers.

(I'll admit that the numbers boggle me - I'm not sure how one source could differ from one another by one third to one million deaths, without other groups noticing.

However, I can't help wonder how even 5 teams could interview 38 families during the violence that those teams were reporting.)


Last October, the journal Lancet published a report (available by subscription only and I don't have access) by Les Roberts and Gilbert Burnham claiming that Iraqi citizens suffered hundreds of thousands of "excess" deaths due to the war. Last month (Feb 28th online and in the March 1 issue), Nature published a news article (available by subscription only, excerpts below) critiquing the study:

On paper, the study seems simple enough. Eight interviewers questioned more than 1,800 households throughout Iraq. After comparing the mortality rate before and after the invasion, and extrapolating to the total population, they concluded that the conflict had caused 390,000–940,000 excess deaths (G. Burnham, R. Lafta, S. Doocy and L. Roberts Lancet 368, 1421–1428; 2006). This estimate was much higher than those based on media reports or Iraqi government data, which put the death toll at tens of thousands, and the authors, based at Johns Hopkins University in Baltimore, Maryland, and Al Mustansiriya University in Baghdad, have found their methods under intense scrutiny.

Much of the debate has centred on exactly how the survey was run, and finding out exactly what happened in Iraq has not been straightforward. The Johns Hopkins team, which dealt with enquiries from other scientists and the media, was not able to go to the country to supervise the interviews. And accounts of the method given by the US researchers and the Iraqi team do not always match up.

The authors of the original study have answered and Nature has published it:

In our opinion, your News story about our Lancet paper "Death toll in Iraq: survey team takes on new critics" (Nature 446, 6–7; 2007) has confused the matter rather than clarified it. You outline three criticisms of our work: that there was not enough time to have conducted the survey; that the sampling method suffered from a 'main-street bias'; and that the study team fabricated the data (the last being attributed to anonymous "researchers"). These criticisms have been previously addressed, and have little merit.

On the first point, the 1,849 interviews in 49 days described in our study suggest that 38 interviews had to be conducted each day by our eight interviewers. Although introducing themselves and explaining the confidentiality agreement might have taken interviewers several minutes, the five-question interview would take only a couple of minutes for most households that reported no deaths. The idea that eight interviewers could not conduct a total of 38 interviews in a day is not credible.

Second, we dismiss the suggestion that our sampling over-represented main streets, where car bombs are more likely. As stated in our paper (G. Burnham, R. Lafta, S. Doocy and L. Roberts Lancet 368, 1421–1428; 2006), when excluding the statistically outlying cluster of Falluja from the first report, we estimated 98,000 (95% c.i.: 8,000–194,000) excess deaths versus 112,000 (95% c.i.: 69,000–155,000) over the same period with the second survey. The first survey was done selecting random starting points with a Global Positioning System unit. The second used the random street-selection process, which is being criticized as biased. It rarely occurs in the field that two sampling methods are used allowing for comparison, and here the results are nearly identical. Moreover, there is no plausible mechanism for a significant main-street bias to operate, because only 15% of all deaths are from car bombs and other ordnance, and because most violent deaths are believed to occur away from the home.

Third, as for the accusation that researchers fabricated the data, we are ready, willing and eager to have an established international authority take a sample of the cluster forms and go to the field with our interviewers to verify the findings. Until that time, the Coalition and Iraqi governments' statements that during the first three years of occupation, Iraq's violent-death rate was lower than those of Russia, Estonia, Latvia, South Africa and Kazakhstan remain an implausible contrast with our findings.

When Nature called one of our study members in Iraq and asked if local officials joined them during the survey, that individual later clarified to Nature by e-mail that 'local officials' did not mean local clinicians and colleagues. This was inaccurately reported in the Nature summary along with a statement by our co-author that interviewers often worked alone. These points were wrongly cited as contradictions between the study team members in your News story.

All reports will eventually have "criticisms that dogged the study", if previously addressed criticisms with so little merit are given a voice in the press.

Mama's last lesson

Easter Sunday, April 8, 2007 would have been my mother’s 70th birthday. Helen Margaret Jernigan Burnett, “Mama,” died from complications of thymic carcinoma last August.

