Public Record: Dr. Xuejun Parsons’ Response to OMB-2021-0005-0136
Public Record: Dr. Xuejun Parsons’ Response to OMB-2021-0005-0136: Office of Management and Budget’s (OMB) Request for Information (RFI) on Methods and Leading Practices for Advancing Equity and Support for Underserved Communities Through Government.
Dr. Xuejun Parsons’ Response to OMB-2021-0005-0136: Office of Management and Budget’s (OMB) Request for Information (RFI) on Methods and Leading Practices for Advancing Equity and Support for Underserved Communities Through Government.
Mission & Areas of Expertise: San Diego Regenerative Medicine Institute (SDRMI) & Xcelthera are founded to leverage stem cell technology and intellectual property (IP) to provide novel and advanced stem cell therapy for unmet medical needs that have been challenging to traditional medicine. In regenerative medicine, human embryonic stem cell (hESC) research holds huge promise for treating major human diseases that have been challenging to traditional medicine. Millions of people are pinning their hopes on hESC research. Xcelthera is a major innovator in stem cell research and uniquely holds exclusive rights for the key breakthrough stem cell technology – PluriXcel -- for the major bottlenecks in the regenerative medicine market (USPTO patent # 9,428,731; # 8,716,017), enabling large-scale production of high quality clinical-grade pluripotent hESC lines and their functional human neuronal and heart cell therapy products for commercial and therapeutic uses. PluriXcel provides innovative, scalable, and reproducible platforms to enable developing regenerative medicine advanced therapy (RMAT) for world-wide major health problems and ensure high degrees of efficacy and safety of the hESC-derived RMAT products, thus robust clinical benefits leading to therapies, which not only constitutes clinically representative progresses in both human neuronal and cardiac RMAT products for treating a wide range of incurable or hitherto untreatable neurological and heart diseases, but also offers manufacturing innovation for production scale-up and creation of replacement tissue/organ products.
The Area Sections Submission and Materials Support:
Area 1: Equity Assessments and Strategies: Systemic barriers for Asian-American women (AAW) to face to advance their careers to senior faculty levels; As an AAW, I have been systematically denied public investment opened up by my stem cell research breakthrough innovations, including entry level funding, by NIH flawed reviews behind closed-doors; Without diversity, equity, and inclusion (DEI), billions of the public funding for stem cell research have wasted on bogus stem cells, such as induced pluripotent adult/stem cells (iPSC) that are in face adult cells reprogrammed with oncogenes or cancer cells harboring oncogenes; The economic and funding disparities between the AAW and the white men are staggering; The behind-closed-doors initial peer review policies and programs in the public funding agencies have served as systemic barriers; To abolish the unaccountable, discriminative pre-application triage process in the initial peer review and establish transparent, engaged review system to monitor and fix flawed reviews and use quantitative metrics-based review criteria and guidelines to reduce systemic barriers; To close the big gap by establishing Career Advancement Diversity Award and Outstanding Achievement Diversity Award to provide major funding and create high-ranking jobs for AAW.
Area 2: Barrier and Burden Reduction: To lower the entry barriers, close the economic and funding gaps, and reduce the burdens for AAW by using criteria and achievement based direct entry level funding and seeding to advance DEI; To set aside 5% fund of every major funding opportunity and infrastructure award and mandate matching award for AAW; Form special emphasis panels and establish regulatory policies specifically for hESC.
Area 3: Procurement and Contracting: Mandate set-aside 5% infrastructure fund to seed and support the AAW-owned/founded small business of high priority to improving human health through procurement and contracting.
Area 4: Financial Assistance: To allocate financial assistance and set up the Diversity Service Award to outstanding AAW who have made breakthrough innovations to advance stem cell therapy with the transformative health projects, but have been blocked any funding opportunities by systemic inequality.
Area 5: Stakeholder and Community Engagement: To ensure fairness in decision-making, protect the American people’s interests, and maintain a high return of the public investment in research, it is crucial for major agencies, including NIH, FDA, HHS, to include a minority voice and have a minority view.
Area 1: Equity Assessments and Strategies:
1.1. Systemic Barriers for Asian-American Women (AAW) to Face to Advance Their Careers to Senior Faculty Levels and Leadership Positions
The distinctive combination of biases of race and gender – being Asian and being women -- plays a major role in blocking Asian-American women (AAW)’s career advancement and recognition in academia as well as in industry, and forces them into lower-paying jobs, lower-ranking positions, or even poverty that are disproportional to their higher educations, skills, achievements, and contributions. In the US, women are less likely than men to achieve tenure and hold high ranking positions, and are more likely to be found in lower-ranking academic positions; women of color are especially underrepresented in academia, and are also more likely to hold lower-ranking academic positions; Asian women held 5.3% of tenure-track positions, 3.5% of tenured positions, and 2.8% of professor positions [National Center for Education Statistics, IPEDS Data Center (2018)]. Technology and engineering are among the top sought-after skills in the US; however, a gender gap in science, technology, engineering, and mathematics (STEM) persists across the US; women are more likely to hold lower-paying STEM jobs; AAW are overall underrepresented in STEM, holding 5.3% of bachelor’s degrees and 6% of jobs across all STEM fields [Catalyst, Quick Take: Women in STEM (2020)]. The race and gender disparities of AAW become even more entrenched in prestigious academic appointments; AAW hold only 0.7% of endowed chair positions and 0% of distinguished professor positions [Hartlep et al, Asian/American Scholars of Education 21st Century Pedagogies, Perspectives, and Experiences, New York, NY, Peter Lang Publishing]. Women are much less likely to found companies in STEM fields; only 7% scientific advisory boards are female; Less than 11% of venture capital deals went to firms with a female CEO, and only 2% startup financing went to women, even though women are fully engaged as the entrepreneur and business owner [Overcome structural barriers for women in entrepreneurship: a workshop, NASEN Committee on Women in Science, Engineering, and Medicine]. As a woman-founder and Asian-American entrepreneur of regenerative medicine start-up, my experiences of persistent poverty and systemic inequity bear witness to such racial and gender discrimination and injustice.
