Tuesday, January 30, 2007

Texas, Adult Stem Cells, Multiple Sclerosis

Opexa is a division of Pharmafronteirs (or it's the other way around, I'm not sure) which is based at the Woodlands, near Houston, Texas.

The company specializes in cell therapies, based on adult stem cells and the controlled manipulation and replication of adult cells.

Multiple sclerosis (MS)is a disease that causes the loss of the myelin around nerves. Think of myelin as insulation that speeds the transmission of nerve signals. When myelin is lost, nerve signals can't go where they're needed, as fast as they are needed. People end up weak, with tremors, and the lack of balance, loss of coordination and the loss of the ability for the muscles that enable us to breathe and cough to function.

We know that MS is a sort of autoimmune disease in most cases. The cells that are supposed to fight infection and keep abnormal or injured cells that can cause cancer actually decide that the myelin needs to be destroyed.

For over 4 years, Pharmafrontiers or Opexa has been running a series of experiments using T cells - the specialized white blood cells that mature in the Thymus and which are supposed to kill foreign cells, like bacteria or cancer cells.

The company has a technique for isolating the patient's specific T cells that attack their myelin, growing them in the lab until they have millions, and then treating them so they can't multiply. The treated cells are then injected under the skin of the patient, and the body really notices the cells, and uses all the immune system to attack them - and all or most of the T cells in the body that act like them. So the myelin is not destroyed anymore - or at least not as fast.


Opexa are now in Phase IIb - meaning that they know it's safe to use in people (Phase I tests) and are finding out more about how much is needed and who can be helped.

There's a great first-person story about someone who is being treated as part of the experiment at "I Have MS."

For a couple of very pretty videos that explain all this much better than I ever could - and the press release by the company about the Phase IIb trial -- take a look at the Opexa site, at this page.

Added:

Opexa is selling the treatment as "Tovaxin™" - a vaccine.

That's how vaccinations work, by the way. Our bodies are convinced to make antibodies and specialized white blood cells to kill or destroy the foreign bacteria, virus -- and someday, cancer and all sorts of cells that inappropriately make those antibodies and attacks against our own normal cells, treating them as though they are damaged or foreign. As long as our bone marrow is healthy, we seem to be able to make a nearly unlimited number of those white blood cells (there's also some "depots" or reserves out in the lymph nodes and in the liver, spleen and the gut lining where the cells lurk and wait for their chance to multiply and fight disease, evidently). And I think this is how "allergy shots" work.

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Immune Privileged Cord Blood Stem Cells

Pluristem is one of the companies focusing on the commercial development of stem cells. There are two or three names which have been regularly sending out press releases concerning their research and development (besides ACT, of course).

In this case, it's a company that's marketing selected umbilical cord blood cells or placental cells. If the product turns out to be what they say it is - a population of adult or fetal cells that can be harvested from the placenta after a child is safely born, isolated by the company's secret method, and transplanted to replace or supplement diseased bone marrow - then the complication of rejection may soon be a thing of the past:

Pluristem Announces Evidence That PLX-I Cells Are Immune Privileged

NEW YORK--(BUSINESS WIRE)--Jan 29, 2007 - Pluristem Life Systems, Inc. (OTCBB:PLRS), a cell therapy company dedicated to the commercialization of stem cell products, today announced evidence that its PLX-I cells have proven to be immune privileged. PLX-I cells are Pluristem's first potential product dedicated to resolving the global shortfall of matched tissue for bone marrow transplantation by improving the engraftment of umbilical cord blood. PLX-I cells are mesenchymal stems cells obtained from the placenta and expanded by using Pluristem's proprietary 3D PluriX(TM) technology.

"Immune privileged" is defined as the absence or diminution of rejection when implanted into unmatched recipients. Being immune privileged, the PLX-1 cells carry significant positive implications in the development of Company products for a variety of degenerative, malignant and immune diseases. Additionally, this immune modulating property could prove important in treating or preventing immune reactions associated with transplantation.

Ora Burger PhD. V.P. of R&D at Pluristem states: "Our PLX-I cells possess immune privileged characteristics that can be used in the future for other applications involving transplantations. PLX-I cells posses[s] these immune privileged characteristics without carrying the associated social stigmata of embryonic stem cells because PLX-I cells come from the placenta."

William R. Prather RPh, MD, Sr. V.P. Corporate Development notes: "Mesenchymal stem cells can differentiate into a range of different tissues types associated with the musculoskeletal system such as bone, cartilage, fat, muscle, tendon and ligament. Consequently, mesenchymal stem cells are considered to be multipotent. Additionally, some reports provide evidence of these cells plasticity or the ability of mesenchymal stem cells to traverse tissue boundaries and give rise to cells of a different non-musculoskeletal tissue, such as brain or liver cells. If this is the case, mesenchymal stem cells may be used to help treat a broad range of tissues affected by damage or disease. Allogeneic transplantation of mesenchymal stem cells between different individuals may also be possible as these cells appear to be immune privileged in that they are not necessarily rejected when implanted into unmatched recipients. The characteristic of these cells being immune privileged may enable Pluristem to be involved with new clinical applications with PLX-I."

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Saturday, January 27, 2007

Of course it's fiction!

In my review of Michael Crichton's NEXT, I missed the most obvious clue that the fake news article was, indeed, fake: There's no way that the professor would have been given so much space in a review about stem cells.
(Another "Duhhh!" moment!)

Friday, January 26, 2007

Texas leads in nanotech armor

Betterhumans ("forward thinkers discussing, celebrating and creating the future") reports that another Texas researcher is a leader in biotech.

University of Texas' nanotechnologist Ray Baughman has learned to spin a new yarn from carbon nanotubules. It appears that the yarn contracts when stimulated with electricity and is expected to be strong enough to serve as armor. he has a contract with the Pentagon to produce "exoskeletons" for soldiers. More from Spiegal Online International.

