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Originally posted by johnkarls » Tue Jan 31, 2017 1:14 pm
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http://www.cell.com/cell/abstract/S0092-8674(16)31752-4
Cell – Volume 168, Issue 3, pp. 473-486, 16 January 2017
Interspecies Chimerism with Mammalian Pluripotent Stem Cells
Jun Wu, Aida Platero-Luengo, Masahiro Sakurai, Atsushi Sugawara, Maria Antonia Gil, Takayoshi Yamauchi, Keiichiro Suzuki, Yanina Soledad Bogliotti, Cristina Cuello, Mariana Morales Valencia, Daiji Okumura (Footnote 7), Jingping Luo, Marcela Vilariño, Inmaculada Parrilla, Delia Alba Soto, Cristina A. Martinez, Tomoaki Hishida, Sonia Sánchez-Bautista, M. Llanos Martinez-Martinez, Huili Wang, Alicia Nohalez, Emi Aizawa, Paloma Martinez-Redondo, Alejandro Ocampo, Pradeep Reddy, Jordi Roca, Elizabeth A. Maga, Concepcion Rodriguez Esteban, W. Travis Berggren, Estrella Nuñez Delicado, Jeronimo Lajara, Isabel Guillen, Pedro Guillen, Josep M. Campistol, Emilio A. Martinez, Pablo Juan Ross, Juan Carlos Izpisua Belmonte (Footnote 8 ).
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Footnote 7: Present address: Graduate School of Agriculture, Department of Advanced Bioscience, Kinki University, 3327-204 Nakamachi, Nara 631-8505, Japan
Footnote 8: Lead Contact
Summary
Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.
Summary
Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.
Introduction
Embryonic pluripotency has been captured in vitro at a spectrum of different states, ranging from the naive state, which reflects unbiased developmental potential, to the primed state, in which cells are poised for lineage differentiation (Weinberger et al., 2016, Wu and Izpisua Belmonte, 2016). When attempting to introduce cultured pluripotent stem cells (PSCs) into a developing embryo of the same species, recent studies demonstrated that matching developmental timing is critical for successful chimera formation. For example, naive mouse embryonic stem cells (mESCs) contribute to chimera formation when injected into a blastocyst, whereas primed mouse epiblast stem cells (mEpiSCs) efficiently engraft into mouse gastrula-stage embryos, but not vice versa (Huang et al., 2012, Wu et al., 2015). Live rodent interspecies chimeras have also been generated using naive PSCs (Isotani et al., 2011, Kobayashi et al., 2010, Xiang et al., 2008). However, it remains unclear whether naive PSCs can be used to generate chimeras between more distantly related species.
The successful derivation of human PSCs (hPSCs), including ESCs from pre-implantation human embryos (Reubinoff et al., 2000, Thomson et al., 1998), as well as the generation of induced pluripotent stem cells (iPSCs) from somatic cells through cellular reprograming (Takahashi et al., 2007, Park et al., 2008, Wernig et al., 2007, Yu et al., 2007, Aasen et al., 2008), has revolutionized the way we study human development and is heralding a new age of regenerative medicine. Several lines of evidence indicate that conventional hPSCs are in the primed pluripotent state, similar to mEpiSCs (Tesar et al., 2007, Wu et al., 2015). A number of recent studies have also reported the generation of putative naive hPSCs that molecularly resemble mESCs (Gafni et al., 2013, Takashima et al., 2014, Theunissen et al., 2014). These naive hPSCs have already provided practical and experimental advantages, including high single-cell cloning efficiency and facile genome editing (Gafni et al., 2013). Despite these advances, it remains unclear how the putative higher developmental potential of naive hPSCs can be used to better understand human embryogenesis and to develop regenerative therapies for treating patients.
Like naive rodent PSCs, naive hPSCs can potentially be used to generate interspecies chimeras for studying human development and disease, and producing functional human tissues via interspecies blastocyst complementation. To date, however, all reported attempts on generating hPSC-derived interspecies chimeras have used the mouse as the host animal, and the results obtained suggest that this process is rather inefficient (Gafni et al., 2013, Theunissen et al., 2014, Theunissen et al., 2016). Although the mouse is one of the most important experimental models for stem cell research, there are considerable differences between humans and mice (e.g., early post-implantation development, embryo size, gestational length, and developmental speed), which may hinder not only the efficiency but also the usefulness of human-mouse chimeric studies. Thus, expanding the repertoire of host species may complement this incipient but promising area of research in the field of regenerative medicine. In particular, interspecies chimera research of hPSCs using ungulates, e.g., pigs, cattle, and sheep, could lead to improved research models, as well as novel in vivo strategies for (1) generating human organs and tissues, (2) designing new drug screening methodologies, and (3) developing new human disease models (Wu and Izpisua Belmonte, 2015). Experiments to empirically test and evaluate the chimeric contribution of various types of hPSCs in the ungulates are thus imperative, but currently lacking. To start filling this void, we tested different types of hPSCs for their chimeric contribution potential in two ungulate species, pigs and cattle.