I received my PhD in Biochemistry, Cell, and Molecular Biology from prestigious Cornell University of Ivy League and, following my PostDoc training in the field of molecular biology at University of California at San Diego (UCSD), I was awarded National Institutes of Health (NIH) grants for successful transition of my career into the stem cell field as the principal investigator (PI) and led the collaborative effort to develop the utility of human embryonic stem cells (hESC) as a model system for a diverse range of biological and medical problems in one of the NIH exploratory centers for stem cell research. I am the first to develop the key breakthrough technology – PluriXcel -- for the major bottleneck in the regenerative medicine market for large-scale production of high quality clinical-grade hESC lines and their functional human neuronal and cardiomyocyte cell therapy derivatives for commercial and therapeutic uses, which have generated intellectual property (IP) to enable developing regenerative medicine advanced therapy (RMAT) for unmet medical needs challenging traditional medicine [patents: USPTO# 8,716,017 & 9,428,731; selected publications: Parsons XH. Directing pluripotent hESC towards lineage-specific cell therapy derivatives for regenerative medicine. Gene and Cell Therapy: Therapeutic Mechanisms and Strategies, 2015, Chapter 31:795-818; Parsons XH. An engraftable hESC neuronal lineage-specific derivative retains embryonic chromatin plasticity for scale-up CNS regeneration. J. Reg. Med. & Tissue Eng. 2012, doi: 10.7243/2050-1218-1-3, PMID23542901, PMCID3609668; Parsons XH, et al. Genome-scale mapping of microRNA signatures in hESC neurogenesis. Mol. Med. Ther. 2013, doi: 10.4172/2324-8769.1000105, PMID23543894, PMCID3609664; Parsons XH. Human stem cell derivatives retain more open epigenomic landscape when derived from pluripotent cells than from tissues. J. Regen. Med. 2013, doi: 10.4172/2325-9620.1000103, PMID23936871, PMCID3736349; Parsons XH. MicroRNA profiling reveals distinct mechanisms governing cardiac and neural lineage-specification of pluripotent hESC. J. Stem Cell Res. Ther. 2012, doi: 10.4172/2157-7633.1000124, PMID23355957, PMCID3554249; Parsons XH. Direct conversion of pluripotent hESC under defined culture conditions into human neuronal or cardiomyocytes cell therapy derivatives. Methods Mol. Biol. 2016, doi: 10.1007/7651_2014_69, PMID24500898]. I am the world’s top stem cell researcher and innovator, and own hESC patents critical for developing stem cell therapy for a wide range of incurable or hitherto untreatable heart diseases and neurological diseases important to improving human health and the missions of the NIH.
However, as an AAW, I have faced systemic barriers to advance my career to a tenure-track professor position in academia for which I am highly qualified, have been systematically denied equal opportunities to senior faculty levels matching my credentials and experiences, and have struggled to overcome systemic inequities to gain equitable access and recognition in a field dominated by men and to get promoted to a prominent and leadership position traditionally held by men. I have immense experiences and training in hESC research, process highly sought-after skills in STEM/Public Health/Health Sciences, have made ground-breaking achievements in stem cell research, have established independent and vigorous extramurally-funded research programs in regenerative medicine, and even won a NIH K01 Career Development Award with the career development goal set to sponsor me successful transition to becoming a tenure-track assistant professor in the Stem Cell field by the end of that award. However, as an AAW, I still could not even find a tenure-track assistance professor position in any US university or research institute to advance my career and continue my stem cell research, even though California passed $3 billion of Prop71 to create the California Institute for Regenerative Medicine (CIRM) to supposedly support my stem cell research. Although my NIH K01 award promised institutional support and career advancement, as a woman and Asian junior faculty, I was in an inferior position to be bullied and taken advantaged by my mentors, the peers, the center directors, and the department chairs, and had to go through the trouble and hardship of switching 3 institutions in order to complete the award.
Ever since, I have been looking for a tenure-track professor position for which I am well-qualified, but still could not get a job that will allow me to advance my career to a more senior, recognized, and leadership position. As the world’s top stem cell researcher and innovator with highly sought-after expertise, I have been trying to become a NIH reviewer for relevant grants for over 10 years, but I am still excluded from any NIH review panels, and my voice still cannot be heard in NIH. As an AAW, I have also been excluded from many stem cell research networks, advisory boards, and major scientific societies, such as the Alliance for Regenerative Medicine and the International Society for Stem Cell Research (ISSCR), where my expertise, vision, and voice are crucial to the direction and funding of stem cell research. ISSCR, under the misleading and control of the induced pluripotent adult/stem cells (iPSC) that are in fact adult cells reprogrammed with oncogenes or cancer cells harboring oncogenes --- the bogus pluripotent stem cells introduced by Bush administration as the alternative of hESC to circumvent the ethical issue of hESC --- even banned me present my hESC research breakthroughs. Without a voice to support hESC research in NIH and major scientific societies like ISSCR, without a balanced view for stem cell research in NIH and those societies, as a result, billions of public funding for stem cell research have gone to bogus stem cells like iPSC and non-effective adult stem cells like mesenchymal stem cells (MSC), but not to safe and effective hESC products, and the public investment in research has missed real opportunities to generate a high return, to improve human health, and to advance the frontiers of future medicine.
Systemic inequity has not only blocked my career advancement and continued funding, but also plunged me into persistent poverty and financial hardship. As a result, I was forced by Biomed Reality (BMR) to close my stem cell research lab, and valuable stem cell research equipment/facility brought by tax-payers’ money and precious life-saving human stem cells and therapy products developed with tax-payers’ money were destroyed by BMR. To add insult to injury, our mortgage companies, first Ocwen and then Specialized Loan Servicing (SLS), even gave us a hard time to seek financial assistance from HAMP programs, denied us the protections from the California Home Owner Bill of Rights, and tried to foreclose our house without giving us any fair options to modify the mortgage or even notifying us.
1.2. As an Asian-American Woman (AAW), I have been Systematically Denied Public Investment Opened up by my Stem Cell Research Breakthrough Innovations, including Entry Level Funding, by NIH Flawed Reviews behind Closed-Doors
In order to facilitate the transition of human stem cell research towards stem cell therapy to provide the next generation of cell-based therapeutic solutions for unmet medical challenges in world-wide major health problems, I had to found SDRMI to continue my stem cell research. In regenerative medicine, hESC research holds huge promise for treating major human diseases that have been challenging to traditional medicine. Millions of people are pinning their hopes on hESC research. My innovative achievement in stem cell research has demonstrated the direct pharmacologic utility and capacity of hESC therapy derivatives for human nerve tissue and heart muscle regeneration and, thus, has presented the hESC therapy derivatives as powerful RMAT products for a wide range of incurable or hitherto untreatable neurological and heart diseases, including heart disease and failure, Parkinson’s disease (PD), Alzheimer disease (AD), spinal cord injury (SCI), traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (AMS), and stroke. My exceptional pioneer studies have provided innovative, scalable, and reproducible platforms to ensure high degrees of efficacy and safety of the hESC-derived therapeutic products, thus robust clinical benefits leading to therapies.
My breakthrough innovations in the emerging technology of regenerative medicine and leadership in stem cell research have contributed to improving policy making for hESC research in the Federal Government, including the more relaxed NIH funding policy for hESC research and the FDA RMAT Designation Program to accelerate regulatory review/approval and patient access to new stem cell therapies, and have also opened up scores of funding opportunities for new frontiers of stem cell research and regenerative medicine, including the White House BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies); the NIH Common Fund; the NIH High-Risk High-Reward Program; the DOD Advanced Tissue Biofabrication Manufacturing Innovation Institute (ATB-MII) Initiative; NIH RFA-NS-13-007 Exceptional Unconventional Research Enabling Knowledge Acceleration (EUREKA) for Neuroscience and Disorders of the Nervous System (R01); NIH PAR-15-071 Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Pharmacodynamics and In vivo Efficacy Studies for Small Molecules and Biologics/Biotechnology Products (R61/R33); NIH RFA-RM-12-001 Stem/Progenitor Cell-Derived Human Micro-organs and -tissues (U18); NIH PA-09-249 Directed Stem Cell Differentiation for Cell-Based Therapies for Heart, Lung, and Blood Diseases (SBIR [R43/R44]); NIH PA-10-122 SHIFT Award: Small Businesses Helping Investigators to Fuel the Translation of Scientific Discoveries [SBIR: R43/R44]; NIH PAR-14-088 Direct Phase II SBIR Grants to Support Biomedical Technology Development; NIH PAR-13-094 Differentiation and Integration of Stem Cells into Developing or Damaged Tissues (R01); NIH PAR-21-233 Blueprint Neurotherapeutics Network (BPN): Biologic-based Drug Discovery and Development for Disorders of the Nervous System (U44); NHLBI Catalyze Program.
