The California Institute for Regenerative Medicine (CIRM) was brought into existence by the passage of Proposition 71. Note the word "Regenerative." It is essential to understanding the intent of Prop 71 and how it was sold to the voters. The name of the agency was not an afterthought: it was stipulated in the first sentence of the enabling constitutional amendment: "There is hereby established the California Institute for Regenerative Medicine."
Proposition 71 was meant to promote research using stem cells, most significantly human embryonic stem cells. Stem cells can be employed in biomedical research in different ways. The most exciting and most heavily-promoted potential application was (and is) using these cells to regrow or create replacement tissue for damaged organs or nerves: to "regenerate" these tissues. Here is how the argument that was put forward in favor of Prop 71 in the official voter information guide begins: "stem cells are unique cells that generate healthy new cells, tissues, and organs. Medical researchers believe stem cell research could lead to treatments and cures for many diseases and injuries . . . ."
Now let's look at the intent of Prop 71 as spelled out within the actual text of the law. From the Findings and Declarations: "the California Stem Cell Research and Cures Act will . . . [establish] an institute which will issue bonds to support stem cell research, emphasizing pluripotent stem cell and progenitor cell research and other vital medical technologies, for the development of life-saving regenerative medical treatments and cures" (emphasis mine).
In short, the intent of Proposition 71 was crystal clear. Californians agreed to pay for stem cell research and especially the development of "regenerative medical treatments and cures." Why, then, has CIRM awarded almost $100 million for relatively conventional, non-stem-cell cancer research? Is this because the stem cell program has so far failed to yield new therapies? Is CIRM is so eager to make good on its promises that it's willingly ignoring the intent of the law that created it?
You can find the words "stem cells" in the titles and the abstracts of the cancer research to which I'm referring, but don't be fooled. Cancer stem cells are not the stem cells or pluripotent/progenitor cells referred to in the law or in the advertising for Prop 71. Cancer stem cells can have some of the same characteristics and molecular properties as stem cells and they may perhaps arise from normal progenitor cells, but they are abnormal and, unlike stem cells, cannot form normal tissues: rather, they yield malignancies and are thought to underlie disease relapses. They have no use in regenerative medicine. Research into cancer stem cells is conventional in several senses. First, as has always been the case with cancer, the goal is to find therapies to kill the malignant cells or at least get them to stop dividing--for example by inhibiting enzymes called kinases or targeting proteins on their surface--while leaving normal cells as unperturbed as possible. This type of research is widespread in academia, pharma and biotech and has never been subject to federal restrictions. The NIH has been funding research involving cancer stem cells since at least 1999. Of note, Iriving Weissmann, a big proponent of Prop 71 and recipient of Prop 71 funds for cancer stem cell research (most recently a nearly $13 million award focused on leukemia), has been receiving NIH funding for research into cancer stem cell-related therapies since at least 2009.
Funding of cancer stem cell therapy is not aligned with the intent of the law and has never been subject to NIH restrictions. Adult stem cells, stem cells, progenitor cells and pluripotent cells--the cell types that are are the focus of the law--are defined in Article 3. Cancer stem cells do not fall under any of these categories.
Now delving further into the letter of the law: consistent with law's intent, the section describing how research funding is to be awarded stipulates that "a high priority shall be placed on funding pluripotent stem cell and progenitor cell research that cannot, or is unlikely to, receive timely or sufficient federal funding, unencumbered by limitations that would impede the research. In this regard, other research categories funded by the National Institutes of Health shall not be funded by the institute." Cancer stem cell research is not pluripotent stem cell or progenitor cell research, there are no restrictions on cancer stem cell funding, and the NIH has funded many grants looking at cancer stem cells in one way or another.
A provision of the law allows non stem-cell research to be funded "if at least two-thirds of a quorum of the members of the Scientific and Medical Research Funding Working Group recommend to the ICOC that such a research proposal is a vital research opportunity." The Review Summaries from the Scientific and Medical Research Funding Working Group are available online (e.g., see here). There is no indication that consideration was given to the fact that the projects are outside the intended scope of the law nor is there reasoning provided why they should nevertheless be funded as "vital research opportunities." Of equal importance, there is no indication that the required separate votes were taken and resulted in the stipulated two-thirds super-majorities.
In the latest funding announcement from CIRM, half of the awarded applications and approximately half of the $60 million in awarded funds went to such non-stem cell (cancer stem cell) projects. Other projects within the intended research scope of the law were passed over.
CIRM, perhaps feeling pressure to live up to its initial hype, seems to be disregarding the intent of Prop 71 (as spelled out within the law itself).
Unless the required votes are being taken recommending the cancer stem cell projects as "vital research opportunities," CIRM may be operating unlawfully. I am unable to find any mention of these votes and the required two-thirds outcomes in the publicly-available documents on the CIRM website. I do not understand how, if these procedures are not being followed, CIRM can be said to be acting in a lawful manner.
Should CIRM be backing away from the riskier, much less further advanced stem cell research it was created to advance in favor of cancer research? Should we expect CIRM to adhere at least to the letter of the law if not the intent?
UPDATE: more on the two-thirds vote requirement in my next post.
ANOTHER UPDATE: David Jensen may look into these issues.