Results
Naive Rat PSCs Robustly Contribute to Rat-Mouse Interspecies Chimera Formation
We first used rodent models to gain a better understanding of the factors and caveats underlying interspecies chimerism with PSCs. To this end, we used two chimeric-competent rat ESC lines, DAC2 and DAC8 (Li et al., 2008). We labeled both lines with a fluorescent marker, humanized kusabira orange (hKO), for cell tracking and injected them into mouse blastocysts. Following embryo transfer (ET) into surrogate mouse mothers, both DAC2 and DAC8 lines gave rise to live rat-mouse chimeras (Figures 1A and S1A). Many of the chimeras developed into adulthood, and one chimera reached 2 years of age (Figure 1A), indicating that the xenogeneic rat cells sustained the physiological requirements of the mouse host without compromising its life span. We also generated two rat iPSC lines (SDFE and SDFF) from tail tip fibroblasts (TTFs) isolated from a neonatal Sprague-Dawley rat and used them to generate rat-mouse chimeras. Similar to rat ESCs, rat iPSCs could also robustly contribute to chimera formation in mice (Figure S1B). Overall, the chimera forming efficiencies of all rat PSC lines tested were ∼20%, consistent with a previous report (Figure 1B) (Kobayashi et al., 2010).
We observed contribution of rat cells to a wide range of tissues and organs in both neonatal and aged rat-mouse chimeras (Figures 1C, S1A, and S1B). We examined aging-related histone marks in both neonatal and aged chimeras and found that the 2-year-old chimera exhibited histone signatures characteristic of aging (Figure 1D). We quantified the degree of chimerism in different organs of the aged chimera via quantitative qPCR analysis of genomic DNA using a rat-specific primer (Table S2). We found that different tissues contained different percentages of rat cells, with the highest contribution observed in the heart (∼10%) (Figure 1E).
One anatomical difference between mice and rats is that rats lack a gallbladder. In agreement with a previous report (Kobayashi et al., 2010), we also observed the presence of gallbladders in rat-mouse chimeras (chimeras derived from injecting rat PSCs into a mouse blastocyst). Interestingly, rat cells contributed to the chimeric gallbladder and expressed the gallbladder epithelium marker EpCAM (Figures 1F and S1C), which suggests that the mouse embryonic microenvironment was able to unlock a gallbladder developmental program in rat PSCs that is normally suppressed during rat development.
A Versatile CRISPR-Cas9-Mediated Interspecies Blastocyst Complementation System
Chimeric contribution of PSCs is random and varies among different host blastocysts and donor cell lines used. To selectively enrich chimerism in a specific organ, a strategy called blastocyst complementation has been developed where the host blastocysts are obtained from a mutant mouse strain in which a gene critical for the development of a particular lineage is disabled (Chen et al., 1993, Kobayashi et al., 2010, Wu and Izpisua Belmonte, 2015). Mutant blastocysts used for complementation experiments were previously obtained from existing lines of knockout mice, which were generated by gene targeting in germ-line-competent mouse ESCs—a time-consuming process. To relieve the dependence on existing mutant strains, we developed a blastocyst complementation platform based on targeted genome editing in zygotes. We chose to use the CRISPR-Cas9 system, which has been harnessed for the efficient generation of knockout mouse models (Wang et al., 2013) (Figure 2A).
For proof-of-concept, we knocked out the Pdx1 gene in mouse by co-injecting Cas9 mRNA and Pdx1 single-guide RNA (sgRNA) into mouse zygotes. During mouse development, Pdx1 expression is restricted to the developing pancreatic anlagen and is a key player in pancreatic development. Mice homozygous for a targeted mutation in Pdx1 lack a pancreas and die within a few days after birth (Jonsson et al., 1994, Offield et al., 1996). Similarly, Pdx1−/− mice generated by the zygotic co-injection of Cas9 mRNA and Pdx1 sgRNA were apancreatic, whereas other internal organs appeared normal (Figure S2A). These mice survived only a few days after birth. We observed the efficiency for obtaining Pdx1−/− mouse via CRISPR-Cas9 zygote genome editing was ∼60% (Figure S2F). Next, we combined zygotic co-injection of Cas9/sgRNA with blastocyst injection of rat PSCs, and found that rat PSC-derivatives were enriched in the neonatal pancreas of Pdx1−/− mice and expressed α-AMYLAYSE, a pancreatic enzyme that helps digest carbohydrates (Figures 2B and S2B). Of note is that in these animals the pancreatic endothelial cells were still mostly of mouse origin, as revealed by staining with an anti-CD31 antibody (Figure 2B). Importantly, pancreas enriched with rat cells supported the successful development of Pdx1−/− mouse host into adulthood (>7 months), and maintained normal serum glucose levels in response to glucose loading, as determined using the glucose tolerance test (GTT) (Figure S2C).
Taking advantage of the flexibility of the CRISPR-Cas9 zygotic genome editing, we next sought to enrich xenogenic rat cells toward other lineages. Nkx2.5 plays a critical role in early stages of cardiogenesis, and its deficiency leads to severe growth retardation with abnormal cardiac looping morphogenesis, an important process that leads to chamber and valve formation (Lyons et al., 1995, Tanaka et al., 1999). Mice lacking Nkx2.5 typically die around E10.5 (Lyons et al., 1995, Tanaka et al., 1999). Consistent with previous observations, CRISPR-Cas9 mediated inactivation of Nkx2.5 resulted in marked growth-retardation and severe malformation of the heart at E10.5 (Figure S2D). In contrast, when complemented with rat PSCs, the resultant Nkx2.5−/− mouse hearts were enriched with rat cells and displayed a normal morphology, and the embryo size was restored to normal (Figures 2C and S2D). Of note is that although rat PSCs rescued embryo growth and cardiac formation in E10.5 Nkx2.5−/− mouse embryos, to date we still have not obtained a live rescued chimera (n = 12, where n is the number of ETs). Pax6 is a transcription factor that plays key roles in development of the eye, nose and brain. Mice homozygous for a Pax6 loss-of-function mutation lack eyes, nasal cavities, and olfactory bulbs, and exhibit abnormal cortical plate formation, among other phenotypes (Gehring and Ikeo, 1999). Pax6 is best known for its conserved function in eye development across all species examined (Gehring and Ikeo, 1999). In agreement with the published work, CRISPR-Cas9 mediated Pax6 inactivation disrupted eye formation in the E15.5 mouse embryo (Figure S2E). When complemented with rat PSCs, we observed the formation of chimeric eyes enriched with rat cells in Pax6−/− mouse neonate (Figures 2D and S2E). Similar to Pdx1−/−, we observed efficient generation of homozygous Nkx2.5−/− and Pax6−/− mouse embryos via zygotic co-injection of Cas9 mRNA and sgRNAs (Figure S2F). All DNA sequencing results of CRISPR-Cas9 mediated gene knockouts and gRNA sequences are summarized in Tables S1 and S2, respectively.