However, the systemic barriers have denied not only my career advancement, but also equitable access to and fair competition for the public funding for stem cell research. To accelerate the movement towards clinical development of novel and advanced stem cell therapy for the treatment of a wide range of neurological and cardiovascular diseases, I founded Xcelthera. I have been sending NIH my hESC proposals since 2010 as the woman-founder of SDRMI and Asian American entrepreneur of regenerative medicine start-up Xcelthera, including: NIH AAP, R43HL145867, NHLBI: Developing hESC-derived regenerative medicine advanced therapy (RMAT) for heart disease and failure (2018); NIH R44HL136037, NHLBI: Myocardial tissue-specific bioreactors for heart assembly from hPSC cardiomyocyte derivatives (2016); NIH R21NS100970, NINDS: In vivo efficacy studies of hESC neuronal derivatives of PluriXcel approach in stroke models (IGNITE, 2016); NIH R01HL127362, NHLBI: Molecular controls in hESC cardiomyocyte specification (2015); NIH R43NS078832, NINDS: Dopamingeric (DA) regeneration of Xcel prototypes of hESC neuronal cell therapy derivatives in vivo (2014); NIH R43HL114131, NHLBI, Myocardium regeneration of Xcel prototypes of hESC cardiomyocyte cell therapy derivatives in vivo (2014); NIH R01HD079550, NICHD: Differentiation and integration of hESC neuronal progenitors in neurodegenerative developing CNS (2013). My projects enable clinical translation of hESC technology and IP for nerve tissue/heart muscle regeneration and neurological/contractile function restoration as much-needed RMAT for a wide range of neurological and heart diseases, having a groundbreaking impact on advance of medicine to provide newer and more effective RMAT for unmet medical needs that have been challenging to traditional medicine. The outcome of my projects will have a transformative impact on translational research priority by presenting hESC as a viable and robust therapeutic strategy for many devastating diseases, potentially shifting current research and clinical practices, and creating new scientific paradigms for tissue repair.
However, as an AAW from a woman-owned/founded minority small business, I have been systematically denied equal opportunities for a fair review of my proposals and participation in equal competition for the public funding for stem cell research. For over 10 years, NIH review committees and Special Emphasis Panels in the Center for Scientific Review (CSR) have systematically and intentionally biased the initial peer-review scores of my proposals to the bottom half for triage, and would not even bring any of my hESC research proposals up for a fair review by the entire study section. The reviewers’ comments in every single summary statement of my proposals were full of biases and factual errors, and even highly conflict-of-interest (COI) implicated, which indicated flawed reviews and none of the scores reflected the overall impact and scientific merit of any of my proposals, such as the scores for the significance unfairly, across-the-board low to even 8 or 9 (1 is the strongest and 9 is the weakest), considering that we proposed stem cell therapy for an unmet medical need that currently has no solution and the project will no doubt advance human health and dramatically improve quality of life; the scores for the innovation unfairly, across-the-board low to even 8 or 9, considering that we even own patents for the game-changing technology; the scores for the approach unfairly, across-the-board low to even 8 or 9, considering that this approach overcomes the major bottleneck in the regenerative medicine market, providing the only available human cell source in large scale and high quality for neuronal or heart muscle repair in the disease we target, is a highly likely breakthrough one, and we have established the technical feasibility and scientific merit of the project; the scores for the investigator unfairly, across-the-board low to even 8 or 9, considering that I am the world’s top stem cell researcher and innovator, highly trained in the proposed hESC research with inventorship and a record of grants, including NIH center grant and K01 award, to prove my training, and a track record of publications in internationally recognized peer-reviewed journals as the corresponding author, and my accomplishments have advanced the stem cell and regenerative medicine field by demonstrating the direct pharmacologic utility and capacity of hESC therapy derivatives for human CNS and myocardium regeneration and, thus, presenting the hESC therapy derivatives as powerful RMAT products for a wide range of incurable or hitherto untreatable neurological and heart diseases [please see samples of the Specific Aims of my proposals and NIH summary statements in the attachment]. Even though I addressed the reviewers’ comments in resubmission, the scores in none of my revisions significantly improved, and in most cases, were even worse with even more issues raised that were full of biases and factual errors or irrelevant or improper to assessing the fundability of the project. The NIH appeal system did not do the justice but only left repercussion on my future submissions. In most cases, I could not even get any responses from my NIH program officers (PO) who usually were unwilling to criticize the reviewers and correct the factual errors, biases, and the scores. As an AAW-founder and an innovator, after over 10 years of application for the public funding designated for stem cell research, I could not even obtain any entry level funding or early stage grant with my stem cell research breakthrough innovations to continue to advance the field, including NIH new investigator R01 when I was still fully eligible, IGNITE R21/R61, and SBIR Phase I, even though such entry level funding is for prototype development and proof of concept that I have done, even though NIH SBIR grant application guidelines specify Phase I does not require preliminary data and I have substantial preliminary data and have established the technical feasibility and scientific merit, even with the help of NIH application assistance program (AAP). As a result, I have been systematically denied not only equal funding opportunities and fair competitions, but also equitable access to financial and technical assistance programs and networks that are only available to NIH awardees, such as the Technical and Business Assistance (TABA) Program, I-Corps, NIH-funded resources like consultants, contract research organizations (CROs), expert NIH project managers and science officers, administrative supplemental financial assistance programs, and other SBIR assistance and support programs. In contrast, more than $20 M of the public funding, including Stem Cell Center Grant and Parkinson Center Grant, that involve my stem cell research but not my name, have gone into the hands of my mentors and center directors (all white men) with all sorts of financial and technical assistance programs and networks, and administrative supplemental financial assistance programs fully available to them. However, it was my original idea, my research, and my discovery, I developed and wrote the projects, even though they got that much money with my stem cell research, they still could not get anything done or make any progress without including me. I have made more progress and generated more inventions to advance stem cell research with my decimal NIH grants and limited resources. As an AAW-founder, I have been denied even the entry level funding, such as R21/R61 and SBIR Phase I, by NIH flawed initial peer review. In contrast, many white men holding high-ranking positions, such as the Dean of Harvard Medical School and the presidents and vice presidents of ISSCR, have benefited from millions and millions of the public funding opportunities opened up by my stem cell research breakthrough innovations, but still could not make any progress to advance stem cell research and therapy without the enabling technology I developed. As a woman-owned/founded minority small business, I could not even obtain any entry level funding to start my own lab with my breakthrough innovations in hESC research. In contrast, big universities and major institutes have procured hundreds of millions of the public funding to construct the regenerative medicine consortium facilities and expanding the fancy stem cell research buildings that are overwhelmingly occupied by those who are not even doing any stem cell research or even left empty, but inaccessible to woman-owned/founded small businesses.
