Type I diabetes and cord blood

Researchers at the University of Florida have treated children, aged 2 to 7, with infusions of their own stored cord blood, with some improvement in insulin production and control of blood sugar.

No one knows the exact mechanism that causes the disease we know as Juvenile or Type I Diabetes Melitus (DMI), but it is thought to be due to some combination of auto-immune disease (when the body's immune system causes damage to its own tissues) and possibly an infection, along with an unknown genetic susceptibility. Not only do the patients make antibodies against their own insulin-producing cells, they also make antibodies against their own insulin. It appears that the cord blood contains regulatory T cells which reverse some of the effects of the DMI on the pancreas.

From the University of Florida press release:

UF researchers identified children recently diagnosed with type 1 diabetes whose families banked their
umbilical cord blood at birth. Most were still producing a small amount of insulin. The researchers then gave seven patients ages 2 to 7 intravenous infusions of stem cells isolated from their own cord blood. (They have since treated an additional four children.) The patients were evaluated for the next two years to measure how much insulin they were making on their own and to assess blood sugar levels and the function of key immune system cells.

In the first six months, they required significantly less insulin — on average 0.45 versus 0.69 units of insulin per kilogram per day — and maintained better control of blood sugar levels than children of comparable age with type 1 diabetes who were randomly selected from the clinic population. The researchers also noted that the children who received cord blood infusions had higher levels of regulatory immune cells in their blood six months after the infusion, on average 9 percent of the total cell volume compared with 7.21 percent at the time of infusion.

“This isn’t a cure-all. We think that giving these cells is essentially providing some immunotherapy and downregulating the autoimmunity these patients have,” Haller said. “Realistically, we hope to protect what’s left of their insulin-production for an extended period of time. We think the immune regulation hypothesis is more likely than the hypothesis that stem cells are forming insulin producing cells on their own.”

The idea would be to intervene and repair any early damage during the “honeymoon period” many patients enjoy — the first several months after diagnosis during which insulin needs are minimal, he added.

The results are consistent with what we already know about Type I diabetes (DMI) and the stem cells that some receive from their mothers before or at birth. The men and women who were found to have functional stem cells from their mothers did not have complete remission of their DMI, either.

"The tie goes to the speaker, not the censor"

Whether you see today's ruling as "weakening" or "slapping," or "trimming"

the McCain/Feingold campaign laws, you've got to appreciate the simplicity of this statement by Chief Justice Roberts:

"Discussion of issues cannot be suppressed simply because the issues may also be pertinent in an election," Chief Justice John Roberts wrote for the majority. "Where the First Amendment is implicated, the tie goes to the speaker, not the censor."

Who would have thought? Free speech in elections!!!

More equal or less?

A self-defined troll, Siricou Raven, asks,

Merely being human genetically isn't enough - so what do humans have that makes them protected over all other species? And when do they aquire whatever this is?

SR, I don't have to weigh, measure and evaluate - you do. You are the one asserting that "being human genetically isn't enough."

Why isn't being human enough?

The problem is more that you find it necessary to justify killing some humans and so you are the one looking for that something that makes some humans less "protected over other species." A more precise way to phrase your premise would be,

"[W]hat do humans have that makes them protected" - from other humans - "over other species," -- while still protecting yourself?

I, on the other hand, follow long-standing philosophic tradition that all humans have the right not to be killed, and the slightly less common tradition that every member of our species is human-enough to be protected from deliberate killing and enslavement. (As I say, "We're the only species having this conversation.")

I believe that anyone can come to the same conclusion - with a little study of biology, logic, history, and even some imagination.

The biology is self-evident. Follow the embryology, anatomy and physiology. The one-celled embryo is the same entity as the rational adult. Our repetitive discussions about "why" and "when" are simply more proof of the continuity, rather than any discrete discontinuities.

It goes against logic to proclaim that "Some of us are more equal than others."

And it requires a lot of energy to defend your philosophy. Energy used up in defining, renaming, listing characteristics and measurements. Then, you need convoluted laws, an army or police force trained to discriminate and protect the "special" people.

If you want to skip logic and efficiency, study the subject of human rights from a historical perspective: Historically, the more inclusive a society, the more freedom for all. Societies that discriminate spend too much energy protecting the special people and their "right" to kill and enslave others.

Even the societies with historical caste systems, where the discrimination is internalized all along the spectrum of human-ness, exposure to ideas about human rights - or the birth of a William Wilberforce, Susan B. Anthony, Ghandi or Martin Luther King, Jr. - weakens former "protections" for the privileged. Society changes. (Far too often, after a period of violence between the "more equal" and "less equal." The dispute about the humanity of embryos created in the lab won't follow this pattern.)