In sum, for the pancreas, heart, and eye, as well as several other organs (data not shown), we successfully generated chimerized organs that were enriched with rat cells, demonstrating the efficacy and versatility of the CRISPR-Cas9 mediated interspecies blastocyst complementation platform.
Naive Rodent PSCs Do Not Contribute to Chimera Formation in Pigs
It is commonly accepted that the key functional feature of naive PSCs is their ability to generate intraspecies germline chimeras (Nichols and Smith, 2009). Studies in rodents also support the notion that attaining the naive pluripotent state is the key step in enabling chimera formation across species boundaries (Xiang et al., 2008, Isotani et al., 2011, Kobayashi et al., 2010). However, it has not yet been tested whether naive rodent PSCs can contribute to chimera formation when using a non-rodent host. To further examine the relationship between naive PSCs and interspecies chimerism, we injected rat ESCs into pig blastocysts followed by ET to recipient sows. In addition to rat ESCs, we also used a germline competent mouse iPSC line (Okita et al., 2007). Several criteria were used to determine the chimeric contribution of rodent cells in pig embryos, namely, (1) detection of fluorescence (hKO) signal, (2) immunohistochemical (IHC) labeling of embryo sections with an anti-hKO antibody, and (3) genomic PCR with mouse- or rat-specific primers targeting mitochondrial DNA (mtDNA) (Figure 3A). We terminated the pregnancy between day 21–28 of pig development and collected embryos derived from the injection of mouse iPSCs or rat ESCs into pig blastocyst (26 and 19 embryos, respectively) (Figure 3B; Table S3). We failed to detect any hKO signal in both normal size and growth retarded embryos (Figure 3B). We next sectioned the pig embryos and stained them with an antibody against hKO. Similarly, we did not detect any hKO-positive cells in the embryonic sections examined (data not shown). Finally, we employed a more sensitive test, using genomic PCR to amplify rat- or mouse-specific mtDNA sequences (pig-specific mtDNA primers served as the loading control) (Table S2). Consistently, genomic PCR analyses did not detect any rodent contribution to the pig embryos (Figure 3C). Taken together, although naive rodent PSCs can robustly contribute to rodent-specific interspecies chimeras, our results show that these cells are incapable of contributing to normal embryonic development in pigs.
Generation of Naive, Intermediate, and Primed hiPSCs
Next, we sought to systematically evaluate the chimeric competency of hPSCs in ungulate embryos. We generated hiPSCs using several reported naive PSC culture methods, a culture protocol supporting a putative intermediate pluripotent state between naive mESCs and primed mEpiSCs (Tsukiyama and Ohinata, 2014), and a primed culture condition (Figure 4A). Mouse ground state culture condition (2iL) induces the differentiation of primed hPSCs. However, when combined with the forced expression of NANOG and KLF2 (NK2), transcription factors that help to maintain murine naive pluripotency, 2iL culture can stabilize hPSCs in an immature state (Takashima et al., 2014, Theunissen et al., 2014). We generated doxycycline (DOX)-inducible NK2-expressing naive hiPSCs cultured in 2iL medium from primed hiPSCs (2iLD-hiPSCs). Transgene-free primed hiPSCs were reprogramed from human foreskin fibroblasts (HFFs) using episomal vectors (Okita et al., 2011). For comparison, we also generated naive hiPSCs from HFFs using the NHSM culture condition (Gafni et al., 2013) (NHSM-hiPSCs). It has been shown that cells grown in 4i medium, a simplified version of NHSM, have a significant potential for germ cell induction, a distinguishing feature between naive mESCs and primed mEpiSCs (Irie et al., 2015). Thus, we also culture-adapted NHSM-hiPSCs in 4i medium (4i-hiPSCs), resulting in stable 4i-hiPSCs with similar morphological and molecular characteristics to parental NHSM-hiPSCs (Figure 4B). In addition, we generated another type of hiPSC by direct reprogramming of HFFs in a modified mEpiSC medium containing bFGF, Activin-A, and CHIR99021 (FAC; Figure 4A). mEpiSCs cultured in FAC medium exhibited features characteristic of both naive mESCs and primed mEpiSCs, supporting an intermediate pluripotent state (Tsukiyama and Ohinata, 2014). hiPSCs generated and cultured in FAC medium (FAC-hiPSCs) displayed a colony morphology intermediate between that of 2iLD- and primed hiPSCs, with less defined borders (Figure 4B). 2iLD-hiPSCs, NHSM-hiPSCs, 4i-hiPSCs, and FAC-hiPSCs could all be stably maintained long term in culture, preserving normal karyotypes and the homogeneous, nuclear localization of OCT4 protein (Figure 4B; data not shown). Notably, similar to hiPSCs grown in naive cultures (2iLD-hiPSCs, NHSM-hiPSCs, 4i-hiPSCs), FAC-hiPSCs could also be efficiently propagated by single-cell dissociation without using a ROCK kinase inhibitor. After injecting cells into the kidney capsule of immunodeficient NSG mice, all of these hiPSCs formed teratomas that consisted of tissues from all three germ layers: endoderm, mesoderm, and ectoderm (Figure S3A). To facilitate the identification of human cells in subsequent chimera experiments, we labeled hiPSCs with either green fluorescence protein (GFP) or hKO fluorescence markers.