1.3. Without Diversity, Equity, and Inclusion (DEI), Billions of the Public Funding for Stem Cell Research Have Wasted on Bogus Stem Cells, such as the Induced Pluripotent Adult/Stem Cells (iPSC)
Heart and neurological disorders are major health problems with estimated costs of over $2 trillion 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 heart or neurological tissues and functions. Millions of people are pinning their hopes on stem cell research. However, 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 cell sources or products. Derivation of hESC has brought a new era of cellular medicine for CNS and heart repair. The hESC are genetically stable with unlimited expansion ability and unrestricted plasticity, providing an unlimited source to deliver in the future a whole range of therapeutic treatments for tissue and function restoration in patients with life-threatening diseases and injuries. I have developed innovative human stem cell technology – PluriXcel -- that is safe and effective for human tissue and organ regeneration in the clinical setting, overcoming some major bottlenecks in the regenerative medicine market for tissue repair and biofabrication, offering currently the only available human cell sources in large quantity and high quality with adequate cellular capacity to regenerate the contractile heart muscle and the neuron circuitry. It not only constitutes clinically representative progresses in both human neuronal and cardiac therapeutic products for treating a wide range of incurable or hitherto untreatable neurological and heart diseases, but also offers manufacturing innovation for production scale-up and creation of replacement tissue/organ products. With such breakthrough innovations, with safe and effective hESC products developed for devastating and life-threatening diseases, however, as an AAW, I could not even procure any entry level funding, such as NIH R21/R61 and SBIR Phase I, to continue my stem cell research, to continue to do what I have been trained to do with tax-payers’ money, and to continue to do what I am good at, for over 10 years. In contrast, over the last decade, billions of the public funding for stem cell research have gone to bogus stem cells, such as iPSC and MSC, misled and controlled by those high-ranking, well-connected positions, such as the Dean of Harvard Medical School and the presidents and vice presidents of ISSCR.
hESC research is an immensely controversial and contentious field with lots of politics involved. To circumvent the ethical issue of hESC, the induced pluripotent adult/stem cells (iPSC) were introduced by Bush administration and some top scientists, including the vice president of ISSCR who ended up winning the Nobel Prize later on, as the alternative of hESC, over a decade ago. However, iPSC are in fact pluripotent cancer cells, cannot serve as the alternative of hESC. We all know embryonic genes abnormally expressed in adult cells are called oncogenes, and oncogenes cause cancer. What are iPSC? iPSC are adult cells abnormally expressing embryonic genes or artificially engineered to express embryonic genes, or in fact rightfully known as oncogenes in adult cells. One essential aspect of stem cells is their long-term genetic stability. Stem cells can maintain long-term, stable growth in culture, while cancer cells grow abnormally crazy and mutate fast. The iPSC papers were actually published in top scientific journals, such as Nature, Cell, and Science, in lightning speed, or only a few weeks, without any scientific evidences or data to show the long-term genetic stability of iPSC or iPSC could maintain long-term stable growth. Without the data of long-term genetic stability, the line between stem cells and cancer cells is bleared. For years, I have been trying to say why we should incorrectly call iPSC stem cells, while everywhere else in the scientific world such cells are correctly called cancer cells. However, as an AAW, my voice has been silenced in the public funding agencies, such as NIH and CIRM, and major scientific societies, such as ISSCR. In fact, human iPSC have been reportedly associated with abnormal gene expression, accelerated aging, and immune-rejection following transplantation owing to introducing foreign oncogenes and instability/abnormality to the adult genome [Zhao T, et al. Immunogenicity of iPSC. Nature 2011;474:212-15; Kim K, et al. Epigenetic memory in iPSC. Nature 2010;467:285-290; Gore A, et al. Somatic coding mutations in human iPSC. Nature 2011;471:63-7; Feng Q, et al. Hemangioblastic derivatives from human iPSC exhibit limited expansion and early senescence. Stem Cells 2010;28:704-12], and serious spontaneous mutations, the sign of cancer cells, have been identified in human iPSC clinical trials [Trounson A & DeWitt ND. Pluripotent stem cells progressing to the clinic. Nat. Rev. Mol. Cell Biol. 2016;17:194–200]. iPSC and hESC are not the same, and hESC technology and discovery do not automatically apply to iPSC, and in fact never work for iPSC. But those iPSC people won the Nobel Prize, published in top scientific journals, and are some powerful people, such as the Dean of Harvard Medical School and the presidents and vice presidents of ISSCR. Over the last decade, those high-ranking, well connected iPSC people have been blearing the line between iPSC and hESC, falsely claiming iPSC and hESC are identical, and using their high-ranking positions, connections, and high powers to suppress any open debates and bully any dissident voices. Without ensuring a diverse voice, without DEI, as a result, such obviously flawed conceptions and bogus iPSC have dominated the public funding agencies, such as NIH and CIRM, and major scientific societies, such as ISSCR, for over 10 years, and billions of tax-payers’ money have wasted on bogus stem cells.
1.4. The Economic and Funding Disparities Between the Asian-American Women (AAW) and the White Men are Staggering
The numbers of economic and funding disparities are staggering. As an Asian American junior faculty, I obtained ~$ 1 M total NIH funding for hESC research that allowed me to make breakthrough innovations for stem cell research. CIRM was created by California voters to specifically fund hESC research I was doing. However, with such achievements and contributions, as the AAW-founder of a small business, I could not even obtain any funding from NIH and CIRM to continue my stem cell research, to keep my stem cell lab open and the hESC therapy products I developed with NIH funding alive. In contrast, the Stem Center Director of UCSD has received > $20 M of CIRM funding without having to make any breakthrough innovation to advance stem cell research; the Stem Cell Center Director of Stanford University has received > $30 M of CIRM funding and > $20 M of NIH funding, and additional ~$40 M of CIRM funding for his company; the Dean of Harvard Medical School has received > $35 M of NIH funding, and wasted > $20 M on the bogus iPSC; the president of ISSCR and founder of Fate Therapeutics has received > $30 M of NIH funding and his company has received > $50 M of venture capital investment, even though they are using the bogus iPSC [https://report.nih.gov, https://www.cirm.ca.gov/grants]. Those high-ranking, well-paid, and well-funded positions have one thing in common, they are all white men.
I have made significant progress to advance our understanding of the molecular determinants of hESC fate restriction that is vital for evaluating their therapeutic potential, and have demonstrated the openness of pluripotent epigenome differentiates the active pluripotence of normal stable hESC from the repressive pluripotence of abnormal reprogrammed iPSC and cancer cells, however, as an AAW, I could not even obtain an entry level NIH funding, such as a new investigator R01, R21/R61 to continue my stem cell research and keep my stem cell lab open and precious human stem cells derived from embryos alive. In contrast, the Dean of Harvard Medical School requested even ~ $10 millions more from NIH to do more genomic analysis and comparison of iPSC and hESC after he was questioned about his dubious claim that iPSC and hESC were identical. Of course, his $ 10 millions of NIH funding concluded that iPSC and hESC are identical, even though iPSC are genetically-engineered adult cells harboring multiple oncogenes and hESC are not and originated from the opposite end of human development, the human embryos, even though the genomic data of identical twins would not be identical, even though if he could not find any difference, it might be only because he did not look into the right place, such as the epigenomes of those cells, it does not prove iPSC and hESC are identical.
