Friday, April 17, 2009

Study of iPS cells draws nearer to finding cures

Research in stem cells and the origin and treatment of disease is definitely moving away from destructive embryonic stem cell research toward induced pluripotent stem cells (iPS).

A fantastic review that connects Japan's Dr. Yamanaka, San Francisco's Srivastava, the University of Texas Southwestern Medical Center in Dallas, and the Burnetts of Sulphur Springs, Texas, is published in the Japan Times. (Written by Rob Waters for Bloomberg news.)

Yamanaka, a professor at Kyoto University, developed a technology that may make the argument moot. Yamanaka, who has two daughters, started his effort 10 years ago, after peering at a tiny embryo through a microscope and reflecting that it might form a child if it wasn't used to make stem cells, he said in an interview.

"That's the moment I thought about this project," he said. "I saw that if we could make pluripotent stem cells without using human embryos, that would be ideal."

In 2006, he scored his first success. Using a virus to insert four genes into the skin cells of mice, he started a process that returned the cells to a primordial state able to form any other cell in the body. Yamanaka named them induced pluripotent stem, or iPS, cells. The next year, he repeated the feat with human cells.

Yamanaka and researchers elsewhere are now racing to find better ways to achieve the same effect. They would like to get rid of the virus, which can cause the genes to lodge permanently in the structure of the cell and may trigger the growth of tumors.

Yamanaka's technique exploits a basic fact of human biology — that every cell in a person contains the genetic instructions that set that person's traits, from hair color to inherited disease. By taking skin cells from a person with a disease and turning them into cells in the heart, brain or pancreas that are affected by a genetic disease, researchers can experiment with disorders at their earliest stages, Harvard's Melton said.

Labs are now creating iPS cells because making them is far simpler than getting cells from embryos, said Jeanne Loring, founding director of the Center for Regenerative Medicine, part of the Scripps Research Institute in La Jolla, Calif.

"Every stem-cell researcher I know has made about a dozen," Loring said.

She estimates that researchers have made 300 different so-called lines of iPS cells, a number that may double this year. Each line is a colony of cells descended from the first ones made. Scientists keep them alive in culture and the cells keep replicating.

Grants of $23 million awarded last June by the California Institute for Regenerative Medicine, the state's stem-cell funding agency, show that researchers are embracing iPS cells. Of 16 grants awarded, eight went to teams developing new iPS cells and five to groups comparing iPS and embryonic cell types. Just three went to scientists proposing to work solely with embryonic cells, according to the San Francisco-based agency.
(Emphasis mine.)


And actual treatments are coming soon:

In 2004, Srivastava, then working at the University of Texas Southwestern Medical Center in Dallas, went with colleagues to Sulphur Springs, Texas, to collect blood samples and perform ultrasound scans on members of the Burnett family.

The researchers analyzed the genes of family members and found that 11 had heart-valve defects linked to mutations in a gene called Notch1, which plays a role in the formation of many organs, including the heart.

People with this mutation make half as much of the Notch1 protein as they should and their heart valves develop abnormally. The protein shortage primes their valves to take on extra calcium, which, over time, makes them stiffen, malfunction and require replacement.

Four years after his Notch1 discovery, Srivastava, now the director of the J. David Gladstone Institute of Cardiovascular Disease, supervised as the Burnetts had a pencil-shaped skin punch pushed into their calves to extract a bit of skin. When the boy's turn came, his 12-year-old brother, Ryan, laid a comforting hand on his back.

The iPS cells made from the Burnett's skin will be coaxed to become heart cells that carry the Notch1 mutation, Srivastava said. He plans to use the cells to test for drugs that boost levels of the Notch1 protein. This, he reasons, should make the hearts of people like the Burnetts more resistant to the entry of calcium and reduce the mineral's buildup on the valves.

A drug that could do this may essentially prevent the disease, Srivastava said. That is because the condition is present at birth, yet symptoms usually take decades to develop, giving a medicine ample time to work.

Within five years, Srivastava predicts, he will have found the right drug and be ready to start human clinical tests. A closely held company named iZumi Bio Inc., in California, will collaborate with Srivastava on this and other research involving iPS cells, Seidenberg of Kleiner Perkins said.

Thursday, April 16, 2009

Texas Medical Association doesn't support conscience

This TMA press release/"Alert" is a shallow statement which ignores the history and facts behind the ruling and addresses the right to conscience as though it is dependent on circumstances and can be "rescinded."

The individual right not to act is called "Liberty." As an inalienable right, liberty cannot be given away or taken. It cannot be "balanced" by actions of the State or by organized medicine, only infringed.

The ruling does cover emergencies and is only a clarification of the many laws in place at this time to protect the right not to act of health care professionals.

Was there any attempt to balance this opinion by contacting those in support of the ruling?

For more information on the Ruling and the (4 year or more) history behind it, see the many "conscience" articles at this blog and the information at Freedom2Care.

From the Texas Medical Association:



TMA Backs Rescinding 'Conscience' Rule


TMA, AMA, and state medical societies across the country support the Obama administration's plan to rescind a federal rule that prohibits recipients of federal funds from forcing physicians and other health care professionals to participate in actions they find religiously or morally objectionable.

In a letter to Acting Health and Human Services (HHS) Administrator Charles E. Johnson, the groups said the Conscience Rights of Health Care Providers regulation, adopted by the Bush administration in December, is unnecessary and could have far-reaching implications. They said it "could undermine patients' access to vital medical care and information, impede advances in biomedical research, and create confusion and uncertainty among physicians, other health care professionals, and health care institutions about their legal and ethical obligations to treat patients."