Mama is probably the source of my addiction to arguing and politics. Some people might think it comes from being the oldest daughter of a Baptist preacher, but I believe it comes from being the daughter of a certain Baptist preacher's wife.

Mama was a teetotaler, prolife, conservative who believed in equal opportunity for anyone who would do the work, but also worked to help others. She and Daddy stopped to “early vote” on the way to see the chest surgeon – just in case her surgery was scheduled before the election a few weeks away. She was semi-famous in her hometown as the food demonstration lady at the local Wal-Mart, the one who handed out samples and root beer floats. She won awards at work for leading fund raising and selling at the store, and ran the early morning Senior Citizens Bingo. Most of all, she was the best “Grandmama” in the world.

As Daddy pushed her wheelchair into the hospital for what turned out to be her last admission, she suddenly looked up at the people around her and said, “I have the best insurance in the world: Jesus Christ!”

It turned out that she was suffering a series of strokes that would steal her ability to do even basic self-care and make her delirious most of the time. Daddy, my sister or I took turns to be with her most of the time; feeding her, helping with her baths and trying to help her control her pain. I wasn’t always patient and I’m afraid that I preached a few of the lessons I learned from her, back at her. But I was better at doing what I could for her than I would have ever thought.

In spite of what I knew of her condition and prognosis, Mama’s death was totally unexpected. Evidently, she had her final stroke while in the MRI, as I sat at the head of the machine, singing to her and trying to keep her (both of us) calm.

I’ve often heard people say that they wouldn’t want to be a burden to their children. Needing someone else to feed us and wipe our chin when we can’t hold the spoon, much less assist us in performing much more intimate acts of hygiene, seems to be the worst thing we can imagine.

I’ve never had a good answer for patients or family members when they express this fear to me. Now, I know that the worst thing that I can imagine is living the rest of my life without having fed Mama, washed her, and rubbed her back on that last day.

The faith that she and Daddy surrounded me with as a child makes me sure that Mama is in heaven. But it’s the memories of caring for her those last few days that let me live here on earth knowing that I loved her as best I could when I could. Mama's last lesson was that we owe it to our loved ones to allow them to care for us, for their sakes.

End of life on the internet

LifeNews and Channel 8 TV in Austin, as well as several bloggers are reporting on the denial of the temporary restraining order for Emilio Gonzales in Austin, Texas.

Unfortunately, there are quite a few errors in the story.

I'm disturbed that the false information is spread and that there seems to be no problem in accusing the doctors of wanting to cause Emilio to die. In fact, the disease is causing Emilio to die, and his mother has said as much. The nurses and doctors have fought to prevent Emilio from having a "natural" death.

The doctors have worked with Emilio's mother, and have kept him alive in spite of repeat episodes where the baby's lungs developed a leak - or a "pneumothorax" - caused by the very high ventilator pressures required to keep Emilio's oxygen levels up.

Somehow, the North Country Gazette obtained the Ethics Committee Report and they have posted it on the Internet. I have copied part of the report at this post.

A pneumothorax allows air to escape into the chest around the lung, the pressure outside the lung grows each time the ventilator pushes air into the lungs. The lungs will collapse unless a chest tube is placed, the air is sucked out of the chest, and the lung reinflates. The ventilator pressures, high concentrations of oxygen and the collapsing of the lungs each cause further damage to the lungs.

The same high pressures explain why the doctors did not put in a tracheotomy earlier. The "trach" would have leaked if placed while the lungs needed such a high pressure.

There's no question of the diagnosis and the vitamin IV was not one of the "life sustaining treatments" and probably was not needed at all.

There's no doubt that the child has Leigh's syndrome. The syndrome is diagnosed by a group of symptoms, findings on the exam and sometimes by labs. In Emilio's case, there are also MRI's that show areas of the brain are dead and there are EEG's that show he has seizures one third to one half of the time. There are some tests for finding whether and how many or how severely the cells are affected with a genetic defect that makes the mitochondria - the energy factories of the cells - damaged. In the worst form, the type that causes "necrosis," or cell death, of the brain cells, children die very early. An alternate name is "necrotizing encephalomyopathy," meaning that the nerve and muscle cells are affected.