Chimeric Contribution of hiPSCs to Pig and Cattle Blastocysts
The ability to integrate into the inner cell mass (ICM) of a blastocyst is informative for evaluating whether hiPSCs are compatible with pre-implantation epiblasts of the ungulate species. This is also one of the earliest indicators of chimeric capability. We therefore evaluated interspecies chimeric ICM formation by injecting hiPSCs into blastocysts from two ungulate species, pig and cattle.
Cattle-assisted reproductive technologies, such as in vitro embryo production, are well established given the commercial benefits of improving the genetics of these animals. Cattle also serve as a research model because of several similarities to human pre-implantation development (Hansen, 2014, Hasler, 2014). Using techniques for producing cattle embryos in vitro, we developed a system for testing the ability and efficiency of hiPSCs to survive in the blastocyst environment and to integrate into the cattle ICM (Figure 4C). Cattle embryos were obtained by in vitro fertilization (IVF) using in vitro matured oocytes collected from ovaries obtained from a local slaughterhouse. The tightly connected cells of the blastocyst trophectoderm from large livestock species, such as pig and cattle, form a barrier that complicates cell microinjection into the blastocoel. Thus, microinjection often results in embryo collapse and the inability to deposit the cells into the embryo. To facilitate cell injection we employed a laser-assisted approach, using the laser to perforate the zona pellucida and to induce damage to a limited number of trophectoderm cells. This allowed for easy access into the blastocyst cavity for transferring the human cells (Figure S3B). Furthermore, the zona ablation and trophectoderm access allowed use a blunt-end pipette for cell transfer, thus minimizing further embryo damage. This method resulted in a nearly 100% injection effectiveness and >90% embryo survival.
To determine whether hiPSCs could engraft into the cattle ICM, we injected ten cells from each condition into cattle blastocysts collected 7 days after fertilization. After injection, we cultured these blastocysts for additional 2 days before analysis. We used several criteria to evaluate the chimeric contribution of hiPSCs to cattle blastocysts: (1) average number of human cells in each blastocyst, (2) average number of human cells in each ICM, (3) percentage of blastocysts with the presence of human cells in the ICM, (4) percentage of SOX2+ human cells in the ICM, and (5) percentage of human cells in the ICM that are SOX2+ (Figure 4C). Our results indicated that both naive and intermediate (but not primed) hiPSCs could survive and integrate into cattle ICMs, albeit with variable efficiencies (Figures 4D and S3C–S3E; Table S4). Compared with other cell types, 4i-hiPSCs exhibited the best survival (22/23 blastocysts contained human cells), but the majority of these cells lost SOX2 expression (only 13.6% of human cells remained SOX2+). On average, 3.64 4i-hiPSCs were incorporated into the ICM. NHSM-hiPSCs were detected in 46 of 59 injected blastocysts, with 14.41 cells per ICM. Of these, 89.7% remained SOX2+. For 2iLD-hiPSCs, 40 of 52 injected blastocysts contained human cells, with 5.11 cells per ICM, and 69.9% of the ICM-incorporated human cells remained SOX2+. FAC-hiPSCs exhibited moderate survival rate (65/101) and ICM incorporation efficiency (39/101), with an average of 2.31 cells incorporated into the ICM, and 89.3% remaining SOX2+.
We also performed ICM incorporation assays by injecting hiPSCs into pig blastocysts. Because certain complications are frequently associated with pig IVF (Abeydeera, 2002, Grupen, 2014) (e.g., high levels of polyspermic fertilization), we used a parthenogenetic activation model, which enabled us to efficiently produce embryos that developed into blastocysts (King et al., 2002). Pig oocytes were obtained from ovaries collected at a local slaughterhouse. Once the oocytes were matured in vitro, we removed the cumulus cells and artificially activated the oocytes using electrical stimulation. They were then cultured to blastocyst stage (Figure 4C). We injected ten hiPSCs into each pig parthenogenetic blastocyst and evaluated their chimeric contribution after 2 days of in vitro culture (Figures 4C and S3C–S3E; Table S4). Similar to the results in cattle, we found that hiPSCs cultured in 4i and NHSM media survived better and yielded a higher percentage of blastocysts harboring human cells (28/35 and 37/44, respectively). Also, among all blastocysts containing human cells, we observed an average of 9.5 cells per blastocyst for 4i-hiPSCs and 9.97 cells for NHSM-hiPSCs. For NHSM-hiPSCs, 19/44 blastocysts had human cells incorporated into the ICM. In contrast, only 6/35 blastocysts had 4i-hiPSCs localized to the ICM. For 2iLD-hiPSCs, we observed an average of 5.7 cells per blastocyst, with 2.25 human cells localized to the ICM. For FAC-hiPSCs, an average of 3.96 and 1.62 human cells were found in the blastocyst and ICM, respectively. Once incorporated into the ICM, 82.2%, 72%, 60.9%, and 40% of 2iLD-, 4i-, NHSM-, and FAC-hiPSCs, respectively, stained positive for the pluripotency marker SOX2. These results indicate that both naive and intermediate hiPSCs seem to perform better when injected into cattle than pig blastocysts. This suggests a different in vivo blastocyst environment in pig and cattle, with the cattle blastocysts providing an environment that is more permissive for hiPSC integration and survival.