They wrote that they support "strong conscience protections" for physicians, residents, and medical students and other health professionals, especially when it comes to abortion. No physician, hospital, or hospital employee should be required to perform an act that violates good medical judgment or personally held moral principles. "However, while we support the legitimate conscience rights of individual health care professionals, the exercise of these rights must be balanced against the fundamental obligations of the medical profession and physicians' paramount responsibility and commitment to serving the needs of their patients. As advocates for our patients, we strongly support patients' access to comprehensive reproductive health care and freedom of communication between physicians and their patients, and oppose government interference in the practice of medicine or the use of health care funding mechanisms to deny established and accepted medical care to any segment of the population."

Other points in the letter include:

* Abortion education should be encouraged "so medical students receive a satisfactory knowledge of the medical, ethical, legal, and psychological principles associated with termination of pregnancy …" The letter adds that "the observation of, attendance at, or any direct or indirect participation in abortion should not be required." Resident training should include "specific educational standards for the knowledge and skills associated with pregnancy termination that allow an exclusion for individuals or residency programs with religious/moral objections or legal restrictions."
* Several provisions and definitions in the rule "are ambiguous, overly broad, and could lead to differing interpretations causing unnecessary confusion among health care institutions and professionals, thereby potentially impeding patients' access to needed health care services and information." The rule, for example, defines "health service program" as "any plan or program that provides health benefits, whether directly, through insurance, or otherwise, which is funded, in whole or in part" by HHS. "This definition inappropriately expands the scope of the conscience provisions beyond family planning and abortion services to include virtually any medical treatment or service, or biomedical and behavioral research," the letter says.
* The rule does not address how conscience rights of individuals and institutions apply in emergencies.

Wednesday, April 08, 2009

Austin, Tx., Judge allows mother to harvest dead son's sperm

This story illustrates the outcome of autonomy and "because we can."

How awful for this woman to lose her son in this way. However, I'm not sure that a child should be born - conceived - in such a way. Certainly not as a "grand child," rather than a child born for his or her own being. I hope the mother takes a while to consider her actions, her ability to raise this child and to love him or her for himself/herself, rather than as a memorial to her dead son.

(On the other hand, humans are pretty adaptable, maybe this child won't suffer at all. How many of us felt that we were "means to an end" for our parents at some time?)

From the Austin American Statesman (where stories tend to disappear after a time), :

TRAVIS COUNTY COURTS
Judge OKs collecting of dead son's sperm
Mother of man who died after Sixth Street attack wants to try to have grandchildren.

By Tony Plohetski
AMERICAN-STATESMAN STAFF
Wednesday, April 08, 2009

The mother of a 21-year-old assault victim who died of his injuries received permission Tuesday for his sperm to be collected post-mortem, giving her the chance to have a grandchild through a surrogate mother.

Travis County Probate Judge Guy Herman ordered the medical examiner's office to maintain the body of Nikolas Colton Evans until his sperm can be taken.

Herman also said officials at the office must provide access so an expert can take the specimen.

Herman issued the orders after an emergency hearing at the request of Marissa Evans, whose son died Sunday after being punched and falling during a March 27 assault on East Sixth Street.

"I want him to live on," Evans said. "I want to keep a piece of him."

She said that her son had frequently talked about his desire to have three sons and had chosen their names: Hunter, Tod and Van.

Marissa Evans and her attorneys were trying Tuesday to find a urologist or other medical expert willing to collect the sperm. According to medical experts and published reports, whether such sperm is useful often depends on how quickly it is collected after death.

University of Texas law professor John Robertson, who specializes in bioethics, said that state law gives parents control over a child's body for donation of organs and tissues but that "this use is very unclear."

"There are no strong precedents in favor of a parent being able to request post-mortem sperm retrieval," he said.

Police have said Nikolas Evans was leaving a bar with a friend about 2 a.m. last month when they got into an argument with several men.

After that argument, police have said, another group approached Evans and his friend, and one of the men in that group hit both of them. Evans hit his head on the ground after he was punched, according to investigators.

No arrests have been made in the case.

Evans was taken to University Medical Center at Brackenridge, where he remained until his death.

Marissa Evans, who donated her son's organs, said she repeatedly asked whether his sperm could be taken during the donation process Monday but was told it was not possible.

Michelle Segovia, spokeswoman for the Texas Organ Sharing Alliance, said the organization deals in procuring major life-saving organs but provides families with information about a company that performs sperm collections.

She said the organization has gotten three or four such requests in recent years.

Evans said she was unable to find someone to collect the sperm Monday. Early Tuesday, she contacted Austin attorney Mark Mueller and asked whether he could help her file court papers to seek her son's sperm.

"I can understand her situation," Mueller said. "She has just lost her son, and she knew her son wanted to have children."

Mueller said he asked Herman for an emergency hearing, after which the judge granted the request.

"His mother wanted it done," Herman said. "There were other body harvesting that was going to take place, and I didn't see why this additional body harvesting shouldn't take place."

According to court documents, donation workers began taking Nikolas Evans' organs at noon Monday and continued until 9 p.m., at which time he was removed from life support.

Court documents said that it was essential for Evans' sperm be collected within 24 hours of him being removed from life support unless his body were cooled to no more than 39.2 degrees. Herman said the body is being kept at the appropriate temperature.

"Irreparable harm will be caused by the failure to harvest the sperm prior to that time," documents said.

Attorneys representing Marissa Evans had initially asked that the medical examiner's office collect the specimen, but Herman said the agency wasn't equipped to do so.

Dr. Elizabeth Houser, a urologist for the Urology Team in Austin, said she is familiar with a case in which a man's sperm was collected 30 hours after his death and stored for 15 months before a woman was inseminated.