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Book Review: Michael Crichton's NEXT

"Stroke Damage May Help Smokers Kick the Habit: The insula, an area of the brain largely ignored by researchers, may hold the key to breaking harmful addictions" (Scientific American Science and Technology News, January 25, 2007)

"Fresh light thrown on tragic drug trial: Animal tests may have missed danger because monkeys 'too clean'." (news@nature.com online, January 25, 2007)

"Preparing cloning for market: Ranchers are getting set, but are consumers ready?" (Boston Globe, January 26, 2007)

"Biomed firm commercializes stem-cell sales" (UPI Business Newstrack)

"New WARF Stem Cell Rules To Benefit Biotech Research" (BioWorld Headlines, AHC Media, LLC, January 25, 2007)

"Crunch time for multiple-gene tests: Sophisticated new genetic tests face an uncertain future — unless they can win clear-cut approval from regulators, insurers and, most importantly, doctors. Virginia Gewin reports." (Nature News, premium access only)

"Stem Cell Debate Rages: Effective Treatements "Decades Away" Prof. McKeown Shocks Audience" (Beaumont College Alumni News, as reported in NEXT, 2006)

Only that last headline is fictional, from Michael Crichton's newest book, NEXT.

I'm just a bit more than half-way through the book, but the fact is that I had to "Google" the fake news report to convince myself that it wasn't a very real article from some past news source. After my sureal experience of researching today's news and having to remind myself that the Google stuff was "real," I was spurred to give y'all a heads up.

Dr. Crichton is the author of The Andromeda Strain, Jurassic Park, and The Terminal Man. His science fiction is heavy on science and he has always seemed to be drawing on tomorrow's news stories - probably (I'd like to believe) because of his medical training.

This book is not very flattering to doctors. Or the media, research scientists, regulatory agencies, public policy makers or politicians. I had nearly decided that the author was stretching reality and coincidence in order to build his story, but then I opened my e-mail this morning and there were the Google News search alerts I've cited above - some of which are more fantastic than anything in the book so far.

In that "fake" news piece above, the reporter quotes a fictional professor of biology as he describes the hype that's surrounded stem cell research, including a thorough history of the human cloning scandals by Korea's Hwang Wu Suk. The "doc" continues,

". . . First, in a media-saturated world, persisitent hype lends unwarranted credulity to the wildest claims. For years the media have touted stem cell research as the coming miracle. So when somebody announced that the miracle had arrived, he was believed. Does that imply there is a danger in media hype? You bet. Because not only does it raise cruel hopes among the ill, it affects scientiest, too. They start to believe the miracle is around the corner - even thought they shourld know better.
"What can we do about media hype? It would stop in a week, if scientific institutions want that. They don't. They love the hype. They know it brings grants. So that won't change. Yale, Stanfor, and Jons Hopkins promote hype just as much as Exxon or Ford. So whenever you hear a scientist claim that his statements have been exaggerated, or taken out of context, just ask him if he has written a letter of protest to the editor. Ninety-nine times out of a hundred, he hasn't."
. . .
"Next lesson: Peer review. All of Hwang's papers in Science were peer-reviewed. If we ever needed evidence that peer review is an empty ritual, this episode provides it. Whang made extraordianry claims. He did not provide extraordinary evidence. many studies have shown that peer review does not improve the quality of scientific papers. Scientists themselves know it doesn't work. Yet the public still regards it as a sign of quality, and says, "This paper was peer-reviewed,' or 'This paper was not peer-reviewed,' as if that meant something. It doesn't.
"Next, the journals themselves. Where was the firm hand of the editor of Science? Remember that the journal Science is a big enterprise - 115 people work on that magazine. Yet gross fraud, including photographs altered with Adobe Photoshop, were not detected. And Photoshop is widely known as a major tool of scientific fraud. Yet the magazine had no way to detect it."
. . .
"The ultimate lesson is that science isn't special - at lest not anymore. Maybe back when Einstein talked to Niels Bohr, and there were only a few dozen important workers in every field. But there are now three million researchers in America. It's no longer a calling, it's a career. Science is as corruptible a human activity as any other. Its practitioners aren't saints, they're human beings, and they do what human beings do - lie, cheat, steal from one another, sue, hide data, fake data, overstate their own importance and denigrate opposing views unfairly. That's human nature. It isn't going to change."


Crichton also slams the patents on human genes and on cells that have been removed from patients in the course of medical treatment - patents that become property and make people near-property of universities and then private corporations.

(He also tweeks people like me, who love to give references in the form of urls or internet addresses in support of their points. One of the characters invents pages of "Google" references in just a few hours in order to hide her own secret. Lesson: Watch your sources, verify and then verify, again.)

Crichton is one of the writers that I recommend for what I call "ethics lessons we don't have to learn the hard way." Science fiction, which long-time Astounding Science Fiction - now Analog Science Fiction and Fact - editor John Campbell called "future fiction," often explores the "why's" and "why not's" of science, medicine and research, and the feelings that characters experience in what are (usually) novel situations that strain everyday ethics. Just as we study classical and contemporary fiction to learn more about the human condition, we can learn from science fiction authors' and their characters' reaction to what is fantastic today (but may not be tomorrow, in a few minutes, or in an "alternate history"), as well as our reaction to their reactions.

I recommend the NEXT to other SF fans and bioethics nuts. I also recently read and recommend Prey and I'm listening to State of Fear on Audiobooks. My favorites are still The Andromeda Strain and The Terminal Man, but Congo is worth reading, too.