Chimeric Contribution of hiPSCs to Post-implantation Pig Embryos
Although ICM incorporation of hiPSCs is the necessary first step to contribute to the embryo proper of host animals, it has limited predictive value for post-implantation chimera formation, as other factors are involved. Next, we investigated if any of the naive and intermediate hiPSCs that we generated, which showed robust ICM incorporation in pre-implantation blastocysts, could contribute to post-implantation development following ET. The pig has certain advantages over cattle for experiments involving post-implantation embryos, as they are a polytocus species, and are commonly used as a translational model given their similarities to humans concerning organ physiology, size, and anatomy. We thus chose the pig for these experiments. Since there was little to no contribution of primed hiPSCs, even at the pre-implantation blastocyst stage, we excluded these cells from the ET experiments. Pig embryos were derived in vivo or through parthenogenesis. A total of 167 embryo donors were used in this study, from which we collected 1,298 zygotes, 1,004 two-cell embryos and 91 morulae (Table S5). Embryos were cultured in vitro until they reached the blastocyst stage (Figures S4AA and S4B). Overall, 2,181 good quality blastocysts with a well-defined ICM were selected for subsequent blastocyst injections, of which 1,052 were derived from zygotes, 897 from two-cell embryos, 91 from morulae, and 141 from parthenogenetic activation (Table S5). We injected 3-10 hiPSCs into the blastocoel of each of these blastocysts (Figures 5A, S4A, and S4C; Table S6). After in vitro embryo culture, a total of 2,075 embryos (1,466 for hiPSCs; Table S6; 477 for rodent PSCs; Table S3) that retained good quality were transferred to surrogate sows. A total of 41 surrogate sows received 30–50 embryos each, resulting in 18 pregnancies (Table S6). Collection of embryos between day 21-28 of development resulted in the harvesting of 186 embryos: 43 from 2iLD-hiPSCs, 64 from FAC-hiPSCs, 39 from 4i-hiPSCs, and 40 from NHSM-hiPSCs (Figures 5B, S4A, S4D, and S4F). In addition, 17 control embryos were collected from an artificially inseminated sow (Figure 5B).
Following evaluating the developmental status of the obtained embryos, more than half showed retarded growth and were smaller than control embryos (Figures 5B and S4B), as was seen when pig blastocysts were injected with rodent PSCs (Figure 3B). Among different hiPSCs, embryos injected with FAC-hiPSCs were more frequently found to be normal size (Figure 5C). From the recovered embryos, and based on fluorescence imaging (GFP for 2iLD-hiPSCs and FAC-hiPSCs; hKO for 4i-hiPSCs and NHSM-hiPSCs), we observed positive fluorescence signal (FO+) in 67 embryos among which 17 showed a normal size and morphology, whereas the rest were morphologically underdeveloped (Figures 5B). In contrast, among fluorescence negative embryos we found the majority (82/119) appeared normal size (Figure 5E), suggesting contribution of hiPSCs might have interfered with normal pig development. Closer examination of the underdeveloped embryos revealed that 50 out of 87 were FO+ (Figures 5B). Among all the FO+ embryos the distribution of normal size versus growth retarded embryos for each cell lines was: 3:19 for 2iLD-hiPSCs, 7:14 for FAC-hiPSCs, 2:12 for 4i-hiPSCs, and 5:5 for NHSM-hiPSCs (Figure 5D). Among normal size embryos we found 3/13 from 2iLD-hiPSCs, 7/47 from FAC-hiPSCs, 2/14 from 4i-hiPSCs, and 5/25 from NHSM-hiPSCs that were FO+ (Figure 5B). All normal size FO+ embryos derived from 2iLD-hiPSCs, 4i-hiPSCs, or NHSM-hiPSCs showed a very limited fluorescence signal (Figure S5A). In contrast, normal size FO+ FAC-hiPSC-derived embryos typically exhibited a more robust fluorescence signal (Figures 6A and S5A).
