October 2020 Message from the Director
Is California funding of stem cell research no longer necessary? To the contrary!
We are now at the stage of stem cell research that both novel discoveries and their translation to real clinical trials are expanding rapidly…but may not in the future, as a little bit of [mis]information can be dangerous. Both discoveries and translation to clinical trials will be blocked if prop 14 doesn’t provide a California alternative.
By Irv Weissman
These past few weeks, I’ve been asked by thoughtful friends and relatives whether it was true that the reasons for California funding of stem cell research are in our past; and that they’ve received voting guidance and read newspaper opinion page advice that the agency created in 2004 called CIRM (the California Institute of Regenerative Medicine, funded by Prop 71) was no longer necessary.
As I looked into these guidances and advisories, I realized that there has been a lot of disinformation about CIRM mainly from groups that opposed it the first time, and others who supplied California newspapers with false information.
The disinformation largely is around the current status of stem cell research. Because stem cells are the only cells that make and maintain our complex tissues and organs, the best way to find them is by confirming a cell’s ability to form and maintain these precise compositions of many cell types. We and the community of stem cell researchers have found that each system—blood forming, brain-forming, gastrointestinal tract forming, etc—have their own stem cells that were responsible in fetal life to make the organs and in adult life to maintain the organs. When things go wrong, aberrant stem cells can cause the diseases that hamper and kill people.
Nearly every human tissue or organ stem cell to date has been discovered through the use of the fetal remains from elective or therapeutic abortions. They can’t be found in the remnants of miscarriages, as the tissues from them die during the miscarriage. How can one ethically obtain such tissues? In the late 1980s and early 1990s rules were established that enabled obtainment of viable fetal tissues. First, It is forbidden to provide any incentive for women to choose to have the abortion. After the procedure she decides whether the fetal remains could be discarded, or used for medical research. The woman having the abortion, the team doing the abortion, the agencies collecting and distributing the fetal remains cannot be compensated for their role in the process—make a profit—except for the logistical costs to obtain and distribute the tissue
With those protections in place even before CIRM, stem cell discoveries and therapies coming from them have led to therapies, or emerging therapies, or early clues to eventual therapies affecting hundreds of patients, some of which will affect millions of patients. Even today there is not a single tissue stem cell that could be discovered by test tube experiments. The Trump administration, over the objections of the NIH and HHS, last year placed a ban on the use of human fetal tissue remains in US government funded research, including a complete ban on any NIH funded trainees—our medical students, graduate students, and postdoctoral fellows—from carrying their research forward if they use such cells or tissues.
In 2004 the ban by the government was for embryonic stem cells, leading California families with family members having incurable diseases to form coalitions with biomedical scientists to try to carry forward research for their families using these cells.
These cells came from excess numbers of ‘blastocysts’ stored at in vitro fertilization clinics, which can be discarded also; there was no regulation against making and then discarding them. The cells in the blastocyst stage embryo—just 20-30 cells in all—can be grown in petri dishes with known factors that keep them at that early embryonic stage. Removing the factors that keep them embryonic allows the production of all cell types in the adult body, but not organs. Vice President Pence banned all ES research in Indiana when Governor, and a large fraction of the US congress has asked for a ban on government funding of all embryonic stem cell research.
So when the op-eds and guidances from groups state that stem cell research is fully and adequately funded by the NIH, and so proposition 14 should be voted down, either they didn’t question those who claimed it was funded, or were misinformed. Shame on them.
A final issue that has been claimed in the op-eds and guidances is that the original stem cell funding proposition that gave us CIRM, proposition 71, promised it would lead to cures of diseases in the 10 years of its allowed funding. That is simply untrue. I helped write and to speak out in public about how discoveries lead to therapies. Here is a precis of what I said:
Working back from the approval of a therapy by the FDA, it takes at least 3-5 years of what is called phase III clinical trials that are successful to get a therapy that is both safe and effective approved.
Before that it takes 2-4 years of phase II clinical trials to show hints of efficacy worthy to initiate phase III trials.
Before that it takes 1-4 years of phase I trials with different doses to prove safety of the therapy.
Before that the preclinical development of the therapy in animals and other investigations are required, and these take a minimum of 4 years, usually longer.
Before the preclinical development can begin, there is a preclinical proof of principle that the discovery can lead to a therapy or product that cures or treats animal models or tissue culture models of the disease; these usually take 3-5 years.
And, of course, before the preclinical proof of principle, there must be a discovery. When CIRM began, it mainly funded discoveries, or preclinical studies from an existing discovery.
So that is 13-20 years that are usually required to go from a discovery to an approved therapy.
That is why I said on the campaign in 2004, and last year in interviews with reporters from the newspapers who published the op-eds, to paraphrase,” it will be at least 15 years to go from discovery to therapy, and most discoveries don’t make it. Vote for this proposition so that your children and grandchildren can have a better chance for disease therapies that begin with funding this research. The federal government is banned from funding this field, and so it’s a state’s rights issue for California to provide that which the federal government will not provide.” That is as true today as it was in 2004.
NIH cannot fund research using fetal tissues; California can via CIRM.
NIH restricts and likely will ban funding of research using or making ES or ES like cell lines; California funds them now via CIRM.
NIH does not fund, or fund adequately, the entire set of phase I and II trials of any experimental agents or therapies; CIRM does.
NIH is subject to yearly congressional and executive branch redistributions of its funding by political actions, causing instability; CIRM works through 40 year bond funding, providing a guarantee of 10 years of stable funding for a field.
If you have friends or newspaper editorial staffs who claim we are past the time when California needs to fund this research, please ask them to provide evidence not surmise. I have seen and participated in research begun under CIRM already in clinical trials that have had remarkable outcomes so far. At this late stage in my career, I am deeply saddened that misinformation is closing avenues of therapies not funded or fundable by the federal government, as my children and grandchildren—and yours—will pay the price with diseases that might have been treated in the brief window of time when they could have been treated.