Follow up on "Obama's Ethics Tough On Approval of New Stem Cell Lines"

The NIH has rejected 47 stem cell lines carrying a variety of disease causing mutations reports the Chicago Sun-Times.  The lines developed from preimplantation genetic diagnosis at the Reproductive Genetics Institute failed to receive the "OK" for federal funding because of a problem in the patient consent form.  I reported on the initial controversey in a post a few weeks ago.

The lines are potentially a gold mine for researchers studying the relationship between the mutated gene and the development of diseases such as muscular dystrophy and huntington's disease.  The stem cell lines will not be available for federally funded research and studies utilizing these lines must now be funded soley through private resources.

Obama's Ethics Tough On Approval of New Stem Cell Lines

On March 9, 2009, President Barack Obama issued Executive Order 13505, entitled Removing Barriers to Responsible Scientific Research Involving Human Stem Cells.  This was the order that over turned the much maligned Bush restrictions on federally funding human embryonic stem cells research.  Most researchers in the field thought that better times had come, and in most instances they have.  However, The NIH was mandated with the task of setting forth ethical guidelines that new stem cell lines must meet in order to receive federal funds.  This has much to do with the patient informed consent process, a sometimes tricky ordeal of getting the proper verbiage and language in a signed document, and not with the actual science of stem cells.

The USA Today has run a great article on how tough these ethical guidelines are to meet in some instances and what the cost to science is for those lines that do not meet the standards.

For a decade, Oleg Verlinsky and colleagues at Chicago's Regenerative Genetics Institute created human embryonic stem cells marked with these diseases and others — made from embryos donated by suffering families — hoping to combat these illnesses.

On Thursday, A National Institutes of Health panel ruled one sentence of legal language in the consent form used by RGI meant these hundreds of cell "lines", or colonies, shouldn't receive federal research funding. "They will remain frozen, or discarded, forever," Verlinsky says. "Without federal support, no one will use them for research."

The trouble came from a sentence at the end [of the patient consent form], "We further agree that we, our heirs, successors, relatives, representatives, and/or agents will not bring any action in law or in equity, or in any administrative setting, related to our participation in this study."

That's "exculpatory" language, which waives a patient's rights to sue for negligence or harm, 4 of the 5 ACD panel members agreed, something forbidden under the federal "Common Rule" governing research. One panel member suggested the sentence only applied to lawsuits over profits from any "Patents and Discoveries" made from the cells, but was outvoted.

"There were some enterprising lawyers who probably felt that language needed to be in the consent and didn't appreciate what it might mean," Collins said, at the meeting. "But if we have guidelines, we have to stick to them in order to maintain their credibility." NIH has yet to issue Collins' final decision on the panel's guidance, which recommended approval for the six lines from other institutions.

Many people have asked me lately about the effects of lifting the Bush restrictions and the Obama Administration's support for stem cell research.  While Obama's executive order has been a great thing for the field of stem cell biology and regenerative medicine, It shouldn't be taken to mean that it is now easy to do this research. We can't just go running through the streets doing anything we want with stem cells and human embryos.  It is still a heavily regulated field in which rigorous ethical guidelines must be followed.   Progress is being made, albeit slowly, and we are doing it in an ethical and responsible manner.

California stem cell research: Were voters duped? - latimes.com

Today, the LA Times ran the story California stem cell research: Were voters duped?  It points out the intense criticism that has developed against all the hype surrounding the $3 billion proposition but also acknowledges that science moves slow and the huge challenges that encompass stem cell research. For once the author even calls out the media for hyping the ever caution but optimistic researcher statements.

...the California Institute for Regenerative Medicine, created by that 2004 ballot initiative, has handed out more than $1 billion in research funding. But there have been no "miracles" — no paralyzed people abandoning their wheelchairs or diabetics throwing away their needles. There hasn't even been a human trial of embryonic stem cells, those amazing shape-shifters that can grow into any cell in the body.

So were Californians duped?

Some would say yes. "There have been no cures, no therapies and little progress," Investors Business Daily complained in an editorial earlier this year. Rush Limbaugh went further, declaring embryonic stem cell research "fraudulent, fake."

It's no surprise that the initiative's proponents made big promises: They had something to sell. But instant miracles are uncommon in science, and journalists should do a better job making that clear. We need to highlight the uncertainties in science and, in medical quests such as stem cell therapies, emphasize the baby steps involved that in fact are big leaps: reproducing and growing these flexible cells, understanding how they work, using them to learn about disease, designing treatments and then testing the safety of any resulting therapy.

It will take many more years before we see the fruits of the California endeavor in our clinics, hospital labs, and pharmacies.  There is no question though that this science is some of the most exciting technology that humans have developed.  So, keep in mind, did computers revolutionize our lives overnight?

Stem cell biology challenges traditional view of tumorigenesis

A very interesting aspect of stem cell biology is the hypothesis that stem cells and progenitors may be the origin of some cancers.  Below is an excerpt from the research group web page of Dr. Eva Hernando.  I believe this sums up the current views on this subject quite nicely.

Traditionally, mature cells in specific tissues and organs have been regarded as the cell-of-origin of the corresponding tumors. However, the observation that tumor cells need to accumulate genetic and phenotypic alterations over extended time periods has turned the view in recent years to stem cells or progenitors with a prolonged lifespan, broadly distributed in local reservoirs [1]. These cells, in charge of maintaining tissue homeostasis, are now considered as the potential target of neoplastic transformation.

Although this notion has been largely accepted for certain leukemias and lymphomas in which the corresponding hematopoietic progenitors are precisely defined, this theory has not yet permeated the field of solid tumors, with few exceptions [2-4]. The identification of maturation stages in non-hematopoietic (i.e., epithelial, mesenchymal) cell types is proving difficult due to the lack of distinctive markers and the low abundance of such intermediates in adult tissues, except after trauma-induced regeneration.

Our laboratory is studying whether certain sarcomas originate from mesenchymal progenitors [5, 6] and whether melanomas result from transformation of melanocytic precursors [7, 8]. Moreover, we hypothesize that alterations in the normal differentiation process of these progenitors act at early stages of tumor initiation, and that the retention or reactivation of stem cell properties may contribute to tumor progression and aggressive behavior (resistance to therapy, metastasis). A limitation for these studies is our partial understanding of the normal differentiation process of these two lineages.

The stem cell state and the process of differentiation are regulated in part by signalling pathways, many of which are a function of kinase activity.  Will we be able to target these stem cell specific pathways with small molecule inhibitors to prevent cancers?