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The future of stem cells, Texas and politics

The Friday, January 26, 2007 Austin American Statesman editorial, “Stem cell opposition could steer research away from Texas,” flatly states that Governor Rick Perry’s $3 Billion dollar cancer research initiative won't help at all if it doesn't include funding for embryonic stem cell research. The Statesman editors doubt that there will be any scientists to spend the money on.

The editorial is ridiculous – and, as the editors admit, political - in light of daily strides in ethical stem cell research and Texas’ strong research community.

Texas hospitals were among the first in the nation to offer umbilical cord blood transplants. Cooperation between Texas universities, medical schools, NASA and foreign researchers led to technology which allowed the development of embryonic-like stem cells and liver cells from umbilical cord stem cells.

Texas is already enough of a leader in ethical stem cell research to lure the President of the International Society of Stem Cell Researchers, Paul Simmons, Ph.D., away from Australia to the University of Texas Health Sciences Center at Houston.

We also have Diego Castrillon, MD, PhD., who moved from Massachusetts to the University of Texas Southwest Medical Center. Dr. Castrillon is credited with research into the "Fox O's." These are "transcription factors," or local proteins that cause the expression of certain genes. They promote the health of adult stem cells and suppress cancer cells.

This month’s issue of the journal, Cell, will include a report on further research on FoxO’s. From a press release at "Newswise"
The FoxO1, O3, and O4 transcription factors regulate genes in the complicated cell signaling network known as PI3K-AKT, or simply PI3K. Scientists have discovered that PI3K signaling is intimately involved in fundamental cell processes such as metabolism, aging, and protecting the body against cancer. The PI3K circuit has been found to be disrupted in many forms of cancer, making it a hot topic in cancer research labs and drug company boardrooms.

Based on previous work in his laboratory, DePinho, working with Diego Castrillon, MD, PhD, (who is now at the University of Texas Southwest Medical Center), determined that the three FoxOs had redundant, overlapping functions: To uncover those functions, it would be necessary to engineer mice that lacked all three FoxO transcription factors.

To make the task even more difficult, mice lacking FoxO1 die in the womb. DePinho and Castrillon had to engineer mice whose FoxO genes would function normally during development, but would contain a mechanism allowing them to be switched off in adulthood at the scientists’ will. It took DePinho’s team about two years to get the system to work, which Gilliland hailed as a “true tour-de-force of mouse genetics.”

Mutant FoxOs have been implicated in leukemia, and for Gilliland, who studies blood cancers, the triple-knockout mice were an opportunity to dig deeper into the issue. Unexpectedly, however, deletion of FoxO1, 03, and 04 caused blood cell abnormalities but not outright leukemia. A bigger surprise was that the blood stem cells “were really in trouble without those transcription factors,” he said, dividing too rapidly, losing their ability to renew themselves, and dying out. “This means that FoxOs contribute to the longevity of stem cells, and if you take them away, you dramatically shorten stem cells’ lives.”

Looking further, Gilliland and his colleagues found that the damage was being caused by reactive oxygen species, or ROS, a toxic byproduct of cells’ energy production. When the mice were treated with anti-oxidants, the stem cells regained health and longevity. “So, the FoxOs are acting as natural antioxidants,” said Gilliland. Conceivably, he added, drugs could be developed to manipulate the FoxO pathway and extend the lives of stem cells beyond their natural limits, which could aid their use in repairing diseased body tissues.


Texas' limited research funds should be spent on supporting the State's cord blood bank system and continuing research that will give us real cures for Texas' patients.

Note: First paragraph edited for grammar at 10:25 AM CST.

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Wednesday, January 24, 2007

Documentation of stem cell cancer link

From Science Daily, January 22:


U.S. scientists have clarified how normal stem cells become cancer stem cells, as well as how cancer stem cells can cause the formation of tumors.

Dr. Xi He and associate investigator Linheng Li, both with the Stowers Institute for Medical Research, studied the intestinal system in mice in which one of the human tumor suppressor genes, PTEN, had been deleted.

"We found that a loss of PTEN in intestinal epithelial cells accompanied by a loss of PTEN in stromal cells can lead to changes that may increase the number of stem cells and change their position or location," said Li. "These changes result in crypt fission and budding and can lead to intestinal polyposis and uncontrolled tumor growth."

"What we learned," added He, is that "cancer stem cells are a rare population in the tumor mass; that they are slow cycling, but more active than normal stem cells; and that cancer stem cells and stromal insertions initiate the process of primary tumorigenesis ..."

The study appears on the Nature Genetics journal's Web site.

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WARF relaxes embryonic stem cell fees and rules

The Wisconsin Alumni Research Foundation holds the patents on virtually all embryonic stem cells that have ever been produced, that ever will be produced, and of all the technological and medical results of that research. At least according to them, and at least in the United States.

And they've been sued by other researchers because of those patents - and not only because of the money involved.

However, early this week the Foundation announced that they will relax some of their earlier restrictions and that they will not charge some researchers for licensing fees. According to the Sacramento Bee,

The Wisconsin foundation that holds patents covering U.S. embryonic stem cell research will waive some of its fees to encourage more industry-sponsored research.

The changes follow criticism from scientists who said the Wisconsin Alumni Research Foundation's fees and its licensing system were driving some investment overseas.

Scientists around the country hailed the policy changes, which will let researchers share their cells for free and allow companies to sponsor research at universities without having to obtain licenses that cost up to $400,000.

"The notion of reducing fees and sharing cell lines and enabling companies to sponsor research at academic institutions is a good thing and should help push the research forward," said Brock Reeve, executive director of the Harvard Stem Cell Institute.

The Wisconsin foundation controls three patents covering research by University of Wisconsin-Madison scientist James Thomson, who in 1998 became the first to grow and isolate human embryonic stem cells. The patents are broadly written to cover the cells and research techniques used by many American scientists.