Failing logic, efficiency or the effort to study history and sociology, try imagination.

In the West, children who could have been legally aborted are questioning the assumptions of their mothers' generation about "personhood." They can imagine that they were at risk - they empathize with their missing siblings.

It's hard for me to avoid imagining the outcome of experimentation on the embryo. I've got the examples of how humans have exploited humans in the past. (Last night, I was reading about the Nuremberg trials.) For the imagination-deprived, try reading William Saletan's confused discussion about "Making Manimals," the current experimentation on human genetic material.

Or, you could read some of the wealth of Science Fiction speculation on the results of created-less-than-humans. Recently, there's "Never Let Me Go." For other speculative fiction on the use of human offspring by their creators, read Lois McMaster Bujold (Free Falling, or the Miles stories), or David Webber. One of my favorites is Nancy Kress' Beggars in Spain (a good review, here).

(wow - don't get lost following Nicholas Whyte's links - but do peek at this post, with a link to a page with a link to a 1927 "home movie" of a meeting between Madame Curie, Bohr, Eistein, and the gang.)

Christian Docs' Ethics on The Moral Worth of Human Life

Yesterday, at the annual meeting of the House of Representatives of the Christian Medical and Dental Association, three statements on ethics were approved. I don't have all of the text or the final versions of any of them at this time and will report on them in more detail later, but I would like to brag on the our Ethics Commission and the work of the House. (I'm the Chair of the Family Medicine Section.) Watch for more here and - hopefully - in the Press. I'll post links as soon as they're published on line.

The Chair, Dr. Robert Scheidt also gave one of the workshops on Conscience issues, which I'll discuss after I get home. At the meeting, he introduced statements on "Abuse of Human Life," "Human Stem Cell Research and Use" and "Human Life: Its Moral Worth."

These are statements from an unabashedly Christian world view - with strong logic and historic background. And some of the most elegant language on "person," the image of God, and the moral worth of human life. Here's a bit of the wording - draft version:

Every being of human origin is a person. A person is not a Homo sapiens with the superadded quality of "personhood." Some, however would attempt to withhold moral worth from human beings unless they "qualify" as persons. The status of "personhood" cannot be conferred by society.

The beginning and continuity of the moral worth of human life are concurrent with human life itself. Human worth begins with the one-cell human embryo and lasts lifelong. A living human being is an integrated organism with the genetic endowment of the species Homo sapiens. . . . Thus a human being, despite the expression of different and more mature secondary characteristics, has genetic and ontological identity and continuity throughout all stages of development from formation of the human being until death.

There is beautiful language on the image of God, the sacred nature of human life, and the love of God. I will post these more fully as soon as I get home. Now, I have to go catch a 7 AM plane.

Pay for embryo destruction added to Senate Bill

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

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

From the Houston Chronicle:

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

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

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

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

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

The Veto vs. the Big Picture

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

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

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

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

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

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

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

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

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

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

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

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

Animal Farm: Trojan Pigs and Devolution of Standards

Correction, here: Another blogger The same poster that found it necessary to rant that Fox and CBS wouldn't advertise condoms on the Bioethics.net Blog also posted on the Women's Bioethics Blog. Blog.bioethics.net has been "down" since I posted yesterday - Coincidence? (Update June 21 - they still haven't posted my post.)

There's a link to the commercial, which I have to admit, has some humor to it.

So many puns, so little time.

Trojan could have appropriately used horses, but chose pigs to represent men. Perhaps -if I can use Alexandra's word - it's due to the devolution that produced the same low standards that makes them think a men's room condom dispenser could change a woman's mind about having sex with a pig. Yeah, when "pigs fly."

Alexandra comments on the hypocrisy of TV networks that would deny anyone "sexual pleasure with a condom."

Come on! As the commercial shows, the vending machine is in the bathroom at the club. With product placement like that (for the condoms as well as the men and women) what difference is a commercial going to make to the rate of "unintended teen pregnancy"?

I know, I know. There's actual bioethics news out there. Wesley Smith has posted on ACT's claim to have finally done the experiment they said they did, before. There's Ian Wilmut's plea for human-animal hybrids, not to mention his being named "feature editor" for the new website, "Nature Reports Stem Cells." And there's even "Skinny Water."

Can't resist ending with a line from one of my favorite pigs: "That's all folks!"

Who needs these ads?

Blog.bioethics.net, the blog of the "American" Journal of Bioethics editors and pseudoeditors, are protesting the fact that some TV networks won't sell advertising time to a condom manufacturer. As I commented on their site, the ed's and pseudo-eds have forgotten that most Americans don't live on a college campus. ((Where one in four the residents contract Sexually Transmitted Diseases each year and where nearly that many - one in five - girls are sexually assaulted during their stay.)