Detecting fluorescence signal alone is insufficient to claim chimeric contribution of donor hiPSCs to these embryos, as auto-fluorescence from certain tissues and apoptotic cells can yield false positives, especially when chimerism is low. We thus sectioned all normal size embryos deemed positive based on the presence of fluorescence signal and subjected them to IHC analyses with antibodies detecting GFP or hKO. For 2iLD-hiPSC-, 4i-hiPSC-, and NHSM-hiPSC-derived embryos, in agreement with fluorescence signals observed in whole-embryo analysis, we detected only a few hKO- or GFP-positive cells in limited number of sections (Figure S5A). This precluded us from conducting further IHC analysis using lineage markers. For FAC-hiPSC-derived embryos, we confirmed via IHC analysis (using an anti-GFP antibody) that they contained more human cells (Figures 6A, S5A, and S5B). We then stained additional sections using antibodies against TUJ1, EPCAM, SMA, CK8, and HNF3β (Figures 6B and S5C) and observed differentiation of FAC-hiPSCs into different cell lineages. In addition, these cells were found negative for OCT4, a pluripotency marker (data not shown). Moreover, the presence of human cells was further verified with a human-specific HuNu antibody staining (Figure 6B) and a sensitive genomic PCR assay using a human specific Alu sequence primer (Figure 6C; Table S2). Together, these results indicate that naive hiPSCs injected into pig blastocysts inefficiently contribute to chimera formation, and are only rarely detected in post-implantation pig embryos. An intermediate hPSC type (FAC-hiPSCs) showed better chimeric contribution and differentiated to several cell types in post-implantation human-pig chimeric embryos. It should be noted that the levels of chimerism from all hiPSCs, including the FAC-hiPSCs, in pig embryos were much lower when compare to rat-mouse chimeras (Figures 1C, 1E, S1A, and 1B), which may reflect the larger evolutionary distance between human-pig than between rat-mouse.
Discussion
Our study confirms that live rat-mouse chimeras with extensive contribution from naive rat PSCs can be generated. This is in contrast to earlier work in which rat ICMs were injected into mouse blastocysts (Gardner and Johnson, 1973). One possible explanation for this discrepancy is that cultured PSCs acquire artificial features that make them more proliferative and/or better able to survive than embryonic ICM cells, which in turn leads to their more robust xeno-engraftment capability in a mouse host. Rat-mouse chimeras generated by injecting donor rat PSCs into a mouse host were mouse-sized and developed into adulthood with apparently normal appearance and physiology. We further show in this study that a rat-mouse chimera could live a full mouse lifespan (about 2 years) and exhibit molecular signatures characteristic of aged cells. This demonstrates that cells from two different species, which diverged ∼18 million years ago, can live in a symbiotic environment and are able to support normal organismal aging. The fact that rat PSCs were able to contribute to the mouse gallbladder, an organ that is absent in the rat, highlights the importance of embryonic niches in orchestrating the specification, proliferation, and morphogenesis of tissues and organs during organismal development and evolutionary speciation (Izpisúa-Belmonte et al., 1992).
Previous interspecies blastocyst complementation experiments generated host embryos by crossing heterozygous mutant mouse strains, which were themselves generated through targeted gene disruption in germline competent ESCs. These experiments are labor intensive and time consuming. Moreover, only ∼25% of blastocysts derived from genetic crosses are homozygous mutants, posing a limitation for efficient complementation. CRISPR-Cas9 mediated zygote genome editing offers a faster and more efficient one-step process for generating mice carrying homozygous mutations, thereby providing a robust interspecies blastocyst complementation platform. Additionally, the multiplexing capability of CRISPR-Cas9 (Cong et al., 2013, Yang et al., 2015) could potentially be harnessed for multi-lineage complementation. For example, in the case of the pancreas, one might hope to eliminate both the pancreatic parenchyma and vasculature of the host to generate a more complete xenogeneic pancreas. Despite the advantages, there are several technical limitations of the CRISPR-Cas9 blastocyst complementation system that need to be overcome before unlocking its full potential. First, gene inactivation relies on the error-prone, non-homologous end joining (NHEJ) pathway, which is often unpredictable. In-frame mutations and mosaicism are among the factors that may affect outcomes. A more predictable targeted gene inactivation strategy that utilizes homologous recombination (HR) is still inefficient in the zygote. Second, each embryo must be injected twice when using this system and embryos must be cultured in vitro for several days before ET, thereby compromising embryo quality. Technical advancements that include a more robust gene-disruption strategy (e.g., targeted generation of frameshift mutations via homology independent targeted integration [Suzuki et al., 2016]), alternative CRISPR/Cas9 delivery methods, and improved culture conditions for manipulated embryos will likely help improve and optimize the generation of organogenesis-disabled hosts.
We observed a slower clearance of an intraperitoneally injected glucose load for Pdx1−/− than Pdx1+/− rat-mouse chimeras, while both were slower than wild-type mouse controls (Figure S2C). While this result may seem to contradict a previous report (Kobayashi et al., 2010), the discrepancy is likely due to the development of autoimmune type inflammation that is often observed in adult rat-mouse (chimeras made by injection of rat PSCs into mouse blastocyst, data not shown) (>7 months, this study) and mouse-rat chimeras (chimeras made by injection of mouse PSCs into rat blastocyst; H. Nakauchi, personal communication), which is less evident in young chimeras (∼8 weeks; Kobayashi et al. 2010). Interestingly though, we did observe a similarly slower clearance of glucose load in wild-type rats, although the initial spike was much lower in rats compared to mice or chimeras (Figure S2C). Thus, the rat cellular origin might also have played a role in the different GTT responses observed.
Rodent ESCs/iPSCs, considered as the gold standard cells for defining naive pluripotency, can robustly contribute to intra- and inter-species chimeras within rodent species. These and other results have led to the assumption that naive PSCs are the cells of choice when attempting to generate interspecies chimeras involving more disparate species. Here, we show that rodent PSCs fail to contribute to chimera formation when injected into pig blastocysts. This highlights the importance of other contributing factors underlying interspecies chimerism that may include, but not limited to, species-specific differences in epiblast and trophectoderm development, developmental kinetics, and maternal microenvironment.