Nevertheless, the lawsuit will not be dropped, according to SignOn San Diego, by the Union Tribune
But despite the policy changes, the patent challenge will not be dropped, said Loring and John Simpson, of the Foundation for Taxpayer and Consumer rights, one of the groups challenging the patents.

“A change in licensing policy of the human ES cell patents doesn't solve the fundamental problem that the patents should not have been issued in the first place,” Simpson said. “The right thing for WARF to do is admit that it doesn't deserve the patents and abandon them in their entirety.”

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Review of Umbilical Cord Pancreas Cells

I've read the unproofed draft (their English is much better than my Korean) of "Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure" by B. Sun, et. al. (Biochem. Biophys.Res. Commun. (2007), doi:10.1016/j.bbrc.2007.01.069)

The authors do not tell us how much of the insulin-secreting cells or colonies of cells they were able to obtain. However, they do report that at one stage, the cells exhibit Oct-4 and "stage-specific antigen 4"(which are characteristic of embryonic stem cells). After inducing umbilical cord cells to revert to these embryonic-like stem cells, they then followed a previously reported protocol for inducing embryonic stem cells into beta islet cells. Colonies of cells grew in islet-like structures and were positive for both insulin and C-peptide. The C-petide is indication that the insulin came from the cells, and not from an artificial source in the nutrients in which the cells were grown.

Time will tell whether the photos are real, whether the results can be replicated in other labs, whether there are enough babies born and cord blood to be obtained to match all the diabetic patients in the world, whether it's possible to transplant immune-matched islet cell structures into humans, and whether those islet cells will survive and function in the recipients. I wonder whether the manipulated cells will be genetically stable or whether they will be prone to die or mutate.

On the other hand, if as in hematopoietic stem cell umbilical cord blood transplants, the cells do not have to be as closely matched in order to be accepted by the immune system, and if these cells persist as long as maternal stem cells have been reported to do, then this report brings us the most promising news of a possible treatment if not cure for diabetes that I've seen in all these years of stem cell reports.

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UK survey: doctors should probably kill patients

The British Social Attitudes Survey is being reported in UK papers today as "4 out of 5" and 80% of respondents feel that a doctor should be able to kill patients requesting to be killed and who are going to die anyway. The support for killing goes down if the patient is not likely to die soon of his disease or if a family member should kill the patient and for suicide with assistance from the physician.

The Guardian OnLine reports the story this way:
In a finding confirming that British public opinion is at odds with the law, today's British Social Attitudes Survey reveals strong support for euthanasia, though only in carefully defined circumstances.

Research conducted for the survey indicates that backing for voluntary euthanasia depends strongly on whether someone is terminally ill, on levels of suffering and on how death occurs. There is much greater support for a doctor being permitted to end someone's life rather than a relative, or than suicide assisted by a doctor.

Strongest support - from 80% - came for the suggestion that a doctor should "probably" or "definitely" be allowed by law to end the life, at the patient's request, of an individual with an incurable or painful illness from which they will die, such as cancer.

Seventy-five per cent backed doctor-administered euthanasia for those with an incurable and terminal illness who say their suffering is unbearable.

However, public support for euthanasia drops dramatically for cases where an individual is not already facing death as a result of their condition. Where the patient has an "incurable and painful illness, from which they will not die", 45% support assisted dying, while only 43% back euthanasia for those not in danger of death but permanently and completely dependent on relatives.

When questioned on a specific condition, public backing falls still further. Exactly a third of people said they would condone euthanasia for individuals with an incurable and painful but not terminal illness, such as severe arthritis.


From the (Scotland) Herald:
VOLUNTARY euthanasia for terminally ill patients is supported by eight out of 10 people in Britain, according to the latest survey of social attitudes.

Professor Sheila McLean, of Glasgow University, and a team of researchers from the National Centre for Social Research investigated attitudes towards assisted dying and found a large majority were in favour if doctors were in charge of the procedure.

The British Social Attitudes Survey found 80% supported voluntary euthanasia for "a person with an incurable and painful illness, from which they will die, for example someone dying of cancer".
continued...

There is less public support in cases where a person will not die from their incurable illness, with only 45% found to be in favour.

A similar proportion supported the right to die for someone who is completely dependent on relatives for washing and feeding but not in pain or danger of death.

Euthanasia by a doctor attracted the most support - 80% - while physician-assisted suicide was supported by 60% and slightly less than half said relatives should be allowed to administer voluntary euthanasia. A link between religion and attitudes towards assisted death was found with support waning among regular worshippers.


Times Online coverage is not nearly as informative as either of the above sources, but it's available here.

Each of the articles review recent attempts to legislate in favor of euthanasia and notorious cases that have been in the news.

Thanks to Matthew Eppinette, again.)

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Insulin from Umbilical Cord Cells

Another lead from Wesley Smith and Matthew Epinette at Bioethics.com on a report that Korean researchers have reported in the Korean Times that they will soon publish that they have produced beta islet insulin producing cells from umbilical cord blood. The abstract of the unproofed "in press" article is free here, at the website of the Biochemical and Biophysical Research Communications. You can also purchase access to the unproofed article.

Reference:
"Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure." Bo Sun, (a,b), Kyung-Hwan Roh (a,b), Sea-Rom Lee (a,b), Yong-Soon Lee (a) and Kyung-Sun Kang (a,b). (a)Laboratory of Stem Cell and Tumor Biology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea; (b) Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, South Korea. Biochemical and Biophysical Research Communications doi:10.1016/j.bbrc.2007.01.069
Article in Press, Uncorrected Proof

Received 29 December 2006. Available online 24 January 2007.

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Mothers keep on giving

Stem cells, that is.

We have further proof of yet another naturally occuring adult stem cell line that contributes to treatment of diabetes in the recipient long after introduction of the cells and without immune rejection.