How many of us have had to explain "Gentleman's Club" billboards to a 4 year old? How about finding ourselves needing to teach our 7 or 8 year old who just saw a commercial what a condom is?

Since we're talking "should:" I'd go so far as to say that most people believe that sex is properly private and that children shouldn't be exposed to sexual behavior of adults around them.

There, I've said it.

I guess parents could turn condom and K-Y jelly commercials into a sort of lesson that kids used to get on the farm when they saw sex between animals at a young age. Of course, those kids were exposed to birth and death in the home and in the barnyard, as well as watching their own food be killed and dismembered, too.

And, since I'm saying things that need to be said: (in my opinion) the constant public (in media such as TV and the Internet) the "selling" of sex of all kinds at at all hours of the day and night has resulted in an unintended social experiment.

That experiment has failed: the age of first sex has declined, and the variety and incidence of STD's has increased, even in those who report that they use condoms - and far too many don't, and don't believe that they're at risk. I don't believe it's healthy, physically or mentally.

Racism, politics, and really big numbers

Last week's announcement that three different labs have managed to not only reproduce work showing that certain genes are responsible for embryonic-stem-cell-ness, but actually managed to turn adult cells into embryonic-like stem cells has been widely reported and comment upon.

Times Magazine displays blatant racism and not a little naivete in their report, "Japan gets ahead of the curve":

But it was March 2006, just months after the South Korean stem-cell scientist Hwang Woo Suk—who had become an international sensation after claiming to have cloned a human embryo, a first—had been exposed as a fraud. As another Asian stem-cell scientist announcing a surprise advance, Yamanaka knew his peers would put him under the microscope. (emphasis mine)

Yep, all them furinner's look alike to us.

Actually, the Times reporter mentioned the most important factor in any increased scrutiny and pressure from Yamanaka's peers: ". . . because Yamanaka did not use human embryos, his technique offered researchers everywhere a way to sidestep the ethical controversies that have dogged the field since its birth."

We've been treated to examples of politics in science each time non-destructive stem cells news breaks out. I reported on the comments at the American Society of Bioethics and Humanities meeting last October. David Stevens, MD, CEO of the Christian Medical and Dental Association describes the scenario:

. . . proponents rushed to the microphone to do damage control and claiming we must continue embryonic stem cell research since we can't predict which technique will provide cures. With 1,200 clinical studies underway using adult stem cells and none using embryonic ones as well as these two breakthrough studies in the last year, it is becoming a pretty sure thing on simple pragmatic grounds where we should be putting our tax money. It is like predicting whether the San Antonio Spurs are going to beat your local Saturday afternoon pick up basketball team.

The emperor has no clothes but continues to ride smiling through the public. Sooner or later the people notice."

(Go, Spurs, Go! Yeaaay Champs! Sorry, couldn't resist.)

We've read that the results we keep seeing from adult stem cells are simply a matter of the numbers - more US tax dollars are spent on adult stem cell research than on embryonic stem cell research, and embryonic stem cell research is much newer than adult. But let's look at the facts: Yamanaka did his work in Japan, and Nature is published in the United Kingdom. Nope, no influence from US tax payer funding or the lack there of. Perhaps it's just that non-destructive stem cell research actually produces reliable, frequent results?

But maybe, just maybe, if we get out our tin hats and/or risk assuming a duty to die, we might contemplate there's Something Else going on. A UK conspiracy? Or is Someone higher up messing with the United States Congress?

Dr. Stevens:

Ironically, the day this bill passed last fall, the news announced the breakthrough study that showed that amniotic stem cells could become endoderm, ectoderm and mesoderm. They have all the benefits of embryonic stem cells but none of the risks. They don't turn into cancers, they are readily available, genetically stable and easier to control. This year, the ground breaking study on dedifferentiating mouse skin cells into embryonic stem cells hit the front pages and TV screens the same day as the House vote and stole its thunder. Though this technique has a number of hurdles to cross before being applicable in humans, I'm beginning to wonder if God has a great sense of humor!

(Go, God, Go! Had to do it.)

And Dr. Stevens is not the only one to notice that there are just too many coincidences, what Yogi Berra called, "Deja vu, all over again."

A very funny Washington Post Op-Ed by Rick Weiss, entitled "Darn cells, Dividing Yet Again!" could be used to discuss humans' need to attribute natural phenomena with supernatural explanations with these guys, over at The Edge. Or at least a cosmic conspiracy.

Go read the whole thing, but here's a bit:

Is there a plot afoot?

