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.

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.

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."

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.