Evans, who also has a 22-year-old son, described Nikolas Evans as a quick-witted aspiring filmmaker who recently had been accepted into film school at the University of California at Los Angeles.

A memorial service is set for 2 p.m. Saturday at Shepherd of Life Lutheran Church in Arlington.

"He was just a pleasure to know," Marissa Evans said. "It was evident in the fact that at any given time, there were 15 to 20 kids at the hospital waiting to see if he was OK.

"He was just an all-around good kid."

Wednesday, April 01, 2009

HPV Vaccine works for males

Good news from the Family Practice News:

ATLANTA — The human papillomavirus vaccine was efficacious in preventing persistent infections and genital warts caused by HPV strains 6, 11, 16, and 18 in a Merck-sponsored study of 4,065 males aged 16-26 years.

The findings were presented by Dr. Richard M. Haupt at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Merck had previously reported immunogenicity and safety data for its HPV vaccine (Gardasil) in younger males aged 9-15 years, but these are the first data on efficacy in males and the first findings in older adolescent and adult males.

The rationale for use of Gardasil in males is twofold. There is intrinsic benefit to males themselves since HPV strain 18 causes penile, anal, and oropharyngeal cancer and HPV 6 and 11 are associated with genital warts. There is also a public health benefit to vaccinating males against HPV since coverage among girls is likely to be incomplete, transition of HPV occurs efficiently between sexual partners, and “gender-neutral” vaccination would be expected to reduce overall viral transmission in the entire population, noted Dr. Haupt of Merck Research Laboratories, Whitehouse Station, N.J.

ACIP is expected to recommend the vaccine for use in males aged 11-12 at the adolescent visit, just as it is now given to girls. This should simplify implementation, Dr. Doug Campos-Outcalt of the University of Arizona, Phoenix, said in an interview.



Since, besides cervical cancer and those mentioned above, the Human Papilloma Virus is also implicated as the cause of half of lung cancers in non-smokers, many oral and throat cancers, and some prostate cancers, the universal vaccination of boys and girls will most likely save lives and prevent millions of people from disfiguring disease.

I've never seen a case of bacterial meningitis since I left med school, thanks to the vaccine against Hemophilis influenza or Hib. Perhaps the future doctors will never see cervical cancer and will be surprised when and if they see lung cancers.

Monday, March 30, 2009

Texas Legislators Seek to Limit Funds for Human Embryo Destruction

Senator Steve Ogden is a Texas Hero!

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

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

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

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


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

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

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

Sunday, March 29, 2009

Why the medical home sounds good but won't work

A sister Family Physician says in her blog, "Musings of a Dinosaur,"

It is the source of endless angst among family doctors in solo and small group practice, because the structure of the PCMH excludes us by definition. The PCMH is advertised to work best in large group practices like Kaiser and the Mayo Clinic. All I can say is "DUH!"You know what the PCMH really is? Nothing more than this:

IT'S A WAY TO MAKE LARGE GROUP PRACTICES WORK MORE LIKE A SOLO DOC!!!

I am already performing every meaningful function of the PCMH. So is virtually every physician in solo and small group practice. There is absolutely nothing to be gained -- and a significant amount of money to be lost; this thing is expensive! -- by adopting any of this PCMH shit. Somehow that doesn't seem to stop our Academy from tossing us to the wolves by simply ignoring us.

New England Journal of Medicine plays conscience politics ("Trust me, I will act against my conscience," cont'd)

The New England Journal of Medicine has published a "Commentary" by a lawyer who has worked for Planned Parenthood, concerning the practice of medicine and conscience.

I don't like to publish entire articles from subscription-only sources (especially one written by a lawyer), but this serious breach of ethics on the part of the NEJM should be documented.

The NEJM published this in advance of the dead-tree version because the last day for comments is the same day the paper Journal comes out.

This most definitely should have been in the "Free Content" form, and it is. We should thank the editors for this favor. Physicians and others who do not subscribe (to the tune of several hundred dollars a year) are able to read and answer this lawyer's viewpoint of the practice of medicine.

There is no opposing view offered. Yep, let's talk about "choice" and "consent." but only give their choice and their consent.

The essay contains more of the ridiculous examples that we should be used to by now: the author asks about a doctor who refuses to care for diabetics because his religion counts gluttony as a sin.

She calls abortion - all abortions, without making the distinction between elective abortion and those necessary to save the life of the mother - "standard of care."

More in a bit:


From the online version of the New England Journal of Medicine, published in advance of printing in the April 9, 2009 issue of the Journal:

The regulation, as explained in its text (see the Supplementary Appendix, available with the full text of this article at NEJM.org), aims to raise awareness of and ensure compliance with federal health care conscience protection statutes. Existing laws, which are tied to the receipt of federal funds, address moral or religious objections to sterilization and abortion. They protect physicians, other health care personnel, hospitals, and insurance plans from discrimination for failing to provide, offer training for, fund, participate in, or refer patients for abortions. Among other things, the laws ensure that these persons cannot be required to participate in sterilizations or abortions and that entities cannot be required to make facilities or personnel available for them. And they note that decisions on admissions and accreditation must be divorced from beliefs and behaviors related to abortion. On their face, these laws are quite broad.

