Written Public Comment to REGULAR MEETING OF THE TASK FORCE ON NEUROSCIENCE AND MEDICINE OF ICOC CIRM

Written Public Comment to REGULAR MEETING OF THE TASK FORCE ON NEUROSCIENCE AND MEDICINE OF THE INDEPENDENT CITIZENS OVERSIGHT COMMITTEE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE Organized Pursuant To The CALIFORNIA STEM CELL RESEARCH AND CURES ACT on October 18, 2023

CIRM ICOC board member Larry Goldstein who was UCSD stem cell center director has certainly known that induced pluripotent adult/stem cell (iPSC) is a fraud or scam since the beginning. They even published a paper in a top scientific journal to show the genomic instability and cancer risk of iPSC to try to overturn iPSC as pluripotent stem cells and the alternative of pluripotent human embryonic stem cells (hESC), but unsuccessful. However, Larry Goldstein also received millions of NIH and CIRM iPSC grants, acting like a hypocrite. CIRM President’s mentor Irving Weissman would not have Stanford University to pay the State ~$15 million in Jan. 2022 for their involvement in iPSC Ponzi scheme that fast if he did not know iPSC was a fraud or scam. Irving Weissman’s student Fred Gage of Salk Institute would not insist on only doing iPSC modeling for diseases, not going into clinical trials, if he did not know that iPSC was in fact cancer cells and believe that iPSC disease modeling was the “lesser of two evils” choice. However, none of those stem cell center directors and prestigious professors would raise any questions and safety concerns about iPSC based on their scientific knowledge, their expertise, even their conscience, if their funding or their money was at stake. CIRM, with the Chair and President paid more than the Governor, after having spent $ 4 or 5 billion of CA taxpayer money, still could not figure out any opportunities exist for generating high-impact research results and high burdens of diseases, really?!!! What a shame! A well-known scientific fact about cancers is that cancer cells have lost their ability to differentiate. iPSC-derived neurons do not even look like neurons. However, after 9 or 10 meetings of the CIRM task force on neuroscience and medicine for over 2 years, all Larry Goldstein could come up is a conflict-of-interest plan to model neuropsychiatric diseases with iPSC to best serve his own special interest groups, including Fred Gage and his students (e.g., UCSD stem center director Alysson Muotri). One of the fatal flaws of immunotherapy that none of the immuno-oncology companies would tell the public is that immunotherapy is extremely ineffective, only kills < 1% of cancer cells, and cancers are well known for reoccurrence if only one cancer cell is not killed. Irving Weissman, the Stem Cell Center Director of Stanford University, of course knows that, and of course he also knows the basic scientific facts that CD47 – the “do not eat me” signal -- is a common cell surface ligand expressed on both healthy and cancer cells, and CD47 antibody attacks not only cancer cells, but also stem cells of vital organs, making it highly toxic to patients. However, he still had CIRM President back his Company Forty Seven with $15 million of taxpayer money, which allowed him to sell Forty Seven to Gilead Sciences for $4.9 billion that had generated $67 million for Stanford and $191 million for himself in March 2020. In July this year, Gilead Sciences had to eat the loss of $4.9 billion and end Phase 3 trial of the CD47 antibody of Forty Seven since it is unlikely to improve survival, after multiple clinical holds for over a year, which have raised some serious questions about how Forty Seven could even pass Phase 1 safety trial with the $15 million from CIRM if they did not falsify or fabricate data in CIRM-funded research and clinical trials, after previous $40 million from CIRM to Irving Weissman’s other Company Stem Cell without any competition had produced absolutely nothing. Of course, the public would not hear anything even slightly mentioned about such failed clinical trials that CIRM has pumped into hundreds of millions of taxpayer dollars in CIRM press releases, and CA taxpayers end up having to eat the losses too. Who have actually profited from the loss of taxpayer dollars, profited from deliberately harming patients, profited from intentionally defrauding the investing public in the staggering amounts of hundreds of millions, even billions?

Written Public Comment to REGULAR MEETING OF THE TASK FORCE ON NEUROSCIENCE AND MEDICINE OF THE INDEPENDENT CITIZENS OVERSIGHT COMMITTEE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE Organized Pursuant To The CALIFORNIA STEM CELL RESEARCH AND CURES ACT on October 18, 2023

Dear TASK FORCE ON NEUROSCIENCE AND MEDICINE OF ICOC CIRM,

Thanks for the meeting notice and thank you for this opportunity to present my Public Comment in writing. I’d like to make a public comment regarding your meeting agenda:

• Do opportunities exist for generating high-impact research results?
• Should CIRM focus on diseases with “high burdens?” 
• Should the agency emphasize research whose results will cut across multiple diseases?

First of all, CIRM portfolio analysis presentation only shows neuro profile by diseases, but not by types of stem cells. If diseases are like the enemy, stem cells are like the weapon to arm us for the enemy. In the war against diseases, if you do not have the weapon, how are you going to kill the enemy? If you do not have the stem cell, how are you going to fight the disease? In the war against diseases, if you do not have a high-impact weapon, how are you going to generate high-impact research in the battle field? If you do not have highly-capable and scalable stem cells to restore the lost tissue and function, how are you going to relieve the high burdens of diseases? California Institute for Regenerative Medicine (CIRM) was established and has been sustained by The CALIFORNIA STEM CELL RESEARCH AND CURES ACT to fund stem cell research to find and build the high-tech weapon to fight diseases and relieve the high burdens of diseases, not disease research to figure out what the enemy is. In other words, in the war against diseases, CIRM is the weaponry, not a disease factory. Why wouldn’t CIRM portfolio analysis show neuro profile by types of stem cells?