Lots of lobbyists, members of Congress and even a few scientists are starting to think so.

"It is ironic that every time we vote on this legislation, all of a sudden there is a major scientific discovery that basically says, 'You don't have to do stem cell research,' " Democratic Caucus Chairman Rahm Emanuel (Ill.) sputtered on the House floor on Thursday. "I find it very interesting that every time we bring this bill up there is a new scientific breakthrough," echoed Rep. Diana DeGette (D-Colo.), lead sponsor of the embryo access bill. Her emphasis on the word "interesting" clearly implies something more than mere interest.

"Convenient timing for those who oppose embryonic stem cell research, isn't it?" added University of Pennsylvania bioethicist Arthur Caplan in an online column. (The bill passed easily, but not with a margin large enough to override Bush's promised veto.)

Even some scientists, those exemplars of rationality, couldn't help but wonder if somebody, somewhere, was -- if not out to get them -- at least taking some pleasure in irritating them.

"I don't think this is the most sensitive timing for Nature to release these papers," said Harvard stem cell scientist Kevin Eggan, the lead author of one of the articles that appeared in the London-based journal on Thursday.

Twice in six months. What are the odds?

"Duty to Die" (A Bioethics "Target" if there ever was one)

If the person has lost her moral agency/personhood as I argue, then the person who deserved reward is no longer present to receive it. It is the new moral entity, having done nothing, that receives the reward for what someone else did.

Seriously! "Someone else?"


Yesterday, I discussed the first of two "Target Articles" in this month's American Journal of Bioethics. The second Target Article, "A Kantian Moral Duty for the Soon-to-be Demented to Commit Suicide" by Dennis R. Cooley,Ph.D, seems a good demonstration of what happens when elitist minds forgo ethical boundaries in order to provoke discussion.

Cooley bases his essay on the discussion by Kant of personhood, moral agents, and a duty to one's life and self as an end in itself:

Kantian arguments for morally obligatory suicide are
extremely rare. Many believe that Kant thought suicide
was absolutely prohibited conduct, mostly on the grounds
that no agent could consistently will the generalized form
of any suicide maxim based on self-love as a law of nature.
Therefore, according to this interpretation, Kant would
never require someone to kill herself for any reason. However,
there is a plausible interpretation of Kant’s views
that states, under certain conditions, not only is the person
permitted to kill herself; she is required to do so
as a duty to herself qua moral agent. In situations in
which the agent cannot keep both her physical and moral
lives, killing her body preserves her moral life and dignity
as a person. I will first develop the Kantian suicide
duty to the self and then focus on why it pertains to
dementia patients before they lose their moral status as
persons.
...the example most closely related to dementia patients’
loss of moral agency is that of a man bitten by a rabid dog.
As in the case of the patients, the ill man is not responsible
for becoming ill. However, even though he is innocent
of any wrongdoing related to the illness, Kant states that
the man has a duty to take “his life lest he harm others as
well in his madness” (Kant 1797 [1996], 178). There are only
two choices—each of which is bad—open to the rabid individual:
suicide and madness/loss of personhood. For the
latter, the agent not only loses his humanity by becoming
the physical equivalent of a rabid dog, he poses a threat to
others, which in turn could cause them to lose their humanity
if they are also infected. Suicide, on the other hand, is a
duty he has to himself as a being with human dignity. Although
it is likely to cause harm to others due to the loss of
the individual, if performed with the right mental states and
reasons, the taking of his physical life preserves his moral
agency. He chooses to remain a person, instead of allowing
himself to be degraded by having a moral status lower than
that of a rabid dog.

The good news is that all of the Open Peer Comments object (with one, Ackerman, calling Cooley "elitist"), and it appears that Cooley, himself, believes that he only wrote the essay to provoke discussion. In his "Reply" to the Peer Comments, Cooley (who teaches philosophy and ethics at the North Dakota State University) explains his purpose behind writing the essay, as well as implying that he doesn't accept Kant's assertions:

I knew when writing “A Kantian Moral Duty for the Soon to Be Demented to Commit Suicide” that it would cause a great deal of consternation too (sic) many. First, my interpretation of Kant was heavily influenced by Korsgaard’s double-level theory so well explicated in her “The Right to Lie: Kant on Dealing with Evil (1998).” Second, and most importantly, any challenge to central beliefs on morality, especially when it involves vulnerable populations, always will have this effect. However, I take Mill seriously when he states that:

the only way in which a human being can make some approach to knowing the whole of a subject, is by hearing what can be said about it by persons of every variety of opinion, and studying all modes in which it can be looked at by every character of mind (Mill [1972], 88).