But the Bush administration's rule is broader still. It restates existing laws and exploits ambiguities in them. For example, one statute says, "No individual shall be required to perform or assist in the performance of any part of a health service program or research activity funded" by DHHS if it "would be contrary to his religious beliefs or moral convictions."1 Here the rule sidesteps courts, which interpret statutory ambiguities and discern congressional intent, and offers sweeping definitions. It defines "individual" as physicians, other health care providers, hospitals, laboratories, and insurance companies, as well as "employees, volunteers, trainees, contractors, and other persons" who work for an entity that receives DHHS funds. It defines "assist in the performance" as "any activity with a reasonable connection" to a procedure or health service, including counseling and making "other arrangements" for the activity. Although the rule states that patients' ability to obtain health care services is unchanged, its expansive definitions suggest otherwise. Now everyone connected to health care may opt out of a wide range of activities, from discussions about birth control to referrals for vaccinations. As the rule explains, "an employee whose task it is to clean the instruments used in a particular procedure would also be considered to assist in the performance of the particular procedure" and would therefore be protected. Taken to its logical extreme, the rule could cause health care to grind to a halt.

It also raises other concerns. In terms of employment law, Title VII of the Civil Rights Act, which applies to organizations with 15 or more employees, requires balancing reasonable accommodations for employees who have religious, ethical, or moral objections to certain aspects of their jobs with undue hardship for employers. But the new rule suggests that if an employee objects, for example, to being a scrub nurse during operative treatment for an ectopic pregnancy, subsequently reassigning that employee to a different department may constitute unlawful discrimination — a characterization that may be at odds with Title VII jurisprudence.2 As officials of the Equal Employment Opportunity Commission remarked when it was proposed, the rule could "throw this entire body of law into question."3

Furthermore, although the rule purports to address intolerance toward "individual objections to abortion or other individual religious beliefs or moral convictions," it cites no evidence of such intolerance — nor would it directly address such intolerance if it existed. Constitutional concerns about the rule, including violations of state autonomy and rights to contraception, also lurk. And the stated goals of the rule — to foster a "more inclusive, tolerant environment" and promote DHHS's "mission of expanding patient access to necessary health services" — conflict with the reality of extensive objection rights. Protection for the silence of providers who object to care is at odds with the rule's call for "open communication" between patients and physicians. Moreover, there is no emergency exception for patient care. In states that require health care workers to provide rape victims with information about emergency contraception, the rule may allow them to refuse to do so.

Recently, the DHHS, now answering to President Barack Obama, took steps to rescind the rule (see the Supplementary Appendix). March 10 marked the beginning of a 30-day period for public comment on the need for the rule and its potential effects. Analysis of the comments (www.regulations.gov) and subsequent action could take some months. If remnants of the rule remain, litigation will follow. Lawsuits have already been filed in federal court, and Connecticut Attorney General Richard Blumenthal, who led one of the cases, has vowed to continue the fight until the regulation is "finally and safely stopped."4

This state of flux presents an opportunity to reconsider the scope of conscience in health care. When broadly defined, conscience is a poor touchstone; it can result in a rule that knows no bounds. Indeed, it seems that our problem is not insufficient tolerance, but too much. We have created a state of "conscience creep" in which all behavior becomes acceptable — like that of judges who, despite having promised to uphold all laws, recuse themselves from cases in which minors seek a judicial bypass for an abortion in states requiring parental consent.5

The debate is not really about moral or religious freedom writ large. If it were, then the medical profession would allow a broad range of beliefs to hinder patient care. Would we tolerate a surgeon who holds moral objections to transfusions and refuses to order them? An internist who refuses to discuss treatment for diabetes in overweight patients because of moral opposition to gluttony? If the overriding consideration were individual conscience, then these objections should be valid. They are not (although they might well be permitted under the new rule). We allow the current conscience-based exceptions because abortion remains controversial in the United States. As is often the case with laws touching on reproductive freedom, the debate is polarized and shrill. But there comes a point at which tolerance breaches the standard of care.

Medicine needs to embrace a brand of professionalism that demands less self-interest, not more. Conscientious objection makes sense with conscription, but it is worrisome when professionals who freely chose their field parse care and withhold information that patients need. As the gatekeepers to medicine, physicians and other health care providers have an obligation to choose specialties that are not moral minefields for them. Qualms about abortion, sterilization, and birth control? Do not practice women's health. Believe that the human body should be buried intact? Do not become a transplant surgeon. Morally opposed to pain medication because your religious beliefs demand suffering at the end of life? Do not train to be an intensivist. Conscience is a burden that belongs to the individual professional; patients should not have to shoulder it.

Patients need information, referrals, and treatment. They need all legal choices presented to them in a way that is true to the evidence, not the randomness of individual morality. They need predictability. Conscientious objections may vary from person to person, place to place, and procedure to procedure. Patients need assurance that the standard of care is unwavering. They need to know that the decision to consent to care is theirs and that they will not be presented with half-truths and shades of gray when life and health are in the balance.

Patients rely on health care professionals for their expertise; they should be able expect those professionals to be neutral arbiters of medical care. Although some scholars advocate discussing conflicting values before problems arise, realistically, the power dynamics between patients and providers are so skewed, and the time pressure often so great, that there is little opportunity to negotiate. And there is little recourse when care is obstructed — patients have no notice, no process, and no advocate to whom they can turn.

Health care providers already enjoy broad rights — perhaps too broad — to follow their guiding moral or religious tenets when it comes to sterilization and abortion. An expansion of those rights is unwarranted. Instead, patients deserve a law that limits objections and puts their interests first. Physicians should support an ethic that allows for all legal options, even those they would not choose. Federal laws may make room for the rights of conscience, but health care providers — and all those whose jobs affect patient care — should cast off the cloak of conscience when patients' needs demand it. Because the Bush administration's rule moves us in the opposite direction, it should be rescinded.

Dr. Cantor reports representing an affiliate of Planned Parenthood in a legal matter unrelated to conscientious objection. No other potential conflict of interest relevant to this article was reported.