Like weapons, there are many types of stem cells. There are human embryonic stem cells (hESC), non-functional pluripotent stem cells, functional stem cells, somatic stem cells, multipotent stem cells, tissue-specific stem cells, tissue-resident stem cells, neural stem cells, neuronal progenitor cells, cardiac stem cells, cardiac precursor cells, lung stem cells, liver stem cells, mesenchymal stem cells, etc. There are also cancer stem cells and cancer cells that are falsely called stem cells, e.g., induced pluripotent adult/stem cells (iPSC) that are in fact adult cells reprogrammed with oncogenes or cancer cells harboring oncogenes.

Different stem cells have different proliferation and differentiation capabilities. The traditional sources of engraftable human stem cells for transplantation therapies have been multipotent human somatic stem cells isolated directly from the tissue or organ system of interest. However, cell therapies based on tissue-derived/resident stem cells have encountered supply restriction and difficulty to use in the clinical setting due to their limited expansion ability in culture and failing plasticity after extensive passaging. Pluripotent hESC can maintain long-term, stable growth and differentiate into clinically-relevant lineages, providing an inexhaustible source of replacement cells for human tissue and function restoration. However, how to channel the wide differentiation potential of pluripotent hESC efficiently and predictably to a desired phenotype has been a major challenge for both developmental study and therapeutic application. Developing innovative, reproducible, scalable technologies to turn pluripotent hESC into a large supply of disease-targeted lineage-specific cells, such as neuro cells for a wide range of incurable or hitherto untreatable neurological diseases, insulin-secreting cells for treating diabetes affecting 250 million people, liver cells for liver diseases, lung cells for lung diseases, is vital to harnessing the power of hESC for safe and effective clinical translation.

A host of neurological disorders, including stroke, Parkinson’s disease (PD), Alzheimer disease (AD), spinal cord injury (SCI), traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) are major health problems with estimated costs of over $2 trillions annually world-wide. Those devastating and life-threatening diseases are leading causes of death or permanent disability, but there is no effective treatment or drug that can restore the damaged or lost neurological tissues and functions. Millions of people are pinning their hopes on stem cell research. The limit capacity of neuron circuitries of the brain and spinal-cord for self-repair constitutes a significant challenge to traditional medicine for tissue and function restoration in seeking cures for those serious, devastating, or life-threatening diseases and conditions. To date, the need to restore vital tissue and function for a wide range of incurable or hitherto untreatable neurological diseases remains a daunting challenge to the conventional mode of drug development. Although stem cell therapy represents a promising regenerative medicine approach closest to provide a cure for those diseases, demonstrating stem cell production at the scale and product purity adequate to heal the damaged or lost tissues that have naturally limited capacity for repair, such as the human heart and brain, has been a big challenge for traditional adult stem cell sources or products. Innovative hESC technologies provide the only therapeutic solutions for a wide range of incurable or hitherto untreatable neurological diseases and a practical scalable solution for CNS regeneration.

Most neurological disorders have neurological tissue and function damages or losses. To find treatments or cures, to fight diseases, we need a high-tech weapon that is scalable and that can restore the damaged or lost neurological tissue and function. hESC provide that high-tech weapon with the capability and scalability of generating a large supply of neurons to restore the lost neurological tissue and function. No mesenchymal stem cells, no CNS or tissue-derived neural stem/progenitor/precursor cells, no iPSC, no any other stem cells in CIRM portfolio can generate a large supply of neurons to meet the challenge. The neurons derived from iPSC shown by psychiatry professors, like Christine Cheng of UCSD, shown by all those iPSC professors, and shown by over $300M investment of CIRM grantees, do not even look like neurons, only very weakly express one single neuron marker, it is very questionable what kind of insight or useful knowledge could be generated from iPSC, considering iPSC is in fact adult cells reprogrammed with oncogenes or cancer cells harboring oncogenes, a scarlet “Red” adult stem cell Ponzi scheme of the Bush administration. A well-known scientific fact about cancers is that cancer cells have lost their ability to differentiate. iPSC is like a faulty weapon. If CIRM did a portfolio analysis by types of stem cells, we could see CIRM bet most of its money on a faulty weapon (e.g., iPSC) or obsolete weapons (e.g., mesenchymal stem cells of Brainstorm), which has not only generated no-impact research results that are falsified or fabricated, but also relieved no burdens of any diseases and generated no return of billions of CIRM investment.

CIRM was established and has been sustained by California Propositions with taxpayer money to fund hESC research. CIRM is compelled by California voters to fund hESC research in order to find treatments or cures for a host of disorders that destroy lives. Only pluripotent hESC provide the capability to develop the high-tech precision weapons for a wide range of incurable or hitherto untreatable neurological diseases, and hESC platforms and products will have broad applications for a wide range of incurable or hitherto untreatable neurological diseases, having tremendous economy and health impact and bringing enormous benefit to diverse CA population. Innovative hESC technologies present hESC as a novel, advanced therapeutic strategy for a wide range of incurable or hitherto untreatable neurological diseases, provide the high impact weapon to generate high-impact research across multiple neurological diseases, and ultimately, relieve the high burdens of diseases, and generate high-yield return for CIRM investment.