The goal is to understand what others think and argue, and then incorporate the useful parts into a fuller understanding of death duties.

......The position I consider only applies to people when they have dementia causing disease and their full self-hood with its inherent duties to themselves. The need now is to discuss the issue until some practical solutions that respects all those affected are found.

Actually, no, Dr. Cooley, we have no such need.

Trust me: I'll act against my conscience

The title throws you for a loop, doesn't it?

Trust me to do what? Follow the law, when I can violate my own conscience? Practice ethical medicine when I promise not to have any personal convictions to guide me? What are laws and ethics to a person who has no conscience?

This month's American Journal of Bioethics - unfortunately available only by subscription - is devoted to exploring the conscientious objection of pharmacists (and by extension, doctors and nurses, and everyone of us) who refuse to dispense emergency contraception (EC).

I do not believe that there is any evidence that the progesterone-only EC, Plan B, has abortifacient post-fertilization effects. In other words, I believe that anyone who objects to Plan B on the grounds that it causes the loss of a human life is mistaken.

However, I don't believe that they should be forced to perform acts that go against their consciences or subjected to a special conscientious objector review board, as advocated by all but one of the "open peer commentary" on the "Target Article" by Robert F. Card, (Abstract here), "Conscientious Objection and Emergency Contraception."

Card obviously has a bias against those of us who believe that human life begins at fertilization and that all humans have the right not to be killed. Nevertheless, as one commenter, Farr Curlin, MD, notes (It's worth reading all this, trust me):

Card (2007) does not merely claim that practitioners are obligated to provide EC; he argues that they are obligated to do so even if they have a conscientious objection. This last clause may seem harmless on the surface, but a closer look reveals that it effectively saws off the limb on which the first clause and all medical ethics sit. To begin, what is a conscientious objection, but an individual’s judgment that it would be unethical for him or her to act in a certain way? A genuine conscientious objection, even if misinformed, is an expression of a commitment to acting morally, and although religious persons are somewhat more likely to report conscientious objections (Curlin et al. 2007), judgments of conscience need not be informed by explicitly religious ideas. Moreover, all ethical arguments are appeals to conscience. As such, acting conscientiously is the most fundamental of all moral obligations.

....


Indeed, the very act of presenting evidence and making arguments presumes that the one to whom those arguments are directed, whether practitioner or juror, is committed to acting according to their best judgment after taking all relevant considerations into account. It would be useless for an attorney to make arguments to jurors if those jurors were not committed to deciding a verdict based on their best judgment of the guilt or innocence of the defendant. Likewise, it is useless for Card or anyone else to make ethical arguments if practitioners are not committed to practicing according to their best judgment of what is in fact ethical. A commitment to acting conscientiously is as fundamental to the moral life as a commitment to judging impartially is to the work of a
juror.

Corrigendum - or "Correction in Print"

I've learned two new words in the last two days: eponymous ("self-named" or named after the thing itself) and "corrigendum" (a correction of an error found after printing, which is corrected with a separate printed page.) I just had to use the latter in my title.


The journal Nature has retracted (sorry, subscription only) a single figure from a 2002 report (free abstract, here) on the successful identification and culture of multipotent adult stem cells, from the lab of Catherine Verfaillie, Ph.D., formerly of the University of Michigan. Besides witnessing an example of scientific integrity on the part of Nature and the authors, we may also be witness to a demonstration of integrity and ethics within the scientific community.

It's important to note that the actual data and the conclusions of the report are no longer in question, if they ever were. The problem was with this single picture, depicting the results of flow cytometry of the cells identified as multipotent adult progenitor cells (MAPCs). The existence and significance of the MAPCs is not in question. The description of the methods and results of the original team has been blamed for the difficulty of reproducing the experiment.

The Scientist reports that Irving Weissman, Ph.D, formerly skeptical of the conclusion that the adult cells were indeed multipotent, has since worked with and published another report on the MPACs with Dr. Verfaillie's team and now supports her conclusion, at least tentatively:

Irving Weissman, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine in California, co-authored a 2007 study with Verfaillie, and said he believes Verfaillie is innocent of any foul play. Verfaillie "has a long record of solid, reproducible work. I can't conceive that, if there is a systematic error, she participated in it," he said.

"Nevertheless at the very least, the markers associated with the cells [in the Nature study] can't be taken as gospel," Weissman continued. In the case of Verfaillie's MAPCs, he said, "it is conceivable that [Verfaillie] found a way of tissue culture isolation of pluripotent cells that was difficult to reproduce."

There must be room in everything we do for correction of mistakes. We are once again reminded that science is the process of discovering what can be discovered and reproduced in different labs, at different times, using the same methods.

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!