Scientists have reported in the "Proceedings of the National Academies of Science (Free abstract) about the discovery that mother's stem cells may cross the placenta and that- in those babies who grow up and later develop Type I diabetes ("Juvenile Diabetes," or "Insulin Dependent Diabetes Mellitis") - some of those cells help repair the pancreas and make insulin.

The researchers thought they would find evidence that the maternal cells might actually cause the diabetes, but instead found that the maternal cells had become beta islet cells of the pancreas, the cells which produce insulin, and were functioning in a beneficial way, years later.

From the online journal, ScienceDaily,

For the first time, scientists have discovered that cells passed from mother to child during pregnancy can differentiate into functioning islet beta cells that produce insulin in the child. The same study also found that maternal DNA was found in greater amounts in the blood of children and young adults with Type 1 diabetes than their healthy siblings and a control group, implying that they may be attempting to repair damaged tissue.
The findings suggest a beneficial role for this type of maternal microchimerism. Microchimerism is the term used when an individual harbors cells or DNA that originate from another genetically distinct individual.

In this study, published in the Jan. 22 issue of the Proceedings of the National Academy of Sciences, J. Lee Nelson, M.D., a member of the Clinical Research Division at Fred Hutchinson Cancer Research Center, and colleagues found no evidence that the mother's cells were attacking the child's insulin cells and no evidence that the maternal cells were targets of an immune response from the child's immune system.

"We think the maternal cells may be helping to regenerate damaged tissue in the pancreas," Nelson said.

She said investigators are excited about new possible approaches to treat Type 1 diabetes raised by their findings. For example, if maternal microchimerism results in cells that make insulin, a mother's stem cells might be harvested and used to treat her diabetic child. Such cells would have a genetic edge over donated islet cells from a cadaver that are usually completely genetically mismatched.

"The child is probably tolerant to the mother's half-matched cells because the child acquired the cells during its life as a fetus while its immune system was still developing," Nelson said.

Originally, the study of 172 individuals and pancreatic tissue from four males was designed to ask the question whether these small numbers of maternal cells might be involved in any way in Type 1 diabetes. "My initial theory was that perhaps, in some situations, too many mother cells cross over to the fetus at the wrong time, becoming beta cells that make insulin in the child. Could diabetes result because the child lost tolerance to those cells because they are genetically half foreign? Our research disproved this," she said.

Instead, the researchers found a small number of female islet beta cells in male pancreatic tissue (procured from autopsies) that produced insulin. "To our knowledge a maternal contribution to endocrine function has not previously been described," the authors said. "Our findings also raise the possibility that naturally acquired microchimerism might be exploited to therapeutic benefit."

The study found significantly higher levels of maternal DNA in the peripheral blood of 94 children and adults with Type 1 diabetes as compared to 54 unaffected siblings and 24 unrelated healthy subjects they studied. Maternal microchimerism first was recognized in children with severe combined immunodeficiency in the 1970s. In 1999, a study by Nelson et al was first to show that maternal microchimerism persists into adulthood for persons with uncompromised immune systems
(Journal of Clinical Investigation 104:41-47).



Researchers in the UK also contributed to the report. From the BBC:

Jo Brodie, of the charity Diabetes UK, said scientists trying to perfect islet cell transplantation as a treatment for diabetes faced problems sourcing enough material, and preventing the recipients' immune systems from attacking the newly transplanted cells.

"If cells with the potential to produce insulin can pass from mother to child during pregnancy, without the child's immune system destroying them as seems to be the case here, then this could open up promising new avenues of research, and perhaps provide a new source of insulin-producing cells for therapeutic use."


(That 1999 article is available free online at PubMed Central: "Microchimerism of maternal origin persists into adult life." Maloney S, Smith A, Furst DE, Myerson D, Rupert K, Evans PC, Nelson JL.J Clin Invest. 1999 Jul 1; 104(1): 41-47.PMCID: 408407.)

Where did the stem cells come from in the mother? How are they preserved in the child through the years, even when mom and child would not be considered a good "tissue match" for organ donation? And how are they stimulated and recruited to the necessary tissues and organs in order to contribute to the repair and function of the child's tissues? How can we mimic and maximize the process when and where we want?

All of these questions are fertile ground for research. And not a one of the answers will depend on the destruction of a human being.

There's coverage in the January 22 Washington Post. However, the article states that Type I diabetes is inherited. The tendency may be inherited, but I don't believe that anyone has determined the actual gene or any specific trigger that can be said to cause Type 1 diabetes, other than the patiint's own immune system begins to make antibodies against the beta islet cells and insulin. Somehow, the mother's cells aren't affected in this case - which makes the discovery even more important and hopeful for patients: there has always been the concern that any new stem cells introduced into the patient would also be subjected to attack.

More information on Type 1 diabetes at E-Medicine.com (a very reliable site for medical information) and from The American Academy of Family Physcians. That last link is courtesy of the Post.

Hat Tip to Wesley Smith and Matthew Eppinette at Bioethics.com (as well as my Google News Search alerts).

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Monday, January 22, 2007

Follow the DNA trail - "superbugs"

Google News search alerts sent me to Weazlesrevenge blog, and an article originally published in (of all places) WIRED magazine about resistant strains of Acinetobacter baumannii that - it turns out - moved from European hospitals back to the war zone in Iraq.

Since biochemistry in college, I've never been able to figure out why E. coli hasn't wiped us all out. E. coli, the bacteria that normally makes up the bulk of the intestinal contents and which causes disease when people are exposed to a new strain, is able to exchange genetic information with other bacteria in just about every way possible. E. coli is the reason you're told "don't drink the water" in some countries and remember the spinach?