Source Information

Dr. Cantor is an adjunct professor at the UCLA School of Law, Los Angeles.

This article (10.1056/NEJMp0902019) was published at NEJM.org on March 25, 2009. It will appear in the April 9 issue of the Journal.

References

1. 42 U.S.C.A. § 300a-7(d).
2. Shelton v. Univ. of Medicine & Dentistry of New Jersey, 223 F.3d 220 (3d Cir. 2000).
3. Pear R. Protests over a rule to protect health providers. New York Times. November 17, 2008:A14.
4. Press release of the State of Connecticut Attorney General's Office, Hartford, February 27, 2009. (Accessed March 20, 2009, at http://www.ct.gov/ag/cwp/view.asp?A=3673&Q=434882.)
5. Liptak A. On moral grounds, some judges are opting out of abortion cases. New York Times. September 4, 2005.

Thursday, March 26, 2009

Clues to how blood stem cells become activated (adult stem cells)

The National Institute of Health has a news release about research done with NIH funding. The researchers explored how hematopoietic or blood cell producing adult stem cells are activated. The NIH article is very detailed, but easy to read and understand. An adaptation of the press release is at Science Daily.

The research article was published in Nature Cell Biology. (The abstract is free, the article can be purchased by non subscribers, for $18. I think this will be one of the articles that will eventually be published for free, since the research was Federally funded.)

From the NIH Press release:


For Immediate Release
Wednesday, March 25, 2009

E-mail this page
Subscribe Contact:
Robert Bock or Marianne Glass Miller
301-496-5133

Researchers Decipher Blood Stem Cell Attachment, Communication
Finding Has Implications for Leukemia Treatment, Artificially Culturing Blood Cells

Researchers at the National Institutes of Health have deciphered a key sequence of events governing whether the stem cells that produce red and white blood cells remain anchored to the bone marrow, or migrate into the circulatory system.

An understanding of the factors that govern migration of blood stem cells might lead to improved treatment of leukemia, a cancer that affects circulating white blood cells. The findings also have implications for culturing infection-fighting immune cells outside the body, where they could be temporarily held in storage during chemotherapy and other treatments which suppress the immune system. Moreover, the findings could contribute to a strategy for growing large quantities of red blood cells in laboratory dishes outside the body, to reduce the need for blood donations.

Previously, researchers thought that the cellular environment in which the stem cells reside produced the chemical signals that determined whether the cells would be stationary or free–floating. The current study provides evidence that the stem cells produce chemical signals of their own that may, in turn, influence the chemical signals they receive from their environment.

"This important discovery will advance our understanding of how blood cells and immune cells are generated," said Duane Alexander, M.D., director of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The findings were published on line in Nature Cell Biology. The study was conducted in the laboratory of Jennifer Lippincott-Schwartz, Chief of the NICHD Section on Organelle Biology. The study’s first author was Jennifer Gillette, also of the Section on Organelle Biology. Other authors were Andre Larochelle and Cynthia E. Dunbar of the Hematology Branch of NIH's National Heart, Lung, and Blood Institute.

Dr. Gillette explained that hematopoetic progenitor stem cells — the cells which give rise to red blood cells and immune cells — travel between the bloodstream and the bone marrow. Within the bone marrow, they anchor themselves in place by attaching to bone marrow cells called osteoblasts.

Other studies have shown that osteoblasts secrete a substance that acts as a chemical signal that regulates the attachment of the stem cells. Large amounts of the chemical, which is known as SDF-1 (stromal cell derived factor-1), cause the stem cells to leave the bone marrow and enter the bloodstream. A small, continuous pulse of SDF-1, however, attracts the stem cells and results in their attachment to the osteoblasts.

In laboratory cultures, Dr. Gillette and her coworkers incubated unattached stem cells with osteoblasts. As the stem cells approached the osteoblasts, they developed long, tentacle-like projections, called uropods. The uropods attached to the surface of the osteoblasts. Then, a small portion of a uropod was absorbed inside an osteoblast. The uropod material was eventually sealed inside an endosome — a tiny balloon–like structure within the cell. After the osteoblasts absorbed the uropod material, they began producing SDF-1.

Dr. Gillette noted it appeared to be the stem cell material that stimulated the osteoblast to produce SDF-1, the substance that causes the stem cell to remain attached to the osteoblast or migrate into the blood.

"Our study indicates that stem cells may actually be able to manipulate the signals that they receive from their environment," Dr. Gillette said. "Stem cells seem to have a little more control than we thought."

Monday, March 16, 2009

The "Rescission of the Regulation Entitled 'Ensuring That Department of Health and Human Services Funds Do Not Support Coercive or Discriminatory Policies or Practices in Violation of Federal Law'” was posted on the Federal Register on March 10th, with the announcement of a 30 day period in which to comment. The full announcement can be read here. (PDF Acrobat document) Comments must be made by April 9th.

Please consider taking a look at the website Freedom2Care to learn more about the problem of restricting conscience. You can use one of their forms online to let the Administration and Health and Human Services Secretary Sebelius know how you feel or to tell your story.

To send a comment directly to the HHS, go to the website, http://www.Regulations.gov and fill in the form there or send an email to proposedrescission@hhs.gov.

Saturday, March 07, 2009

Obama will fund more losing embryonic stem cell research (New Yellow Brick Award to the President)

Just days after we hear about functioning induced Pluripotent stem cells from adult skin cells, cells that can produce dopamine, the proteins missing in Parkinson's disease, we read that President Obama is going to overturn the limits on funding for embryonic stem cell research. Despite the fact that these cells match the patient because they come from the patient, that they will be cheaper, more accessible and we believe have less risk of causing cancer, this Monday morning, the 9th of March, 2009, the White House plans a quiet ceremony to sign the Executive Order.

