Imagine a bizzaro universe in which Bush administration officials have to explain why they were so intent on paying for human embryonic stem cell research that they violated federal law to do it. In that same alternate reality, a court rules that none of the embryonic cell lines used by medical scientists for 10 years could continue to be applied to important research.

If your credulity hasn’t already been strained to the breaking point, now imagine that you’re a scientist who went to his or her lab this morning not knowing if you could continue your work on, say, Alzheimer’s disease, Parkinson’s or diabetes, work that was funded by the National Institutes of Health months ago that you were doing just yesterday. These are all plausible inferences that could be drawn from a United States District Court judge’s August 23 decision.

Welcome to the real world. Judge Royce Lamberth issued a preliminary injunction that stops funding for human embryonic stem cell research because, he said, the plaintiffs are likely to succeed when their complaint has a full hearing and they would be irreparably harmed if the funding were to continue in the meantime. Why did the judge reason that this attempt to stop the research would likely succeed? Mainly because he agrees that the federal funding violates the 1995 Dickey-Wicker amendment to the National Institutes of Health budget, which prohibits the federal government from paying for research that destroys human embryos.

Yet the Clinton, Bush, and Obama administrations all agreed that federal funds can be used to support research on cells that are laboratory-grown descendents of human embryo cells since that research is on cultured cells, not on embryos, and because the federal funds were not used to conduct research on, much less harm, any embryos themselves. No one during the Bush administration, which was not terribly friendly to embryonic stem cell research, objected to this interpretation of the law.

The Department of Justice has yet to interpret fully the judge’s decision, but one reading of the injunction is that the clock on federal stem cell policy is turned back to 2000. Even research on stem cell lines still in use that were approved for research by the Bush administration would have to stop.

Moreover, Judge Lamberth’s decision reveals a stunning disregard for the precedents he is compelled to follow. Under the Supreme Court’s landmark decision in Chevron v. NRDC, a judge must apply a high degree of deference to an agency’s reading of a statute unless the statute’s words are completely unambiguous. So, in refusing to defer to three administrations’ interpretation of the law, Judge Lamberth effectively concluded that all three of them don’t know how to read.

Simply put, it’s far more likely that a single trial judge misread the law than it is that three ideologically diverse administrations all made the same blatant mistake.

Even the application of the Dickey-Wicker amendment to embryonic stem cell research that the court relies on is forced. When Congress passed Dickey-Wicker in 1995 it could not have been thinking about human embryonic stem cell research, which didn’t start until a breakthrough at the University of Wisconsin in 1998. Rather, the amendment was created out of concern for using whole embryos in research, perhaps even creating them for that purpose. Congress wasn’t thinking one way or another about work on cell lines descended from embryos long ago. But now the judge is telling us that the law applies to a condition that could not have been part of congressional intent and is logically distinct from its object.

And the very legal standing that allowed the complainants to get into the court in the first place makes little sense. The plaintiffs include scientists who do research on adult stem cells. They claim they are harmed by the current funding policy because of unfair competition with embryonic stem cell research. But there is no cap on stem cell funding. The NIH will give grants based on the quality of the proposed work, not on the materials to be used.

In fact, adult stem cell research has received three times as much funding as embryonic. Over the past decade funding for adult stem cells has increased, not declined, and it has done so partly because of the greater understanding of stem cell biology gained from work with embryonic stem cells. Where’s the harm to the scientists who work on the adult cells? If their argument prevails they will have used to the courts to elbow out their scientific competition!

The scientists who in good faith have been working on NIH funding for the embryonic stem cell work are the ones who could suffer irreparable harm. More important, so could the rest of us. What the opposition to this legitimate and globalized field has been unable to do through science and the ballot box they are trying to do through the courts. Let us hope they have only been able to delude a single poorly informed judge.

Update 8-25-10: NIH director Francis Collins has announced that, in light of the court’s preliminary injunction, 50 new grant applications will be withdrawn from scheduled peer review and 12 grants worth an estimated $15 million to $20 million that have already gone through initial review will be stopped. Another 22 grants totaling $54 million that already are under way and scheduled for annual review in September will be stopped.

As Dr. Collins told reporters: “This will mean very promising research will not get done, screening for new drugs will stop, and researchers who have been energized will likely grow discouraged and move to other countries or on to other research.”

So much for the plaintiffs’ contribution to American science.

Jonathan D. Moreno, Ph.D., is the David and Lyn Silfen University Professor of Ethics and Professor of Medical Ethics and of the History and Sociology of Science at the University of Pennsylvania, and the Editor-in-Chief of Science Progress.

In our shrill political climate let’s celebrate the quiet passing of a science milestone.

Last week the Food and Drug Administration gave its first approval for a clinical trial of an embryonic stem cell treatment. Embryonic stem cells are special because they can grow, or differentiate, into any kind of human tissue. Many believe they hold great promise for treating a wide range of diseases and disorders, from Alzheimer’s to cancer to spinal cord injuries to blindness.