What is not known is the exact nature of the genetic defect that is causing the child's cells to die. There are at least several dozen and from my reading, I'll bet there are a hundred or so genetic defects that can be inherited or may be a new mutation. Some are "X-linked," meaning they are passed through the mother. Some - especially the X-linked forms - disturb the metabolism of the pyruvate dehydrogenase enzyme within the mitochondria.

In the past, some children with the form of the syndrome that changed the metabolism of pyruvate dehydrogenase got better after given high doses of IV thiamine. Now we know that that only works for certain types of defects that cause the syndrome. Other people get better with Co-Q 10 or some other diet change. (The article that the lawyers used to "prove" that the doctors were denying needed therapy was from 1974. There is much more known about the Sydrome than was known then - for one thing, more is known about DNA and certain mutations. However, these types are usually much more slow in developing and it's much more likely that the docs have been able to order tests for this specific defect - the DNA is evaluated.

While the hospital ethics committee did vote behind closed doors, they heard the testimony of in a hearing that included the lawyers, Emilio's mother and at least one employee of Texas Right to Life. No one is disputing the facts of the report.

Doctors understandably can debate and discuss medicine in a closed conversation, without lawyers and non-medical family members present. How else could they freely discuss the case, without fear of more lawsuits and/or while using the exact medical terminology that doesn't always mean the same thing to lay people that it does to doctors?

The difference is between those who want to keep Emilio alive no matter what pain he is caused by his treatments, no matter how many times his body must be invaded by tubes and needles while his brain tissue - and probably his muscles and intestinal lining as well - dies as the ventilator forces air into his stiffened lungs.

How many needles will Emilio have before his mother changes her mind and lets him go in peace? How many times will he be snatched back from the edge of death by the doctors before he is allowed to live - even a short time - without the pain and irritation of chest tubes, ventilators that push air into him, etc.?

There's no mention of removing the food and water because Emilio's brain does not cause him to breathe without the ventilator. If the ventilator is removed before the damaged areas of the brain heal -- a very unlikely scenario in children without Leigh's disease -- Emilio will die within minutes. The disease will kill him, not the doctors. Removing the ventilator will allow - not cause - him to die.

One of the lawyers has been posting about Emilio at Wesley Smith's blog since mid February.

And yet, neither of the lawyers mind saying things like,

People who could profit from an innocent person’s death should not get to decide when it occurs. Whatever the hospital’s motives are for pushing to end Emilio’s treatment, a child's life outweighs all other concerns--whether it’s to cut costs, or for convenience, or something else,” said Carden. “And furthermore, the twisted state law that allows hospitals to exterminate disabled children over their parents’ wishes needs to be changed.”

There is no profit for the doctors - the child has Medicaid and Medicare, according to what the lawyers and Texas Right to Life staffers have told me.

It is wrong to falsely accuse. It will not help Emilio. I sincerely doubt that it will help Emilio's mother get ready to let him go. And many people are being made angry and sad about the doctor's, hospital employees, nurses and even the Bishop of the Diocese of Austin's "murder" of Emilio. (The post at ProLife Blogs that had that last has been "snipped" to remove it, but the note of protest about accusing the bishop is still there. The quotes from Melanie Childers are still online at the North Country Gazette.)

About those ultrasounds before abortion

Over the last few days, Kelly at Blog.Bioethics.net has been blogging about House Bill 3355, passed in the South Carolina, which will require the abortion doctor to review the ultrasound with the woman or girl at least one hour before the abortion. The woman has to sign a statement that she's received the informed consent and a review of the US.

Kelly and several of the other visitors at the site are concerned that the woman who has made the choice to have an abortion is being unduly influenced, browbeaten and/or the target of images capable of emotional blackmail. (Words from the bloggers are in italics.)

Oh, and "a guy can go around and have sex until the cows come home,he's never going to have to deal with the emotional decisions attached to an unwanted pregnancy."

But, somehow, it's no big deal, anyway.

The conversation is the same one we've been having for 30 plus years, but you might want to take a look.