Follow the Yellow Brick Road, Mr. President. The great embryonic Oz will get you home. Do not look behind the curtain, ignore that little man.

"Stroke of the pen, law of the land. Kinda cool!" (Thank you, Paul Begala.) We've been trying to spend a Trillion dollars every 10 days in the Obama administration. Let's just throw more good money after bad.

Typical of the news articles, is this one, from the US News and World Report, entitled (sigh)"Obama to End Stem Cell Ban Monday
Researchers applaud his action, which is expected to kick-start efforts to unlock therapeutic potential."

I recommend that you read that link above, in order to compare reality with what the proponents of destructive embryonic stem cell research believe.

The article is so full of holes. The title and first paragraph say "ban." There never was a ban. Ask Daley and Melton of Harvard who have been creating embryos for destruction to harvest the parts.

And then, there's this gem of an emotional non sequitor, I'm afraid from my State of Texas:

"It's going to remove an embarrassment for American science," said Dr. Darwin Prockop, director of the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White Hospital in Temple, said in February. "It's a statement that we're going to again believe in science."

Prockup must have been teased too much about his name as a child. Seriously, who among us stopped and now started to believe in science again?

We are not behind, we are not embarrassed, unless it's in imposing regulations. Even the "Progressives" are calling for more restrictions. The UK has more regulations on regenerative medicine and embryonic research than the US. France, Germany and Israel have similar limits on funding. Germany, at one time had criminal charges and fines attached to their ban.

CIRM has $3 Billion which must be spent on cloning and embryonic stem cell research. Their "Strategic Plan?" (This is a pdf, for a review, read this article at the CIRM website.) One cure and 2 trials in ten years. Who thinks the US is going to top their billions in embryonic research, when results with induced Stem Cells are bounding ahead?

Oh, I know, CIRM thinks the NIH should buy their $400 Million in bonds, this year. No one else wants the losing proposition.

Friday, March 06, 2009

Non-embryonic stem cells to cure Parkinson's?

The journal, Cell, has published an article (free abstract, full article and supplements for purchase) on patient-derived induced Pleuripotent Stem Cells (iPSC's) that appear to be brain neurons that produce dopamine, which is lacking in Parkinson's patients.

Besides being derived from the patient's own skin cells (they won't be rejected and are cheaper and more accessible to more of us than embryonic), and being non-destructive (no embryos destroyed - and, did I say, cheaper and more accessible?), these iPSC's were derived using viruses that can be purposefully, and apparently, fully removed from the culture.

The plans apparently are to use the cells to study the disease. However, with the history of the debate over this disease, I wouldn't be surprised to see them used to treat the donors' Parkinson's disease very soon. Parkinson's is so devastating to patients and their families that several attempts to use brain transplants of aborted embryonic and fetal tissues have been used on real patients, with disastrous results. These iPSC's should be safer than fetal tissues.

Trust me, I have no conscience (Again and again, and again)

Siricou Raven, that gadfly of the prolife blogger, says I'm using scare tactics, that the NHS pays for dialysis, and that we pro-conscience doctors are afraid that 'THE GAYS WILL DESTROY MEDICINE!!!!' Oh, and Bush did it!

Well, what do you expect of people who don't have consciences and who are told by the Powers that be that we must violate any oaths we've taken for money and law?

It's not Gays and Lesbians we're trying to protect ourselves and our consciences from - its their lawyers. Beginning in 2005 and through last month, ACOG broke one of the strongest tenets of modern medicine: Thou shalt not put thy colleagues in greater malpractice risk.

The conscience protection ruling is a synthesis of current laws. The synthesis was only necessary because in 2005, the American College of Obstetricians and the American Board of OBGyn turned their quiet attack on pro-life residency candidates (few programs will accept pro-life doctors) into an effort to change laws (lobbying the US Senate) and amended their own ethics policies to put not only ACOG members, but all doctors at risk of losing their certification, their licenses, and increased our lawsuit risk.

Obama, what's-her-name, and Daschle are bought and paid for by Planned Parenthood and NARAL. (Daschle sent out letters against George Bush in '04, on NARAL's letter head. After the SCOTUS allowed the Partial Birth Abortion Ban, Sebelius vetoed 3 separate bills due to their limits on abortion. And Obama made his famous "first thing I do is sign FOCA" speech to PP)

Most people have access to the $4 Walmart drugs. Our little town has 2 low cost clinics, one is free of charge, one has a cost of less than $5. Everyone who can raise the money can have the latest and greatest -- not so in the NHS. A few years ago, it was illegal to sell Tamiflu in Great Britain, because NICE said it was.

Years before that, Dialysis was limited to those under 55 years old. Echoing that, this year, a man in his 50's was told he would not get surgery to stabilize his ankle until he kicked his nicotine habit.
http://www.dailymail.co.uk/news/article-481617/Doctors-refuse-fix-builders-broken-ankle-unless-quits-smoking.html

Our hospital has indigent care, as does our County. We doctors see patients for cash and are aware when their costs are out of pocket. (My phone has a program that has formularies for local insurance plans. The patient and I discuss whether they want the once a day Tier 4 drug, the twice a day Tier 3 or the 4 times a day generic.)