The FDA had put the application from biopharmaceuticals company Geron Corp, which produced the cells, on clinical hold after some mice given the treatment developed tiny spinal cysts. But another animal study found no cysts. The testing will involve patients with recent spinal cord injuries, who will receive infusions of embryonic stem cells that have been differentiated into cells that can produce myelin, the coating that conducts electrical impulses in the spine.

There is no expectation that this cell treatment would magically regenerate spinal cords, though much could be learned from a greater understanding of how new cells integrate into damaged tissue. Rather, the goal is to facilitate some improved potential for movement along with strenuous physical rehabilitation. It is thought that recently injured patients might be more susceptible to improvement.

The company is reported to have spent $150 million to get the trial approved.

The stem cells developed by the company are derived from an embryo that was left over following fertility treatment. It had to be donated with full informed consent by the couple. Geron was able to proceed with the lab work to develop the treatment in spite of the Bush administration policy that severely limited federally funded embryonic stem cell research. Several years ago the company produced dramatic footage of injured rats that had been treated with the cells and were able to regain movement.

The greatest concern that experts have about the trial is that potent cells injected into the spine might develop into tumors called teratomas. This worry explains the FDA’s cautious approach. Although there are nonembryonic stem cell treatments for spinal cord injury that have been tried, they have been criticized for inadequate safety data from animals and unclear explanations of surgical procedures. By contrast, owing to the potential harm, novelty, and public controversy, the Geron trial is surely among the most intensively reviewed proposed clinical trials in history.

All this does not guarantee success, of course, nor does it guarantee that no harms will result. This is biology in the real world, not a computer simulation. But it does establish a reasonable regulatory pathway for human embryonic stem cell treatments for serious diseases that currently have only very inadequate therapies, a milestone that would have been all but political science fiction just a few years ago.

Meanwhile, thanks to the Obama administration’s responsible stem cell policies, dozens of new embryonic stem cell lines are being approved for federally funded research under grants from the National Institutes of Health. This should lead to more academic centers engaging in targeted research with these and other stem cells sources.

While the FDA’s approval of the Geron trial is just a small incremental step forward for potentially lifesaving research, it represents a significant break from past bickering, and raises the inkling of hope that someday we may wonder what all the shouting was about.

Jonathan D. Moreno, Ph.D., is the David and Lyn Silfen University Professor of Ethics and Professor of Medical Ethics and of the History and Sociology of Science at the University of Pennsylvania, and the Editor-in-Chief of Science Progress.

That’s appropriate, since Detroit is suffering through economic hard times and stem cell research provides good jobs, and will lead to even more good jobs when it leaves the laboratory and becomes the source of new medical technologies. This annual meeting brings together the diverse community of people worldwide who support the research, ranging from the scientists themselves to industry leaders, funders and philanthropists, patient advocates, and educators. Their shared aim: to review the current state of the research and chart the future of regenerative medicine. As well, the summit fosters international collaboration that can really move this life-saving effort forward. You can find out more at: www.worldstemcellsummit.com

“We are delighted to bring the 2010 World Stem Cell Summit to Detroit,” said Bernard Siegel, executive director of the Genetics Policy Institute. “Michigan is fast becoming a biotechnology hub. Michigan State University, the University of Michigan and Wayne State University all have world-class researchers and outstanding facilities dedicated not only to fundamental stem cell research but also to translating lab work into effective treatments and cures.”

I remember Bernie from our "First International Stem Cell Action Conference" held in Berkeley back in ‘04. He has contributed so much to our cause over the years. Check out his organization: Genetics Policy Institute.

Better understanding of mechanisms involved should improve reprogramming of embryonic-like cells.

Scientists may be one step closer to being able to generate any type of cells and tissues from a patient’s own cells. In a study that will appear in the journal Nature and is receiving early online release, investigators from the Massachusetts General Hospital Center for Regenerative Medicine (MGH-CRM) and the Harvard Stem Cell Institute (HSCI), describe finding that an important cluster of genes is inactivated in induced pluripotent stem cells (iPSCs) that do not have the full development potential of embryonic stem cells. Generated from adult cells, iPSCs have many characteristics of embryonic stem cells but also have had significant limitations.

"We found that a segment of chromosome 12 containing genes important for fetal development was abnormally shut off in most iPSCs," says Konrad Hochedlinger, PhD, of the MGH-CRM and HSCI, who led the study. "These findings indicate we need to keep improving the way we produce iPSCs and suggest the need for new reprogramming strategies."

Although iPSCs appear quite similar to embryonic stem cells and give rise to many different types of cells, they have important limitations. Several molecular differences have been observed, particularly in the epigenetic processes that control which genes are expressed, and procedures that are able to generate live animals from the embryonic stem cells of mice are much less successful with iPSCs.

Previous studies have compared iPSCs generated with the help of viruses, which can alter cellular DNA, to embryonic stem cells from unrelated animals. To reduce the chance that the different sources of the cells were responsible for observed molecular differences, the MGH/HSCI research team prepared two genetically matched cell lines. After generating mice from embryonic stem cells, they used a technique that does not use viruses to prepare lines of iPSCs from several types of cells taken from those animals. They then compared the iPSCs with the original, genetically identical embryonic stem cells.