Despite that my hESC proposals are cutting-edge, transformative health projects, high risk and high reward programs that should be funded by NIH Common Funds, as an AAW, I have been systematically denied fair review and equitable access to designated NIH Common Fund, and could not even obtain an entry level funding, such as SBIR Phase I (~250 K) or R21/61, with my breakthrough hESC technology and effective hESC products for life-threatening diseases. Despite that I develop stem cell therapy designated for FDA RMAT Designation Program to accelerate regulatory review/approval and patient access, FDA even systematically denied my pre-IND meeting requests in the name that we do not have GMP facility. In contrast, even though iPSC are genetically engineered cells harboring multiple oncogenes and showing seriously adverse effects in patients, the iPSC products of those high-ranking, well-connected positions and their companies have been well-funded by NIH, including NIH Common Fund, and even given the green light by FDA to advance clinical trials to market, including FT819, an iPSC-derived NK cell product by Fate Therapeutics that was founded by the renowned Harvard professor and the president of ISSCR.
Over the last decade, iPSC have been well-funded by NIH and CIRM, which has produced many bogus iPSC papers in top scientific journals and ISSCR’s official journals, such as Cell Stem Cell and Stem Cell Report, including bogus claims that they could even make human organs from iPSC. Those bogus iPSC papers automatically assumed that iPSC and hESC were identical without even doing any experiments or providing any data, and none of those iPSC papers did anything to check the genetic stability of their iPSC products. Those top scientists, including the Dean of Harvard Medical School and the presidents/vice presidents of ISSCR, are actually experts and mostly renowned professors in molecular biology with full knowledge that such concepts of iPSC are flawed and iPSC are bogus, but still, they have used their high-ranking positions, influences, and connections to back and promote iPSC as the alternative of hESC for their own financial gains, including millions and millions of NIH and CIRM funding to themselves and pumped-up stocks of their own companies. Funding iPSC is in fact a world-class fraud and staggering waste of tax-payers’ money in billions, and has generated nothing to advance medicine and improve human health, but mistrust and negative image for the public funding agencies. Without DEI, the public funding has been overwhelmingly dominated by bogus stem cells like iPSC and MSC, the credibility of the public funding agencies has been shaken, and the legitimacy of the government-funded stem cell research and RMAT has been tarnished.
1.5. The Behind-Closed-Doors Initial Peer Review Policies and Programs in the Public Funding Agencies have Served as Systemic Barriers to Equal Opportunity and Fair Competition for the Federal Funding and Assistance Programs, Resulting in Staggering Economic and Funding Disparities
Xcelthera is a major innovator in the stem cell research and regenerative medicine market, uniquely holding the exclusive rights for the key breakthrough stem cell technology – PluriXcel -- for well-controlled high efficient direct conversion of hESC at the pluripotent stage by small molecule induction uniformly into a large supply of high quality human neuronal progenitor cells (Xcel-hNuP) or heart precursor cells (Xcel-hCardP) with adequate neuronal or heart muscle regenerative potential for effective graft-dependent nerve or heart muscle repair, offering currently the only available human therapeutic cell sources in large quantity and high quality with adequate cellular capacity to regenerate the neuron circuitry and the contractile heart muscle. Clinical trials have identified the urgent need for an effective therapeutic cell source that can demonstrate stem cell production at the scale and product purity adequate to heal the damaged or lost nerve tissues or beating heart muscles in many life-threatening and devastating diseases. However, despite that Xcelthera provides that effective therapeutic cell source in urgent need, has demonstrated stem cell production at the scale and product purity adequate to heal the damaged or lost nerve tissues or beating heart muscles in those life-threatening and devastating diseases, overcomes major bottlenecks in the regenerative medicine market, even owns patents and exclusive rights for its technology and that effective therapeutic cell source, has established the technical feasibility and scientific merit, as the AAW-founder of Xcelthera, I could not even obtain an entry level grant, such as SBIR Phase I, to advance RMAT for those incurable or hitherto untreatable neurological and heart diseases after over 10 years of application.
NIH review committees and special emphasis panels in the CSR have been using the unaccountable and COI pre-application triage process by 3 (5 for IGNITE, CREATE-Bio, BPN) reviewers to systematically and intentionally bias the scores of my proposals to the bottom half, so that none of my proposals would be brought up for a full initial peer review by the entire study section. The CSR is supposed to be a peer-review system, and should hold the highest standard of integrity and transparency to ensure a continued high return on the public investment in research. However, the peer-review system of CSR has apparently been broken, as evidenced by the CSR reviewers’ comments in every single summary statement of my proposals for over 10 years were full of biases and factual errors, and even highly COI implicated, which indicate that every single initial peer review of my proposals was flawed, and none of the scores reflected the overall impact and scientific merit of any of my proposals. Since the pre-application triage process is completely under-the-table, the 3 reviewers could totally ignore the guidelines of CSR and freely use biased, false, not-fact-based, unfair, unjustified, or even improper comments to systematically bias the scores to the bottom half without concern for any consequences, knowing that their biased comments and scores would never be made public, not even to anyone else in the study section. As an AAW, I have been bullied by the iPSC reviewers in the CSR, who systematically and intentionally biased my hESC research projects to the bottom half, so none of my proposal would be brought up for a full review by the entire panel; purposely used the fake sciences of iPSC and factual errors to discredit hESC research; deliberately forced the grant applicant using the bogus stem cells iPSC even though they were fully aware that iPSC, the genetically-engineered adult cells harboring multiple oncogenes, did not even work; intentionally imposed their own wills and scientific misconducts on the applicant; improperly burdened the applicants with highly controversial and debatable issues that they would not even have open debate themselves; unfairly devalued the applicant’s research because the scientific data were not published in ISSCR’s official journals, such as Stem Cell Report; even threatened the applicant not improve the scores if the bogus stem cells iPSC were not used in the application, including in the entry level grant, such as SBIR Phase I, that does not even have enough money for it [please see samples of NIH summary statements in the attachment]. Such opinion differences regarding iPSC and hESC and their products, regarding the peer-review process of top-scientific journals, ISSCR official journals, and open-access journals are highly controversial and highly debatable issues. Those high-ranking, well-connected, well-paid, and well-funded people would not even allow any open debate about those issues. It is very improper and systemic racist for the reviewers to impose such issues and burdens on an AAW applicant using a under-the-table triage process evading the public eyes; it is unduly unfair and discriminative to intentionally slam an entry level grant application of an AAW to the bottom using such highly controversial issues and highly biased comments they would not even have any open debate in public themselves; it is quite fraudulent and unethical to deliberately block an AAW’s funding for hESC research using such a flawed, under-the-table, behind-closed-doors, pre-application triage process in the CSR and Special Emphasis Panel of the Public Funding Agency of the Federal Government.
The NIH CSR initial peer review system behind-closed-doors has proven to be a fraudulent and discriminative process that disproportionally routes the public funding to those high-ranking, well-connected positions that AAW are excluded from, and has resulted in frauds and wastes of tax-payers’ money in the staggering scale of billions. Such a fraudulent review system behind-closed-doors in the public funding agency is hard to detect, but provides a safe harbor for systemic inequity, and has become an insurmountable and discriminative barrier to AAW who have been marginalized by systemic racism in career advancement, public funding opportunity, and financial assistance they deserve in order to reach their full potential. Such a fraudulent, unaccountable review process in the public funding agency evidently only benefits some high-ranking, well-connected, well-paid, and well-funded positions. As an AAW, I have been systematically denied equal opportunities not only to an entry-level position, such as a tenure-track assistant professor, in order to start my own lab, but also to any entry-level funding, such as SBIR Phase I, in order to found my own company and continue to advance stem cell research. As the woman-founder and Asian American entrepreneur of regenerative medicine start-up, as the world’s top stem cell researcher and innovator, I have been systematically denied equitable access not only to the public funding for stem cell research, but also to the public-funded infrastructure and facility for stem cell research, lab spaces, financial assistance programs and networks. Without ensuring DEI in career advancement, and equitable access and fair competition to the public funding, as a result, the public investment in research has disproportionally gone into high-ranking, well-connected positions, have wasted billions in bogus stem cells like iPSC and MSC, and has missed real opportunities provided by my breakthrough innovations to improve human health and advance the frontiers of medicine.
