Why most Published Research Findings Are False

Chasing links today, I somehow stumbled upon found this very interesting title:
John Ioannidis, “Why Most Published Research Findings Are False,” PLoS Medicine, vol. 2 (2005), pp. 696-701.

Brush up on your statistics and ability to evaluate scientific literature (and those that report on the same).

Prolonged culture of embryos, stem cells and more Free Stuff

This week's (June 27) Nature.com "Advance Online Publication" contains two "Letters" describing the production of embryonic stem cells from "epiblast" cells, one in mice and rats, one focusing on mice.

Full content is restricted to subscription-only, but you can listen to a discussion about the studies on the free podcast from Nature, here, and the first paragraph of each is available for free, here and here. I believe you can also download the pdf of the Supplementary material for the articles here and here. You can find old podcasts and the English transcripts of previous podcasts, here.

One point that I find interesting is the statement on the Podcast that "what we thought were mouse eS Cells (embryonic stem cells), probably weren't." The second is that, beyond the obvious concerns about increased interest in growing human embryos to a later stage, this research was carried out in human embryos before moving on to mice and rats. From the first reference:

We initially determined that prolonged culture of human ES cells in chemically defined medium (CDM) containing activin A and FGF2 (CDM/AF) maintained their fundamental characteristics (See Supplementary Data). We then tested similar conditions for derivation of pluripotent cells from pre- and post-implantation rodent embryos.

The good news is that the scientists are convinced that these "EpiSC's" - or Epiblast stem cells - will be useful as models for the study of embryonic development and substitute for the human embryonic stem cells, without the limits on US Federal funding. (I'm always fascinated by the interest that British publications have in our US funding schemes and politics.)

If I'm correct in interpreting the importance of this information, scientists should find it easier to do experiments that they've been wanting to do by using rodent embryonic stem cells, now that they know how to find the actual cells, themselves. We will also hear more advocacy for the "culture" of human embryos longer than the previous 3 to 5 days, in order to harvest truly pluripotent eSC's, from what one article calls the "embryo proper" or the body of the would-have-been-born individual. One researcher tells us on the Podcast that these cells from embryos at the stage when the embryo would naturally implant are the "universal stem cells" that scientists have been searching for.

"Should Science Speak to Faith?"

That free Scientific American issue also contains a dialog between two scientists on faith, religion and the scientific community. Laurence M. Krauss and Richard Dawkins discuss their different views on engaging in "seducing" people of faith. ("Teaching is seduction." "No one appreciates a dishonest seducer.")

Gentlemen, the main point you should understand is that those of us of faith believe that science lets us understand what is - not what we should do or why.

Oh, well, at least you agree that there's a difference between right and wrong. We can begin our conversation, from this common ground.

Free Scientific American issue

2 days only, through June 30th, the new Scientific American magazine is available for download online, here.

This month's issue invites us to learn all about how humans are making global warming, about the possible effects on hurricanes, which could get stronger, how memories are laid down in the human brain, how cats evolved, and last, but not least, how to measure the impact of humans on global warming by imagining that there are no humans around at all. Of course, first, you've got to get rid of all those pesky humans.

Seriously, I expect to read these things in Analog: Science Fiction and Fact, but not in Scientific American. I could buy better graphic novels (read: comic books) if I wanted to see "what if" stories in pictures!

IVF embryo donation for destruction

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

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

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

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

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

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

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

Angina treatment from patients' own adult stem cells

Patients were given shots to stimulate the production of blood stem cells, the cells were removed from their blood - not from a bone marrow biopsy - and then injected in areas of their hearts that were alive, but not functioning.
There's more information at ScienceDaily online.
While the researchers remind us that this is a "small pilot study," I'll bet the patients who went from having chest pain when walking across the room to being able to climb stairs don't feel that it was so small!

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."