It appears that one of the strains of Acinetobacter that has been a deadly problem for our soldiers injured in Iraq (reported by Forbes magazine in 2005) is another adaptable bacteria:
When a team of geneticists unlocked the secret of the bug's rapid evolution in 2005, they found that one strain of multidrug-resistant Acinetobacter baumannii carries the largest collection of genetic upgrades ever discovered in a single organism. Out of its 52 genes dedicated to defeating antibiotics, radiation, and other weapons of mass bacterial destruction, nearly all have been bootlegged from other bad bugs like Salmonella, Pseudomonas, and Escherichia coli.


At first, it was assumed that the bacteria came from the dirt and dust in the field in Iraq, resulting in contamination of war-zone hospitals and moving on to the secondary evacuation hospitals and eventually back to the US. Instead, DNA infectious disease detectives discovered that the germ originated in Europe and moved to the Iraqi hospitals by hitchhiking on medical personnel and equipment.


Little packets of circular DNA called "plasmids," protected packets called "phages," and even loose DNA in the environment, allow the exchange of information between one individual bacterium and another. Here and here are sites that explain the processes in more detail. And it may have you looking at that raw fruit or vegetable or the funny spot on the bread a little differently.

Never fear, the WIRED author tied the bacterial infection in with high tech informational nature of the magazine. I appreciate the twist on words:
In the open source world of bacteria, everyone is working for the resistance. Ramping up the immunity of any single organism, while dramatically increasing the size of the population most susceptible to infection, only helps the enemy. To an aspiring superbug, war is anything but hell.

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Website update and event announcements

I've updated the "News and Events" page at LifeEthics.org to include pictures from testimony to Texas Legislators in September of last year. (There are grand daughter pictures!)

I haven't figured out how to get a decent calendar for the site, yet. The current version of the site is built using Microsoft Publisher, but I'm learning - or trying to learn - how to use the new Expressions Web.

However, I have been invited to speak on Bioethics in Texas Legislation and Policy at two meetings in the next few weeks. I'll be at my "hometown" Comal County Republicans on January 30th and then at the Texas Republican Assemblies annual meeting in Austin, Texas on February 17th.

(In order to maintain my non-partisan standards, please note that the first event documented at LifeEthics was for the annual convention of the Texas "Democrats for Life.")

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Nanofiber Scaffolds for Neural Stem Cells (and some truth)

Johns Hopkins researchers report that they have developed "nanofibers" impregnated with special proteins which allow them to grow neural stem cells from embryonic stem cells without "requiring high concentrations of growth factors."

One of the researchers, Neuroscientist Hongjun Song, comments on the immediate results of the research, which will not include actual patient therapy:

“Eventually, stem cells will be very important for treating disease using cell replacement therapy, but more immediately stem cells offer the opportunity to model human disease and find ways to screen for therapeutic drugs to treat the disease.”


Song is a member of the body which oversees stem cell research at Johns Hopkins, the "Stem Cell Policy and Ethics Program." This means that even though he has a vested interest in maintaining his own lab and promoting his research, he is among those at Johns Hopkins who determine how to follow the institution's mission:
  • Facilitate the ability of the public to benefit from advances in cell engineering in morally responsible ways;

  • Anticipate moral and policy challenges in stem cell science and cell engineering; and

  • Provide opportunity for careful and interdisciplinary analysis of these challenges that will be of assistance to both policymakers and the public.


The inclusion of Song in justifying and lobbying for his own work under the guise of "ethics" is a serious conflict of interest and can not be called "morally responsible."

The good news is that some people see an end to the use of embryo destruction. From the article posted earlier today on trading eggs for in vitro fertilization fees:
In any case, the need for eggs may only be temporary.

They are, in fact, only a tool to reprogram the inserted DNA so that it will drive the development of an early embryo. Scientists hope to learn enough about that reprogramming process to let them take an ordinary cell from a person and use it to produce other kinds of cells, perhaps without going through an embryo stage. That might happen in 10 years, Murdoch estimated.

And then they wouldn't need eggs any more.

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Sunday, January 21, 2007

Trading eggs for fertility treatment

Women who are desperatly trying to get pregnant, but who cannot afford to pay $5,000 - $6,000 for in vitro fertilization may be offered lower IVF fees in exchange for donation of some of their oocytes for research in the UK. The Human Fertilization and Embryology Authority approved the trades for one lab last July, but are now seeking public comment, according to an Associated Press article.

The limiting factor for embryonic stem cell research has never been the restrictions placed on US Federal funding. The problem is obtaining eggs from women.

So far, the track record for altruistic donations is mixed. On one hand, hundreds of women volunteered to donate eggs in South Korea for research by the now-disgraced scientist Hwang Woo-suk, who fraudulently claimed success in therapeutic cloning.

But Dr. Robert Lanza, vice president of research and scientific development at Advanced Cell Technology Inc. of Alameda, Calif., said he has given up trying to get donations without compensation. After more than a year of pursuing that strategy and about 100 advertisements, ACT was able to get only one woman to donate eggs, he said in an e-mail.

And Kevin Eggan of the Harvard Stem Cell Institute, who's been seeking eggs since May in return for reimbursing out-of-pocket expenses, said recently that the effort had generated some calls but no donors yet. The approach must be given more time to work, he said.

Murdoch, who also directs a fertility treatment center in Newcastle upon Tyne, said that when her lab asked fertility-clinic patients to donate eggs, it received only 66 over seven months. That's just not enough, she said.

In contrast, if her new plan attracts two women a week — chosen because they appear likely to produce lots of eggs — it would provide 20 eggs each week. That's still not a lot, but the supply should be steady, she said.

Her "egg-sharing" plan resembles an arrangement that's used occasionally at fertility clinics. In that plan, a woman shares her eggs and treatment costs with another woman who wants a baby.