1.6. Strategies: To Ensure Equal Opportunity and Fair Competition by Abolishing the Fraudulent, Unaccountable, Discriminative, Unilateral Pre-application Triage Process in the Initial Peer Review and Establishing Open, Transparent, Engaged, Bilateral Review System to Monitor and Fix Flawed Reviews and Use Quantitative Metrics-based Review Criteria and Guidelines to Reduce Systemic Barriers
My over 10 years of summary statements of flawed reviews and biased scores have demonstrated that most NIH reviewers in the initial peer review process are incapable of giving a fair review under the closed-door review system. The closed-door initial peer review policies and programs in the CSR of NIH and other public funding agencies have served as insurmountable barriers to equal opportunity, resulting in huge funding gaps and economic disparities between AAW and those high-ranking, well-connected positions that AAW are excluded from. To close the gap, such a fraudulent, unaccountable, discriminative, highly-COI implicated, unilateral pre-application triage process by a few reviewers in the initial peer review of NIH should be abolished. Such a unilateral, unaccountable review process in the CSR gives the reviewers too much power to abuse, deliberately commit frauds, and systematically deny AAW equal opportunity for public funding and financial assistance with flawed reviews, knowing that their discrimination can never be detected under the closed-door review system where systemic racism and COI exist and are unavoidable. It is essential to assess systemic inequality and barriers in a public funding agency, not only for policies, programs, and awards, but also particularly in places hidden from the public, such as the under-the-table pre-application triage process in the initial peer review, where complying with such policies and programs is unchecked and systemic racism is unmonitored. It is also essential to evaluate systemic inequality in NIH funding opportunities, including NIH Common Fund, High Risk High Reward Program, the Brain Initiative, and other RFAs and PARs. For example, on one hand, using the pre-application triage process and flawed review to systemically deny an AAW’s funding for establishing in vivo efficacy of the hESC products in any animal models in order to move into human trials, on the other hand, setting establishing in vivo efficacy in animal models as the extremely high general entry criteria to systematically block an AAW’s equal opportunity for the Blueprint Neurotherapeutics Network for Biologics (BPN-Biologics) (NIH PAR-21-163, PAR-21-233). Although my hESC research projects are transformative, high risk, high reward, and should be funded by NIH Common Fund and High Risk High Reward Program, as an AAW, such funding opportunities have been inaccessible to me for over 10 years, partially because of highly discriminative entry criteria, such as the PI have to be within the 10 years of completing her PhD, while they have systematically blocked my equal opportunity and fair competition for entry of funding for hESC research for over 10 years, including NIH Director’s New Innovator Award Program (RFA-RM-21-016) and Pioneer Award Program (RFA-RM-21-016).
For highly controversial, high risk and high reward, transformative health projects involving hESC research with Ethical, Legal and Social Implications (ELSI) from an AAW, such projects should be given special emphasis and a full panel review should be mandated. Considering the huge funding gap and the big economic disparity that are highly disproportionally to her contributions to the field, using such a fraudulent, unchecked, under-the-table, pre-application triage process evading the public eyes to systematically deny her any full panel reviews and deliberately block her funding for hESC research is racism at its worst. To maintain the integrity, fairness, transparency, and accountability of the grant review and award process of the NIH, an open, transparent, engaged, bilateral review system should be established in the CSR to allow the applicant to present her proposal to the entire study section for a full review and answer the reviewers’ questions and comments. The reviewers should not be allowed to use the later stage evaluation criteria, standard, team, rigor, and outcome, such as R33 and Phase II, to assess the fundability of early stage and entry level grants, such as R21/R61 and Phase I. The reviewers should not be allowed to use highly controversial, highly debatable, irrelevant, or improper issues to burden the applicant. To ensure fair competition and equitable access to the public funding opportunities for AAW, the applicant should be given the opportunity to address reviewers’ comments, biases, and factual errors, and the reviewers should correct the biased scores that do not reflect the overall impact and scientific merit of the proposal immediately after the summary statement is made available. If the applicant addresses the reviewers’ comments, the scores of the resubmission should be significantly improved to reflect the overall impact and scientific merit of the proposal, and the reviewers should not be allowed to raise any more issues in the resubmission to continue to burden the applicant. The applicant should not be forced to agree with the reviewers’ false concepts, biases, and factual errors, and the applicant’s efforts to address such flaws in the summary statement should be valued and used to correct and significantly improve the scores. To ensure accountability and transparency to the public investment in research, and protect the American people and patients’ interests, a public panel and stakeholders should be allowed to also participate in the initial peer review process. An independent, separate from NIH, with a public panel involved, reporting system should be established to monitor the initial peer review process, particularly pre-application triage process if not abolished, for reporting, feedback, quick response, and correction of any flaw, bias, COI, systemic inequality, discrimination, or unfair treatment to AAW to ensure diversity, inclusion, fairness, and integrity of the Federal Funding Agency.
The guidelines of the CSR and the initial peer review system should be assessed for systemic barriers to AAW, and quantitative metrics-based review criteria and guidelines should be established in the CSR to reduce or avoid human errors, biases, COI, and systemic inequality, such as,
· Significance: for stem cell therapy proposal involving a hESC product and advancing human health by addressing an unmet medical need that currently has no solution, the significance should not be scored more than 2 and the proposal should automatically advance to a full panel review;
· Innovation: for PI or company owns patents for the enabling technology used in the proposal, the innovation should not be scored more than 2 and the proposal should automatically advance to a full panel review;
· Approach: for highly likely breakthrough approach that overcomes the major bottleneck, the technical feasibility and scientific merit of the project have been established, and the human cell therapy product prototype has been developed and used in the proposal, the approach should not be scored more than 2 and the proposal should automatically advance to a full panel review;
· Investigator: for PI who has expertise and is highly trained in the proposed research, who is an innovator with inventorship, has a record of highly competitive funding, including K01 award and NIH center grant, to prove her training, and has a track record of publications in area relevant to the proposal to demonstrate that her accomplishments have advanced the field, the investigator should not be scored more than 2 and the proposal should automatically advance to a full panel review;
· Environment: for PI or company located in a university and biotech hub that provides ample opportunities for collaboration, resources, and facility if awarded, the environment should not be scored more than 2 and the proposal should automatically advance to a full panel review.