The most stringent assay of cells’ developmental potential showed that two tested lines of embryonic stem cells were able to generate live mice as successfully as in previous studies, but no animals could be generated from genetically matched iPSCs. Closely comparing RNA transcription profiles of several matched cell lines revealed significantly reduced transcription of two genes in the iPSCs. Both genes are part of a gene cluster on chromosome 12 that normally is maternally imprinted – meaning that only the gene copies inherited from the mother are expressed.

Examination of more than 60 iPSCs lines developed from several types of cells revealed that this gene cluster was silenced in the vast majority of cell lines. While the gene-silenced iPSCs were able to generate many types of mouse tissues, their overall developmental potential was limited. In an assay that produces chimeric animals that incorporate cells from two different stem cells, mice produced from gene-silenced cells had very few tissues that originated from the iPSCs. However, in a few iPSC lines the gene cluster was normally activated, and in the most rigorous developmental assay, those iPSCs were as successful in producing live animals as embryonic stem cells have been. The authors believe this is the first report of animals being produced entirely from adult-derived iPSCs.

"The activation status of this imprinted cluster allowed us to prospectively identify iPSCs that have the full developmental potential of embryonic stem cells," says Matthias Stadtfeld, PhD, of the MGH-CRM and HSCI, a co-lead author of the report. "Identifying pluripotent cells of the highest quality is crucial to the development of therapeutic applications, so we can ensure that any transplanted cells function as well as normal cells. It’s going to be important to see whether iPSCs derived from human patients have similar differences in gene expression and if they can be as good as embryonic stem cells – which continue to be the gold standard – in giving rise to the 220 functional cell types in the human body."

Hochedlinger adds, "Previous studies in mice have shown that embryonic stem cells derived from nuclear transfer – the technique used to clone animals – are indistinguishable from stem cells derived from fertilized embryos. Nuclear transfer is another way of reprogramming adult cells into embryonic-like cells, and comparing that approach with iPSC generation may yield important insights into ways of producing the safest and highest quality pluripotent cells for use in patients." Hochedlinger is an associate professor in the Harvard University Department of Stem Cell and Regenerative Medicine.

The home page for the portal is: http://www.cirm.ca.gov/stem_cell_education_portal

“Prop 71, through CIRM, has made California a fertile ground for stem cell science to take hold and flourish, but we will only realize the full potential of this burgeoning field by developing an educated workforce of the future,” said Senator Art Torres (Retired), co-vice chair of the Agency’s Governing Board. “Our first billion dollars in grants awarded is estimated to be on a trajectory to create tens of thousands of job-years of employment; we need to make sure we have the Californians trained to fill those positions.”

About CIRM: CIRM was established in November 2004 with the passage of Proposition 71, the California Stem Cell Research and Cures Act. The statewide ballot measure, which provided $3 billion in funding for stem cell research at California universities and research institutions, was overwhelmingly approved by voters, and called for the establishment of an entity to make grants and provide loans for stem cell research, research facilities, and other vital research opportunities. To date, the CIRM governing board has approved 328 research and facility grants totaling more than $1.02 billion, making CIRM the largest source of funding for human embryonic stem cell research in the world. Estimates suggest that these grants already awarded will generate tens of thousands of job-years of employment in the state.

Health Policy Committee senators are listed below. To find your district, please go to: http://www.senate.michigan.gov/2003/senatedistricts.pdf<https://remote.byrumfisk.com/exchweb/bin/redir.asp?URL=http://www.senate.michigan.gov/2003/senatedistricts.pdf>. Then look at the attached senate list to see which senator corresponds to your district.

 *   Sen. Tom George, chair: (517) 373-0793; sentgeorge@senate.michigan.gov<mailto:sentgeorge@senate.michigan.gov>
 *   Sen. Jason Allen: (517) 373-2413, senjallen@senate.michigan.gov<mailto:senjallen@senate..michigan.gov>
 *   Sen. Hansen Clarke: (517) 373-7346, senhansenclarke@senate.michigan.gov<mailto:senhansenclarke@senate.michigan.gov>
 *   Sen. John Gleason: (517) 373-0142; senjgleason@senate.michigan.gov<mailto:senjgleason@senate.michigan.gov>
 *   Sen. Gilda Jacobs: (517) 373-7888, sengjacobs@senate.michigan.gov<mailto:sengjacobs@senate.michigan.gov>
 *   Sen. Bruce Patterson: (517) 373-7350, senbpatterson@senate.michigan.gov<mailto:senbpatterson@senate.michigan.gov>
 *   Sen. Alan Sanborn: (517) 373-7670, senasanborn@senate.michigan.gov<mailto:senasanborn@senate.michigan.gov>

Lisa Hughes
Senior Director, Policy and Advocacy
Prevent Cancer Foundation
1600 Duke Street
Alexandria, VA 22314
301-466-8581 (cell)
703-519-2118 (direct)
lisa.hughes@preventcancer.org<mailto:lisa.hughes@preventcancer.org>