Wednesday, March 04, 2009

This is your future on Government Medicine

Imagine that it is 2016, and you are a 65 year old boomer. You have been admitted to your local community hospital with malaise, fatigue, vomiting and cloudy mental status. You have had blood pressure problems and diabetes for a few years, and have just been diagnosed with renal failure. As you drift in and out of consciousness, you are vaguely aware your old family practice physician, who had taken care of you for 20 years, is not around. A religious man, he quietly retired from medical practice in 2014, after the full force of the Obama administration‘s removal of conscience protection for physicians in February, 2009, came into effect.
Read the whole article for a chilling look at the future and a concise review of how we got to this point.

Bravo, Dr. Davenport!

Tuesday, March 03, 2009

Goodbye Medicare, hello County Clinic

Where is the outrage over the destruction of (what is left of) Medicare and the debt we owe to veterans? I'm afraid that we're not talking about "Medicare for all," or even "Medicaid for all." We're talking about County Clinic for all.

For a look at the proposed cuts in cost for Medicare, take a look a this table.

Consider that "reduce costs for re-admissions" and the "bundling" of hospital and outpatient costs after a hospitalization.

That means that Medicare will only pay a flat fee to the hospital for any hospitalization and follow up care after the hospitalization and will not pay if the patient has to be readmitted for complications or a new illness within a certain period of time. Patients would not be able to return to their family doctor for follow up care, unless the doctor works for the hospital. And there would be a lot of pressure to keep patients out of the hospital.

People who "cost" Medicare the most money would be encouraged to forgo care. I predict a huge push for hospice care for anyone with complicated, chronic diseases. (Or, possibly, a back-alley, underground medical care system for cash and barter. Wonder how long that will be legal?)

The AMANews reports that coordination of care doesn't lower costs to Medicare, only 2 out of 15 of the model centers cut patients' days in the hospital, and that the coordination is burdensome for small and solo practices. For every 100 patients, we interact with 99 other doctors in other practices. (I knew it was a lot.) (I don't think any of these links require subscription, let me know if there's a problem.)

This is my favorite part from that article:

"It doesn't matter if you back up a truck to their offices and drop off bundles of money," Dr. Norman said. "They don't have the time, resources or expertise right now to put this all in place."


Speaking of "bundles of money," the stimulus has a chunk to support Community Health Centers, as reported by Reuters' Maggie Fox. Will these centers really be open longer hours, as advertised, and will they continue to mandate the hiring of mid-levels (Nurse Practitioners or Physician Assistants), rather than allowing the hiring of physicians with the grants, as currently the case for other Federally funded clinics?

The budget includes plans to pay for the 667 Billion dollar health care for all by cutting payments to “providers” (including doctors and hospitals, pharmacists and wheel chair companies), according to the Wall Street Journal. We're already scheduled to have that automatic “Sustainable Growth Rate” 20% cut in Medicare payments to doctors, next year. Want to bet that the cut won't go through and/or won't be considered part of the "savings"? (And mesh with the President’s plans to cut the deficit.)

That WSJ and the LATimes articles also mention a “public” health care plan, and possible new taxes (on the employer’s portion of insurance payments or a new income tax).

Speaking of which, the Massachusetts mandatory health insurance trial isn’t working - even to make sure that people have insurance or are able to see their doctor in a timely manner - according to the Boston Globe The solution? That old United States National Health Insurance Act, paid for by "a modest progressive tax."

Monday, March 02, 2009

AMA: "People aren't going to waste time on Embryonic Stem Cells, anymore"

A member of the "lobby group Comment on Reproductive Ethics" maintains that there are "some scientists who like to hold on to what they've got, but" she doesn't "think people are going to waste time on embryonic stem cells any more."
(Josephine Quintanelle, quoted in the Guardian, 3/1/09)

The American Medical Association sends its members a "Morning Rounds" email with the latest headlines on science and medicine. The articles have more links than my posts and the editors seem to choose that days' big story.

Today's big story is that the Washington Post (free registration required) reports on a from a Letter to the journal, Nature. Two groups of scientists, one from Toronto (Andras Nagy, from the University of Toronto) and another from Edinburgh (Dr Keisuke Kaji, at the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh) have found a way to make skin cells transform into embryonic-like stem cells without using viruses.

This should lead to a cheaper way for people to have their own cells transformed into therapies. Farther down the line, it could help us treat disease and injury -and aging - in place, by inducing repair where it's needed and without transplants. On the other hand, if we use embryonic stem cells, it would be necessary to make a clone of each person or find some sort of universal donor cell that would not be rejected. The previous way of reprogramming cells to an embryonic stage used viruses that could not be removed and which have the potential to cause cancer if left in the DNA of the cells.

The scientists used human fibroblasts - a type of skin cell - which were treated with a "jumping gene" from a cabbage looper moth, that inserts itself into chromosomes along with the genes that "reprogram" the fibroblast -- then, the extra gene can be removed.

From the Post, a very clear description.

The alternative cells, known as induced pluripotent stem cells, or iPS cells, appear to have many of the same characteristics as embryonic stem cells but are produced by activating genes in adult cells to "reprogram" them into a more primitive state, bypassing the moral, political and ethical issues surrounding embryonic cells. Until now, however, their use has been limited because the genetic manipulation required the use of viruses, raising concerns the cells could cause cancer if placed in a patient. That has triggered a race to develop alternative approaches.

"These viral insertions are quite dangerous," Nagy said.

In the new work, Nagy and his colleagues in Toronto and at the University of Edinburgh in Scotland instead used a sequence of DNA known as a transposon, which can insert itself into the genetic machinery of a cell. In this case, the researchers used a transposon called "piggyBac" to carry four genes that can transform mouse and human embryonic skin cells into iPS cells. After the conversion took place, the moth gene, called "piggybac" lost its ability to insert itself into the chromosomes of the cells and "disappear" or can be removed.