1.7. Strategies: To Close the Big Gap, Build Human Infrastructure from a Diverse Background, and Improve the Representation Asian-American Women (AAW) at Advanced and Senior Faculty Career Levels and Prestigious Academic Appointments in STEM/Public Health/Health Sciences by Establishing Career Advancement Diversity Award and Outstanding Achievement Diversity Award to Provide Major Funding and Create High-Ranking High-Paying Jobs for Asian American Women
Asian American women are traditionally in low-ranking, low-paying positions that provide no job security, disproportional to their higher educations, skills, achievements, and contributions. When I was a junior faculty, I had to switch 3 institutions even with a NIH K01 award that guaranteed institutional support and career advancement. Over the last decade, my voice has been silenced in the public funding agencies, my view has been suppressed in major agencies and scientific societies, my career advancement has been derailed, my funding opportunities have been blocked by flawed reviews evading the public eyes and, as a low-paying AAW in an inferior position, I was even unfairly banned by ISSCR to present my hESC research breakthroughs. Without a minority voice to support hESC research, without a minority view to provide balance for stem cell research, such systemic inequality gave the bogus stem cells, like iPSC backed and promoted by Bush administration and some high-ranking and high-paying scientists for their own financial gains, the stage to take over the public funding agencies and many major scientific societies by storms. As a result, stem cell research advance has been stalled, and billions of the public investment in stem cell research have been wasted on bogus stem cells, such as iPSC and MSC, over the last decade. To close the big economic gap for AAW, ensure fairness in decision-making processes through the Federal Government, and protect the American people’s interests, not just some high-ranking and well-paid people’s interests, it is crucial to promote AAW to senior and leadership positions that highlight inequality and give some job security in such a highly political, controversial, contentious, and volatile stem cell research field. To build human infrastructure from a diverse background and improve the representation AAW at advanced and senior faculty career levels and prestigious academic appointments in STEM/Public Health/Health Sciences, the Career Advancement Diversity Award and the Outstanding Achievement Diversity Award should be established to provide major funding opportunities and create high-ranking high-paying jobs for qualified and outstanding AAW to advance their career to senior, leadership positions in academia, establish their own labs, and found their own companies. Outstanding AAW should be given the equal opportunity for prestigious academic appointments, such as endowed chair positions and distinguished professor positions that highlight entrenched disparities in universities and research institutes. To ensure equal job opportunity and equal pay, federal-funded big universities and research institutes should be mandated that, for every high-ranking position they offer to a man not from an underrepresented group, they should also offer that same position to a woman from an underrepresented group, like an AAW, if she has similar, or even better qualification criteria, expertise, training, achievement, and highly sought-after skills. Universities and research institutes that have received the Federal government’s infrastructure funding for stem cell research should be mandated to build a human infrastructure for stem cell research from a diverse background so that the public-funded building and facility would not be used for other purposes or left empty, and to offer equal job opportunity to women from underrepresented groups and ensure highly trained AAW to advance their career.
Area 2: Barrier and Burden Reduction:
2.1. To Lower the Insurmountable Entry Barriers, Close the Huge Economic and Funding Gaps, and Reduce the Heavy Burdens for Asian-American Women (AAW) by Using Criteria and Achievement Based Direct Entry Level Funding and Seeding, such as NIH Diversity R01, R21, and SBIR Phase I, to Advance DEI
The lifecycle of NIH grants submission and review is very long, and it usually takes 9-12 months. Majority of proposals are not funded in the first submission. It usually takes about 2 years if there is a resubmission. In addition, AAW are overburdened with flawed reviews and systemic inequality in the NIH initial peer review system that have undermined the bedrock of American democracy and tarnished the image of the Federal Funding Agencies. To lower the insurmountable entry barriers, close the huge economic and funding gaps, and reduce the heavy burdens for AAW, direct entry level funding, such as NIH Diversity R01 and R21, and direct seeding, such as SBIR Phase I, should be established to speed up the funding process by using criteria- and achievement-based evaluation, such as,
· Significance: Does it address an unmet medical need that currently has no solution?
· Innovation: Does the PI or company hold the patent for the enabling technology used in the proposal? Is the technology a breakthrough innovation?
· Approach: Does the approach overcome a major bottleneck in the field? Is hESC product developed and used in the proposal? Is it a proposal for RMAT, if success, will it save life or dramatically improve quality of life?
· Investigator: Is the PI an AAW? Does she have inventorship and a proven record of training and publication in relevant field?
· Environment: Is the PI or company located in a hub of university and biotech that offers ample opportunities for her if funded?
2.2. To Close the Funding Gaps and Advance DEI by Setting Aside 5% Fund of Every Major Funding Opportunity and Infrastructure Award, and Mandating Matching Award for Asian-American Women (AAW) to Ensure that the Best Science Gets Funded
To close the big economic disparities and funding gaps and advance equity, the Federal funding agencies should be mandated to set aside 5% of every major funding opportunity, including NIH Common Fund, High Risk High Reward Program, the Brain Initiative, the Blueprint Network (BPN), and Infrastructure Award, for AAW. For every grant they review and award to a high-ranking man not from an underrepresented group, NIH should also review and award the equitable matching funding to a woman from an underrepresented group, like an AAW, if her proposal equivalently or even better addresses the same problem or unmet medical challenge, to ensure that the best science gets funded. For every infrastructure award to a major university or research institute for stem cell research, the Federal funding agencies should also award the equitable matching fund to an AAW-owned/founded small business or research institute, if her institute or small business conducts breakthrough stem cell research; holds patents and exclusive rights to life-saving, transformative health projects; has hESC products developed to advance human health; deserving and in more urgent need of such infrastructure and facility fund for transformative health projects; and better serves the American people and patients’ interests.
2.3. Form Special Emphasis Panels Specifically for Controversial, High Risk High Reward Health Projects Involving hESC Research and Establish Regulatory Policies Specifically Addressing hESC Products for RMAT Involving Ethical Issues
The hESC research is enormously important to NIH’s mission, and provides the unique model systems to seek fundamental knowledge about humans and many diseases, including cancers and brain tumors, and the application of that knowledge to enhance human health, lengthen life, and reduce illness and disability. It holds huge promise for treating major human diseases that have been challenging to traditional medicine, and is the foundation of cutting-edge, transformative health projects, the new frontiers of regenerative medicine, critical to US’s leadership position in biomedical research in the world. Millions of people are pinning their hopes on hESC research. To accelerate patients’ access to new therapy and save life, it is critical to establish separate special emphasis review panels, funding programs, and fast-track funding specifically for highly transformative health projects involving hESC products, and form regulatory policies specifically addressing hESC products for RMAT involving ethical issues, not to be mixed with genetically engineered cells like iPSC and leads generated from fly, zebrafish, and animals. The hESC are natural-originated, unmodified human cells, like bone marrow stem cells (BMSC) and MSC; but the iPSC product is a genetically-engineered product harboring multiple oncogenes, which creates another, totally different level of FDA regulation. So far, no genetically-engineered product even harboring one oncogene is ever allowed by FDA. However, over the last decade, those high-ranking, well-connected iPSC people, including the Dean of Harvard Medical School and the presidents and vice presidents of ISSCR, have been using their positions and influences to promote the deceptive identical theory to blear the line between the bogus stem cells iPSC (the genetically-engineered adult cell harboring oncogenes) and the hESC (the human embryo-derived cells), to evade the FDA regulation for genetically-engineered cells, and to take advantage of FDA RMAT designation created by hESC research breakthroughs, but NOT iPSC, for their own financial gains. In addition, many NIH grants review criteria and FDA regulation are set for leads generated from fly, zebrafish, and animals, such as establishing in vivo efficacy in animal models, which is a necessary step for leads generated from studies not in humans before going to human trials. However, hESC are derived from human embryos; their efficacy to differentiate into a wide range of human cells in need of repair is intrinsic to hESC and pre-set; going back to test in animal models is like bending backwards; in vitro efficacy and 3D data should be sufficient. To accelerate the development of new treatments, cures, and therapies for many life-threatening and devastating diseases and injuries, and speed up the process of entering into human trials, the hESC health projects should not be subject to the same harsh review criteria, high entry standards, and regulation equivalent to fly, zebrafish, animals, and any genetically-engineered cells. We know MSC are not effective, particularly for neurological and heart diseases. No one has established any in vivo efficacy in any animal models for MSC, not even any in vitro efficacy. But MSC is allowed to go straight to humans, which results in many bogus stem cell clinics out there. The hESC are the same natural-originated, unmodified human cells, like BMSC and MSC. The difference is that hESC products are effective, with convincing data of in vitro efficacy and even in vivo efficacy data in certain animal models [e.g., Liu YW, et al. HESC-derived cardiomyocytes restore function in infarcted hearts of non-human primates. Nat Biotechnol. 2018;36(7):597-605. doi: 10.1038/nbt.4162; Kriks S, et al. Dopamine neurons derived from hESC efficiently engraft in animal models of Parkinson’s disease. Nature 2011;480:547–51]. The safe and effective hESC products should not receive the harsh NIH grants review criteria, long lifecycle of NIH grants submission, and FDA regulation for leads generated from fly, zebrafish, animals, and genetically engineered cells. New NIH special emphasis review criteria/panels and FDA regulations should be established specifically for hESC products to ensure faster applications for transformative health projects involving hESC research.