Murdoch's group has permission from Britain's Human Fertilization and Embryology Authority to set up the arrangement for stem cell research. Now it's a question of raising money to finance it. Murdoch said she hopes to start offering the deal to British women in a few months, and that she has already heard from dozens of women eager to participate.

Though the HFEA approved Murdoch's plans in July, it has since started gathering public and expert opinions on whether egg sharing should be permitted. "If the consensus is that this is not a good idea, we can change the policy, and rescind the license," said John Paul Maytum, an HFEA spokesman.

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Friday, January 19, 2007

Proof there's no stem cell "ban"

Wesley Smith, at his blog Secondhand Smoke, notes that American Cell Technology has received a grant from the National Institute of Health for research on embryonic stem cells. He also points out what should be obvious: ACT must have received this funding for research on the stem cell lines that are authorized under President Bush's August, 2001 policy.

(In case you can't remember who ACT is, they're the organization that claimed to have cloned human embryos back in 2001, and who claimed to have found a way to produce embryonic stem cells without killing the embryo when in fact they killed every one of those human embryos they used. The company is one of the best examples of the sort of ethics that make people like me think of "ethics for sale." ACT has employed ethicists Art Caplan and Glenn McGee and is very closely associated with Geron, WARF (the research foundation at the University of Wisconsin).

So much for the myth that these cells can't be used or that there is any sort of "ban."

The focus of the research is basic research on how Embryonic Stem Cells divide and differentiate.

From the Washington Business Journal:
The money will support an ongoing collaboration between Alameda-based Advanced Cell (OTCBB: ACTC) and The Burnham Institute of Medical Research in La Jolla.
Researchers are investigating the genetic mechanisms and proteins believed to control how basic embryonic stem cells develop and differentiate. That understanding is essential in harnessing the regenerative powers of stem cells in medical applications, the company says.


This is very basic research, not an actual attempt to produce cells for use in treatments. Hopefully, the added knowledge will point to ethical, non-destructive ways to obtain stem cells for treatment in actual patients.

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Support science and human rights for all

That's the point that Yuval Levin makes in his New York Times op-ed piece (free registration required), "A Middle Ground for Stem Cells," today. The essay is also available online at the International Herald Tribune.

It is, to begin with, not about stem-cell research, any more than an argument about the lethal extraction of livers from Chinese political prisoners would be a debate about organ transplantation. There are ethical and unethical ways to transplant organs, and there are ethical and unethical ways to conduct stem cell research. The question is to which category a particular technique — the destruction of living embryos for their cells — belongs.

The debate is also not about whether there ought to be ethical limits on science. Everyone agrees there should be strict limits when research involves human subjects. The question is whether embryos destroyed for their cells are such human subjects.

But that does not mean the stem-cell debate is about when human life begins. It is a simple and uncontroversial biological fact that a human life begins when an embryo is created; its human life will last until its death, whether that comes days after conception or many decades later.

But that does not by itself settle the ethical debate. The human embryo is a human organism, but is this microscopic being — with no self-awareness and little resemblance to us — a person, with a right to life?

Many advocates of embryo-destructive research argue that the human embryo is just too small, too unlike us in appearance, or too lacking in consciousness or sensitivity to pain or other critical mental capacity to be granted a place in the human family.

But surely we have learned the hard way not to assign human worth by appearances. Surely we would not deny those who have lost some mental faculties the right to be regarded with respect and protected from harm. Why should we deny it to those whose faculties are still developing?

At its heart, then, when the biology and politics have been stipulated away, the stem-cell debate is not about when human life begins but about whether every human life is equal. The circumstances of the embryo outside the body of a mother put that question in perhaps the most exaggerated form imaginable, but they do not change the question.

The evidence of nature sometimes makes it very hard to believe that all human beings are equal. It takes a profound moral case to defend the proposition that the youngest and the oldest, the weakest and the strongest, all of us, simply by virtue of our common humanity, are in some basic and inalienable way equals.

Our faith in that essential liberal proposition is under attack by our own humanitarian impulses in the stem-cell debate, and it will be under further attack as biotechnology progresses. But the stem-cell debate, our first real test, should also be the easiest. We do not, at least in this instance, face a choice between science and the liberal society. We face the challenge of championing both.

President George W. Bush's stem cell policy seeks to meet that challenge. It encourages scientists to pursue the cells they seek without destroying life.


Please consider reading the rest at one of the links above.

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Calling all scientists

The Aspen Ideas Festival is a meeting that I had never heard of until recently (I actually found it Googling for "Bioethics and Politics" and "Bioethics and Policy" which are names I've come up with for alternative blogs in case I decide to change my focus) There are audio recordings and transcripts online which contain segments that should be fascinating to many of us, whether our primary interest is religion, politics or bioethics.

If you want to see who are considered the elite thinkers in this country - at least by others who consider themselves elite thinkers - take a look at the website and listen or watch some of the sessions from the July, 2006 event.

One segment is audio-only, "Politics and technology." Nigel Cameron links to it on his blog, and he was the sole prolife member of the panel. Other panel members include Neal Lane, a professor of Physics and Astronomy at Rice University at Houston, Texas and Assistant to the President for Science and Technology and Director of the White House Office of Science and Technology Policy from 1998-2000, Doroth Shore Zinberg, a sociologist and lecturer in Science, Technology and Public Policy at Harvard, and Lawrence Krauss, a professor in Physics and Astronomy who has written The Physics of Star Trek.

The one thing that all of the panelists agreed to in the very enlightening hour and a half, is that all of us should become involved in policy making, whether it's in politics, our professional associations, or in teaching about science and ethics in our local communities and churches. I love it when people so much more brilliant than I agree to even part of the mission and vision that I wrote for LifeEthics:


We encourage all of our members, especially medical and scientific professionals, to become involved in setting the policies of their communities, associations, schools and businesses in order to ensure that those organizations maintain high ethical standards.