To date, and taking into consideration all published studies that have used the mouse as the host species, it is probably appropriate to conclude that interspecies chimera formation involving hPSCs is inefficient (De Los Angeles et al., 2015). It has been argued that this apparent inefficiency results from species-specific differences between human and mouse embryogenesis. Therefore, studies utilizing other animal hosts would help address this important question. Here we focused on two species, pig and cattle, from a more diverse clade of mammals and found that naive and intermediate, but not primed, hiPSCs could robustly incorporate into pre-implantation host ICMs. Following ET, we observed, in general and similar to the mouse studies, low chimera forming efficiencies for all hiPSCs tested. Interestingly, injected hiPSCs seemed to negatively affect normal pig development as evidenced by the high proportion of growth retarded embryos. Nonetheless, we observed that FAC-hiPSCs, a putative intermediate PSC type between naive and primed pluripotent states, displayed a higher level of chimerism in post-implantation pig embryos. IHC analyses revealed that FAC-hiPSCs integrated and subsequently differentiated in host pig embryos (as shown by the expression of different lineage markers, and the lack of expression of the pluripotency marker OCT4). Whether the degree of chimerism conferred by FAC-hiPSCs could be sufficient for eliciting a successful interspecies human-pig blastocyst complementation, as demonstrated herein between rats and mice, remains to be demonstrated. Studies and approaches to improve the efficiency and level of hPSC interspecies chimerism (Wu et al., 2016), such as matching developmental timing, providing a selective advantage for donor hPSCs, generating diverse hPSCs with a higher chimeric potential and selecting a species evolutionarily closer to humans, among others parameters, will be needed.
The procedures and observations reported here on the capability of human pluripotent stem cells to integrate and differentiate in a ungulate embryo, albeit at a low level and efficiency, when optimized, may constitute a first step towards realizing the potential of interspecies blastocyst complementation with hPSCs. In particular, they may provide a better understanding of human embryogenesis, facilitate the development and implementation of humanized animal drug test platforms, as well as offer new insights on the onset and progression of human diseases in an in vivo setting. Ultimately, these observations also raise the possibility of xeno-generating transplantable human tissues and organs towards addressing the worldwide shortage of organ donors.
Author Contributions
J.W. and J.C.I.B. conceived the study. J.W. generated and characterized all naive and intermediate hiPSC lines. K.S. generated and characterized primed hiPSCs. J.W. and T.H. generated rat iPSCs. J.W., A.P.-L., T.Y., M.M.V., D.O., A.O., P.R., C.R.E., J.W., and P.M.R. performed immunohistochemistry analyses of mouse and pig embryos. K.S., T.Y., E.S., A.P.-L., and M.M.V. performed genotyping, genomic PCR, and genomic qPCR analyses. A.S., M.S., and J.P.L. performed mouse Cas9/sgRNA injection, blastocyst injection, and embryo transfer. Y.S.B., M.S., and M.V. prepared hiPSCs, performed morulae and blastocyst injections, and analyzed hiPSC contribution to cattle and ppig ICMs. H.W. produced parthenogenetic pig embryos. D.A.S., Y.S.B., and M.V. produced cattle embryos. Work at UC Davis and University of Murcia was performed under the supervision of P.J.R. and E.A.M., respectively. E.A.M., M.A.G., C.C., I.P., C.A.M., S.S.B., A.N., and J.R. designed, coordinated, performed, and analyzed data related to pig embryo collection, embryo culture, blastocyst injection, embryo transfer, and embryo recover. E.N.D., J.L., I.G., P.G., T.B., M.L.M.-M., and J.M.C. coordinated work between Salk, and University of Murcia. J.W., P.J.R., and J.C.I.B. wrote the manuscript.
Acknowledgments
J.C.I.B. dedicates this paper to Dr. Rafael Matesanz, Director of the Spain’s National Organ Transplant Organization. Rafael’s work has helped save thousands of patients in need of an organ. He constitutes a relentless inspiration for those of us trying to understand and alleviate human disease. The authors are grateful to Xiomara Lucas, Maria Dolores Ortega, Moises Gonzalvez, Jose Antonio Godinez, and Jesus Gomis for their assistance throughout this work. We thank the staff of the Agropor S.A. and Porcisan S.A. piggeries (Murcia, Spain) for the help and excellent management of animals. We thank Joan Rowe, Bret McNabb, Aaron Prinz, and Kent Parker and their crews for excellent assistance with embryo transfers and pig care at UC Davis. We thank Mako Yamamoto for help with mouse embryo dissection. We would like to thank Uri Manor of the Salk Waitt Advanced Biophotonics Core for technical advice on imaging analysis. We would like to thank the Salk Stem Cell Core for providing cell culture reagents. We would like to thank May Schwarz and Peter Schwarz for administrative help. We thank David O’Keefe for critical reading and editing of the manuscript. This experimental study was supported by The Fundación Séneca ( GERM 19892/GERM/15 ), Murcia, Spain. The MINECO is acknowledged for their grant-based support ( BES-2013-064087 and BES-2013-064069 ) (to C.A.M and A.N.). P.J.R was supported by a UC Davis Academic Senate New Research grant. Work in the laboratory of J.C.I.B. was supported by the UCAM, Fundacion Dr. Pedro Guillen, G. Harold and Leila Y. Mathers Charitable Foundation, and The Moxie Foundation.