Area 3: Procurement and Contracting:
Mandate Set-Aside 5% Infrastructure Fund to Seed and Support the Asian-American Woman-Owned/Founded Small Business of High Priority to the Nation’s Well-Being and Improving Human Health through Procurement and Contracting to Advance DEI
The hESC research is of high priority to the Nation’s well-being, improving human health, advancing medicine, even national defense, and the Nation’s lead position in the frontiers of science and technology. There are big gaps in resources, facilities, and infrastructure between AAW-owned small businesses and big universities. Woman-owned/founded small businesses often struggle with limited resources and lack of facility, particularly for stem cell research institute and regenerative medicine startup, while hundreds of millions of public funding have gone to infrastructures in large universities that are inaccessible to woman-owned/founded small businesses. Such systemic inequality has become one of the major reasons for an AAW-founder, though the world’s top stem cell researcher and innovator, unable to continue to advance hESC research. To create jobs and increase productivity, reduce barriers for AAW to enter into the work force and contribute their highly sought-after expertise, training, and skills to the Nation, and speed up the funding process and build infrastructure for new treatments, cures, and therapies in urgent need for many life-threatening and devastating diseases, the congress should mandate set-aside 5% infrastructure fund to seed and support AAW-owned/founded small business of high priority to the Nation’s well-being and improving human health through direct procurement and contracting to advance DEI. For AAW-owned minority research institute or startup conducting breakthrough hESC research and holding patents and exclusive rights for life-saving, transformative health projects, such direct procurement and contracting mechanisms ensure the Nation to build a competent stem cell research and regenerative medicine facility and human infrastructure capable of advancing cutting-edge, transformative health projects to best serve the American people and patients’ interests.
Area 4: Financial Assistance:
To Allocate Financial Assistance and Set up the Diversity Service Award to Outstanding Asian-American Women (AAW) Who Have Made Breakthrough Innovations to Advance Stem Cell Therapy with the Transformative Health Projects for many Americans Suffering from Life-Threatening and Devastating Diseases, but Have Been Blocked any Funding Opportunities by Systemic Inequality
Women, particularly Asian women, face enormous systemic inequities to advance their career in academia, to get recognized for what they have achieved, and to get promoted to a prominent and leadership position traditionally held by men. My experiences have told me that it is really hard for AAW to advance our career to senior levels, to leadership positions, even though we have done extraordinary things, even though we have gained leadership vision and expertise, even though we have achieved what most people couldn’t achieve. There are big economic disparities for AAW founders who have been systematically denied career advancement to high-paying jobs and entry-level funding opportunities, even living in persistent poverty, highly disproportional to their higher educations, skills, achievements, and contributions. As the woman-founder and Asian American entrepreneur of regenerative medicine start-up, as the world’s top stem cell researcher and innovator, I represent a prominent figure and a strong voice to advocate public funding to advance hESC research and public support to improve policy making on a global stage that also serve to promote DEI; to gain equitable access and recognition for AAW in a field dominated by men; to improve the representation of women at advanced and senior faculty career levels in STEM/Public Health/Health Sciences; to dismantle barriers to executive leadership roles historically excluded from women; and to improve leadership prospects for women in STEM fields. My long service activities to promote DEI, including breakthrough innovations in the emerging technology of regenerative medicine and leadership in stem cell research, have contributed to improving policy making for hESC research in the Federal Government, including the more relaxed NIH funding policy for hESC research and the FDA RMAT Designation Program, and have also opened up scores of funding opportunities, including the White House BRAIN Initiative, the NIH Common Fund, the NIH High-Risk High-Reward Program, and the DOD ATB-MII Initiative. However, systemic inequality has blocked me any funding opportunities opened up by my breakthrough innovations in hESC research. I often have to work full-time without pay. To add insult to injury, our mortgage companies, first Ocwen and then SLS, even gave us a hard time to seek financial assistance from HAMP programs and tried to foreclose our house multiple times. The congress should allocate financial assistance and set up the Diversity Service Award to outstanding AAW who have made such sacrifices to the Nation’s interests and priority in order to advance stem cell therapy with the transformative health projects for many Americans suffering from life-threatening and devastating diseases; to lift them from persistent poverty disproportional to their higher educations, skills, achievements, and contributions; and to even their pay-scales to those high-ranking, well-paid, well-funded positions that they are excluded from.
Area 5: Stakeholder and Community Engagement:
To Ensure Fairness in Decision-Making, Protect the American People’s Interests, and Maintain a High Return of the Public Investment in Research, it is Crucial for Major Agencies, including NIH, FDA, HHS, to Include a Minority Voice and Have a Minority View
The voices of minority are often suppressed or silenced in major agencies and societies that are mostly controlled and influenced by high-ranking and well-connected positions, even though those people of high power would back and promote frauds and wastes for their own financial gains. The lack of DEI is one of the major reasons that such an apparently flawed concept of iPSC and such bogus stem cells iPSC could dominate the public funding agencies and major scientific societies for over 10 years and waste billions of taxpayer money. Over the last decade, the hESC research labs inside and outside NIH have been replaced by the bogus iPSC labs, the NIH-funded hESC centers have been replaced by the bogus iPSC centers, the progress of stem cell research has been stalled, and tax-payers’ money has wasted billions on bogus stem cells. To ensure fairness in decision-making through the Federal Government, protect the American people’s interests, and maintain a high return of the public investment in research, it is crucial for major agencies, including NIH, FDA, HHS, to include a minority voice and have a minority view. It should be mandated that the NIH review panels, the committee boards, the scientific advisory boards, the policy boards, the FDA advisory boards, and other committees, panels, and boards of those agencies and major scientific societies should include at least one AAW on board to ensure their voices be heard, their visions be seen, their skills be employed, and their advices be valued.