"PiggyBac carries the four genes into the cells and reprograms the cells into stem cells. After they have reprogrammed the cells, they are no longer required, and in fact they are dangerous," Nagy said. "After they do their job they can be removed seamlessly, with no trace left behind. The ability for seamless removal opens up a huge possibility."


Unfortunately, for some reason the scientists used (non-stem) fibroblast cells from embyros as the cells that are reprogrammed, so the research is being repeated in cells from non-embryonic sources.

Other news articles on the breakthrough are at BBC News, Nature News,
AFP, Financial Times, the Candian Press, the Guardian and the Globe and Mail.

Friday, February 27, 2009

Obama moves to overturn Conscience rules

For a couple of years, LifeEthics has covered the conscience of physicians and what it would mean if a doctor, nurse or hospital were to be forced to go against their consciences. My review is here.

From the LA Times, we learn that President Obama plans to rescind the ruling clarifying conscience laws in force in the US today:

Conscience' rule on abortions may be overturned
The Obama administration wants to clarify a Bush policy that lets healthcare workers deny services because of moral beliefs.
By Noam N. Levey
February 27, 2009
Reporting from Washington -- Taking another step into the abortion debate, the Obama administration today will move to rescind a controversial rule that allows healthcare workers to deny abortion counseling or other family planning services if doing so would violate their moral beliefs, according to administration officials.

The rollback of the so-called conscience rule comes just two months after the Bush administration announced it late last year in one of its final policy initiatives.


Inevitably, no matter what they say, the outcome will be to further politicize abortion and to force doctors to perform abortions and assisted suicide, force Catholic hospitals to allow abortions and sterilizations and - inevitably - physician assisted suicide.
Last month without official ceremony, Obama overturned a controversial ban on U.S. funding for international aid groups that provide abortion services.

The move by the Department of Health and Human Services to throw out the conscience rule is being made equally quietly as most of Washington focuses on the president's blockbuster budget plan.

On Thursday officials stressed that before the administration finalizes the rollback, a standard 30-day comment period seeks input from people across the ideological spectrum.

"We believe that this is a complex issue that requires a thoughtful process where all voices can be heard," said one official, who was not authorized to speak on the record about the policy change.

The officials said the administration would consider drafting a new rule to clarify what healthcare workers could reasonably refuse to do for their patients.

For more than 30 years, federal law has allowed doctors and nurses to decline to provide abortion services as a matter of conscience, a protection that is not subject to rule making.

In promulgating the rule last year, then-Health and Human Services Secretary Mike Leavitt said it was necessary to address discrimination in the medical field.

Thursday, February 26, 2009

Whose life is it, anyway?


Trait selection in babies "is a service," says Dr. Steinberg. "We intend to offer it soon."


Whoops, someone noticed that some of this reproductive technology stuff might not be ethical.

Talk about controlling parents!

Eugenics is a done deal. The cat's out of the bag. There's no going back. (Don't think about the 14th Amendment that overturned Dred Scot and took the slaves from their "owners.")


Of course, the "Progressives" and human-plus groups only commit *good* eugenics. All they want is control and more money.


The "Progressives" started raising the alarm a couple of years ago, when they were pushing for a change in the Bush embryonic stem cell policy. The logic was that the reason there is no regulation is that the government isn't paying for enough research.

At the same meetings, they were adamant that their group must have the power maintain control. (Alta Charo, Laurie Zoloth, Jonathan Moreno, Insoo Hyun and the rest of the "Ethicists for Hire" crowd.)

Funny, in all these links, I didn't find a single comment about the doctors who lost a discrimination suit in California for refusing to fulfill a patient's request for IVF -- even in the midst of the hulabaloo about the mother of octuplets.

HT to Vox Popoli

Saturday, February 21, 2009

US behind on regulation of reproductive technology

After hearing/reading for the last 8 years that there is too much regulation of research, there's now a call from the Jonathan Moreno and the "Progressives"(at the website that grew out the Center for American Progress, originally founded by John Podesta, Obama's advisor) for regulation of reproductive technology. See this post at the "Science Progress" blog.

Scroll down to the middle of the blog post on regulation to see a fantastic interactive map of regulation across the world.

Unfortunately, the regulation may not be easy to come by, or what those of us who are pro-life might wish for. The progressives mock those of us who believe that even embryonic humans have the right not to be intentionally killed or enslaved. See the comments in this review of Yuval Levine's book, Imagining the Future.

Wednesday, February 04, 2009

Human cloned embryos

Oddly, there is very little notice of the confirmation that Advance Cell Technology has created cloned human embryos. Current bioethics and science reporting evidently takes the creation and destruction of human embryos for granted. In fact, the embryonic humans were created with the intention of destroying them.

No one - or almost no one - seems to notice.


Wired Science
has one of the few reports that narrows in on what should be the headline:"Research Breakthrough: Human Clones May Be Genetically Viable."

It is significant that (as reported earlier) human-animal hybrid embryos do not appear to be a practical source for human embryonic stem cells. However, after reading the article itself, it appears that the story with in the story may be - I believe should be - even more significant.

The article, "Reprogramming of Human Somatic Cells Using Human and Animal Oocytes," is available online and free, here, in pdf form. Supplemental information is available here.

Lanza and his colleagues report that they used human eggs and human donor DNA to create about 50 cloned human embryos, all females. They also write that they used a human embryo started by in vitro fertilization as a "control," or material to test the validity of their other results.

Cells were removed for testing from some of the cloned human embryos and the IVF human embryo. Other than that, we do not know the fate of these embryonic human girls.

Edited January 27, 2010 to correct a "Label" typo

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

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

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

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

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

See my Update, written after I read the report.