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Writer's pictureKirk Hartley

Scientists and a Kinky-Tailed Mouse Highlight Reasons to Applaud the Removal of the Injunction Limit

My 54th birthday brought an unexpected present. On April 29, 2011, the DC Circuit vacated the nation-wide injunction limiting stem cell research involving federal funding, as is well-described by Lyle Denniston at Scotusblog. The opinion is here. Thank goodness for appellate courts, the Obama Administration pressing the appeal quickly, and true scientists supportiing the effort to overturn the injunction.

It’s hard to grasp why the injunction was ever issued given the public interest factor for issuing injunctions. Delaying research is not simply an abstract issue. To say the least, stem cell research goes to the heart of diseases (e.g. cancers) which kill thousands every day, and to profound injuries that can devastate lives. Stem cell research also is big business, and would be bigger here except that the restrictive limits push researchers outside the US.

As it happens, ScienceDaily this week brought news of new research papers which highlight the importance of basic and wide-ranging research to fully understand stem cells and their internal cellular components. Thus, this April 26, 2011 ScienceDaily article highlights an April 15, 2011 online paper reporting that scientists researching breast cancer recently found evidence that some breast cancer cells can go backwards to become a stem-cell like cancer cells:

ScienceDaily (Apr. 26, 2011) — Whitehead Institute researchers have discovered that a differentiated cell type found in breast tissue can spontaneously convert to a stem-cell-like state, the first time such behavior has been observed in mammalian cells. These results refute scientific dogma, which states that differentiation is a one-way path; once cells specialize, they cannot return to the flexible stem-cell state on their own.

This surprising finding, published online in the Proceedings of the National Academy of Sciences (PNAS), may have implications for the development of cancer therapeutics, particularly those aimed at eradicating cancer stem cells.

"It may be that if one eliminates the cancer stem cells within a tumor through some targeted agent, some of the surviving non-stem tumor cells will generate new cancer stem cells through spontaneous de-differentiation," says Whitehead Founding Member Robert Weinberg. Cancer stem cells are uniquely capable of reseeding tumors at both primary and distant sites in the body.

As to the value of fundamental research, ScienceDaily noted here that one of the world’s great medical journals – Cell – includes a new paper highlighting a fundamental new discovery on the path of genetic mutations. The new paper is set out as the featured and free article of Cell’s April 29, 2011 issue, and is accompanied by a video and graphic explanations. The new knowledge arises from research lead by University of San Francisco scientists who unraveled a genetic mystery embodied in a mutant mouse first noted by NIH researchers back in the 1940s. The mutant mouse was notable for a short, kinky tail and a neck with an extra set of ribs. Back in the 1940s, the scientists lacked the tools needed to understand the mutation, but they kept breeding the mouse line, knowing the future should bring new analytic tools.

As reported in Cell, the research team used today’s new tools and the line of mutant mice to learn that a cell component known as the ribosome has a heretofore unknown role in determining which proteins are produced by our cells, and how one missing protein could produce the mutations. The conclusions almost certainly apply to humans because cells are cells. This is major science news because – until now – the ribosome was known as simply a production machine that did not influence outcome. To learn that the ribosome may alter outcome is fundamental and highly important new knowledge, as illustrated by Cell giving the paper so much coverage. (Sad to day, it’s far too easy to think of various newly-elected US Representatives, and envision an uninformed, budget-cutting tea-partier deriding the research as "wasting money for over 60 years on trying to find out why some mice have kinky tails". )

Most scientists "get" the importance of stem cells and wide-ranging research on their characteristics. Indeed, only a zealous few argue that their personal, "moral" beliefs are more important than scientific knowledge. Thus, national scientific research leaders actively opposed the injunction, and submitted evidence opposing the injunction, as described in this press release from the University of California at San Francisco. The comments illustrate the point that research delays and injunctions are not abstract matters:

____________________________________________________

April 29, 2011

The U.S. Federal Court of Appeals has overturned an August 2010 ban on federal funding of embryonic stem cell research, paving the way for broader exploration of how stem cells function and how they can be harnessed to treat a wide range of currently incurable diseases

The ruling has been welcomed by the Obama Administration, which attempted to lift the ban in 2009, and by the nation’s top researchers in the field, including Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

“This is a victory not only for the scientists, but for the patients who are waiting for treatments and cures for terrible diseases,” Kriegstein said. “This ruling allows critical research to move forward, enabling scientists to compare human embryonic stem cells to other forms of stem cells, such as the cell lines which are derived from skin cells, and to pursue potentially life-saving therapies based on that research.”

Kriegstein said the ruling will make a significant difference for stem cell research in general, including at UCSF, where the majority of stem cell investigators receive some funding from the National Institutes of Health for their research, as well as from private sources and from the state. The ruling enables those scientists to integrate research from various funding sources, thereby more quickly addressing the causes and therapies for diseases.

Kriegstein was one of two University of California scientists to file a Declaration in September 2010 in support of the UC Board of Regents’ motion to intervene in the August lawsuit, Sherley v. Sebelius.

Sherly v. Sebelius had argued that when the Obama Administration lifted a ban on federal funding for the research in March 2009, it had violated the 1996 Dickey-Wicker Amendment which barred using taxpayer funds in research that destroyed embryos.

In response, a U.S. District Court judge temporarily ordered a ban on the use of federal money for the research until the court battle could be resolved.

The Appeals Court decision put the Dickey-Wicker question to rest, ruling that the amendment was “ambiguous” and that the NIH “seems reasonably to have concluded that although Dickey-Wicker bars funding for the destructive act of deriving an ESC (embryonic stem cell) from an embryo, it does not prohibit funding a research project in which an ESC will be used,” according to the 2-1 decision.

“I am very happy with this decision, although I am surprised that it wasn’t a unanimous vote,” Kriegstein said. “In my opinion, the evidence in favor of pursuing this research is overwhelming compared to the arguments submitted to stop the research.”

UCSF is one of two universities, along with the University of Wisconsin, that pioneered human embryonic stem cell research in the United States, beginning in the late 1990s.

UCSF has developed one of the largest programs in the nation, primarily funded by the California Institute for Regenerative Medicine, a voter-supported initiative that provided $3 billion to fund statewide research in lieu of federal funding for it. Funding from the NIH, private philanthropy and other state sources also have been critical for the program.

UCSF also launched the nation’s first stem cell PhD program in 2010, for which the first class already has been chosen and will begin in fall 2011.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For more information, visit www.ucsf.edu.

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