We educate the public and professional communities on current events concerning the right to life and liberty of humans. Our members mentor one another in opportunities to serve in professional and academic capacities to fulfill our mission. We monitor and alert our members and the public about unethical scientific research and medical therapy. We are active in our own institutions and associations in order to influence the policy decisions of the organizations that represent us.

We use standard scientific and medical definitions and verifiable scientific data whenever possible in our position statements and deliberations and expert opinions only when the evidence is not available.

(The full panel would not be in agreement with the section that is struck.)

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Thursday, January 18, 2007

David Prentice's Science rebuttal

This week, Science Magazine, has published a Letter to the Editor (sorry, subscription only) by David Prentice, Ph.D., in response to the letter by Smith, Neaves and Teitelbaum from last July.
(That was the letter which prompted Michael Fumento to dub the Journal "PseudoScience.")

In his letter, Dr. Prentice points out that the "Supporting Online Material" from the first letter actually contradicted the accusations of the three.

Will we have a series of rebuttals to the rebuttals, now?

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Bioethicists aren't needed

Well, they didn't come right out and say it.

Moreno and Berger are still stomping their feet at Ramesh Ponnuru for doing his job. After all, he's an editor for a magazine covering "Republican/conservative news, commentary, and opinion."

Moreno has a Ph.D. in philosophy, and Berger is an Assistant to Moreno and two other Fellows at the socialist "Center for American Progress Institute for Bioethics. I suppose that it could be said that they are doing their jobs, too, except for the way they argue their point.

They argue that scientists and the "scientific community" do not recognize that there are "viable alternatives" to embryonic stem cells. Because they are certain of this opinion, they have attacked a report that proposes research "Without Destroying Human Life."

If these two bioethicists are so certain that that scientists are the final authorities as to what should be done, what is their justification for "bioethicists" (other than to make arguments for the scientists who lead them, that is)?

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Progressives vs. Conservatives (rubber, glue)

What did I tell you? I forgot to tell you what the "Progressives" fuss was about and to link to the actual articles. Which meant that I didn't review the actual critiques of the report by the President's Domestic Policy Council (covered here, last week).

Jonathan Moreno and Sam Berger of the Center for American Progress' Bioethics Project wrote "Alternative Sources of Stem Cell Truth: White House Misrepresents Potential of Alternative Sources of Pluripotent Stem Cells" on January 11th. Ramesh Ponnuru critiqued their critique in "Selling Alternatives Short: Good news for humanity is bad news to some" at the National Review OnLine. Moreno and Berger wrote a rebuttal, "Shouting Semantics Over Science."

It's easy to dismiss the fussin' as political differences or competition between rival publications (although I doubt that NRO has much to worry about). However, what is at stake is the very basis of ethics, itself: the primary philosophical questions "who am I, why am I here, what should I do?"

There's also the secondary question, "how can I keep that other guy from killing me?"

Some of us believe that it is never ethical or permissible to destroy human embryos, even if it means that we never obtain the treatments that Moreno and Berger mention in their first article. Moreno and Berger believe that research should not be hampered by concerns for human embryos, even though every single possible therapy that they mention is just as likely to come from non-destructive therapy. (anyone who doubts that there is already research supporting non-destructive sources for each and every line M & B mention can try PubMed, review this blog, or email me for the address where they can send their self-addressed stamped envelope and payment for the hard copies of the pertinent research.)

It's true that I agree with Ponnuru,
Again and again, this duo treats readers to double standards. Alternative approaches can be dismissed whenever promising findings haven’t been reproduced; but findings favorable to embryonic stem-cell research are taken to the bank, whether or not they’re reproduced. The long-term potential for embryo-destructive research is emphasized; the failure of alternative approaches to produce immediate results is held against them. Data is cherry-picked to show that the absence of taxpayer funding for embryo-destructive research has hurt American competitiveness; contrary evidence is ignored.

One of the great fake bits of data in this debate — the “400,000 excess embryos stored in fertility clinics” — makes a return appearance. To repeat: We know that number from a study that also showed that fewer than three percent of those embryos would be available for research.


Let's face it, the goal of all stem cell research is to manage functioning tissue, organs, and cells. These are made by adult stem cells. The embryonic stem cells and even the fetal/amniotic/placental stem cells are more primitive or intermediate forms of stem cells similar to the the Multipotent Adult Progenitor Cells (MPACs), not the specific stem cells or stem cell lines that are desirable for in vivo use. Animal models, umbilical cord, amniotic/placental, and MPACs, along with our experience with actual adult stem cells should be sufficient, without killing human embryos, without creating new embryos for destruction, and without cloning or creating animal-human hybrids.


Besides, the true goal should not be the ability to implant actual cells and organs, except in dire emergencies - what we really want is to be able to regenerate our heart, brain, kidney, pancreas and skin cells in place, as we lose or injure them.



HT to Jivin' Jehosaphat

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Biased bioethicist's slip is showing

Every time I note someone else's editorial or grammatical mistakes, I (later, of course) find that I've made some glaring mistake of my own in that comment. I'll try to avoid that here, but read closely, just in case.

Nevertheless, . . .

Bioethics.net, the blog of the editors (and pseudoeditors) of the American Journal of Bioethics, a couple of especially snide, petty and biased comments, today.

If you could identify with anyone called a "mouth breathing Pentecostal," don't read the first (which I believe is a rant from authored by Art Caplan) concerning the ensoulment of cloned humans (my previous discussion is here) unless you can brush off the insult. (However, perhaps someone who does read it could tell me how the editors and pseudoeditors (e&p) could believe that Ben Franklin "wouldn't have allowed a column as dumb as Answer Fella to exist in the first place.")

In my own snide, petty manner, I'm copying