Supplemental Information
Table S1. DNA Sequencing Results of CRISPR-Cas9-Mediated Gene Knockouts in Mice, Related to Figure 2
Table S2. gRNA Sequences, Primer Sequences for Genomic PCR, DNA Sequencing, and Genomic qPCR, Related to Figures 1, 2, 3, and 6
Table S3. Summary of the Embryo Transfer Experiments with Blastocysts Injected with Rat ESCs and Mouse iPSCs, Related to Figure 3
Table S4. Summary of hiPSCs ICM Incorporation after Injection into Cattle and Pig Blastocysts, Related to Figure 4
Table S5. Summary of Embryo Collection and Culture for In Vitro Generation of Blastocysts Used for Injections, Related to Figure 5
Table S6. Summary of the Embryo Transfer Experiments with Blastocysts Injected with hiPSCs, Related to Figure 5
Received: February 2, 2016; Received in revised form: October 30, 2016; Accepted: December 22, 2016; Published: January 26, 2017
© 2017 Elsevier Inc.
The Human-Pig Chimera Report From The Salk Institute
.
This section contains the 7 postings comprising the Original Proposal --
(1) 8/5/2016 -- “Clone Rights -- Involuntary Soldiers, Sex Slaves, Lab Rats, Etc. (including the text of the NIH proposed changes to the 2009 Human Stem-Cell Research Guidelines as published in the 8/6/2016 Federal Register)
(2) 8/5/2016 -- “What If Yale U’s 50% Human DNA Were All Dominant Traits???” (including the Discussion Outline for our 4/9/2008 meeting 8 years ago)
(3) 8/9/2016 -- “Marked Changes To The 2009 Human Stem-Cell Research Guidelines”
(4) 1/29/2017 -- “Human-Pig Chimeras -- Decent Behavior Despite Open Barn Door” (including 1/26/2017 Washington Post article)
(5) 1/31/2017 -- “Is the Fed Gov (NIH) Funding Nazi-Style Death Camps?” (to which it is respectfully suggested that the correct answer is “not yet, but soon”)
(6) 1/31/2017 -- “The Human-Pig Chimera Report From The Salk Institute” (ver batim text)
(7) 2/7/2017 -- “The Article in Britain’s ‘Nature’ About Rat-Mouse Chimeras” (ver batim text)
**********
These 7 postings were viewed 609 times before being transplanted here from the "Possible Topics for Future Meetings" section of this bulletin board.
This section contains the 7 postings comprising the Original Proposal --
(1) 8/5/2016 -- “Clone Rights -- Involuntary Soldiers, Sex Slaves, Lab Rats, Etc. (including the text of the NIH proposed changes to the 2009 Human Stem-Cell Research Guidelines as published in the 8/6/2016 Federal Register)
(2) 8/5/2016 -- “What If Yale U’s 50% Human DNA Were All Dominant Traits???” (including the Discussion Outline for our 4/9/2008 meeting 8 years ago)
(3) 8/9/2016 -- “Marked Changes To The 2009 Human Stem-Cell Research Guidelines”
(4) 1/29/2017 -- “Human-Pig Chimeras -- Decent Behavior Despite Open Barn Door” (including 1/26/2017 Washington Post article)
(5) 1/31/2017 -- “Is the Fed Gov (NIH) Funding Nazi-Style Death Camps?” (to which it is respectfully suggested that the correct answer is “not yet, but soon”)
(6) 1/31/2017 -- “The Human-Pig Chimera Report From The Salk Institute” (ver batim text)
(7) 2/7/2017 -- “The Article in Britain’s ‘Nature’ About Rat-Mouse Chimeras” (ver batim text)
**********
These 7 postings were viewed 609 times before being transplanted here from the "Possible Topics for Future Meetings" section of this bulletin board.
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- ↳ Original Proposal - Blood Money: Why the Powerful Turn a Blind Eye While China Kills Americans by Peter Schweizer - April 17
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- ↳ 10/26/2023: LETTER TO PRESIDENT BIDEN RE EXPORTATION OF AMERICAN JOBS AND SALE OF AMERICAN CROWN JEWELS TO PAY FOR CONSUMER-GOODS IMPORTS
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- ↳ Meeting Report – “Poverty, by America” by Prof. Matthew Desmond – AND Letter to President Biden re the United Nations War on Modern Slavery
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- ↳ Discussion Outline – “Poverty, by America” by Prof. Matthew Desmond – Sep 20
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- ↳ Discussion Outline - When Race Trumps Merit: How the Pursuit of Equity Sacrifices Excellence, Destroys Beauty, and Threatens Lives - Aug 16
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- ↳ Discussion Outline – The U.S. Supreme Court vs. Lower-Court National Injunctions – July 19
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- ↳ 6/21/2023: The Safer Communities Act of 2022 Proves To Be A Cruel Hoax Vis-a-vis Preventing School Shootings
- ↳ Reference Materials – The U.S. Supreme Court vs. Lower-Court National Injunctions – July 19
- ↳ Discussion Outline – Rabbi Van Lanckton’s 16 Gun-Safety Ideas, Providing Our Schools The Same Protection As Airports & Office Buildings, Etc. – June 21
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- ↳ Discussion Outline – Oliver Stone’s “Nuclear Now” + “A Bright Future: How Some Countries Have Solved Climate Change and the Rest Can Follow” – May 17
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- ↳ Meeting Report – “Marked for Life: One Man’s Fight for Justice from the Inside” – April 19
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- ↳ Discussion Outline – The Coddling of the American Mind: How Good Intentions and Bad Ideas Are Setting Up a Generation for Failure – March 15
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- ↳ Reference Materials – The Coddling of the American Mind: How Good Intentions and Bad Ideas Are Setting Up a Generation for Failure – March 15
- ↳ Discussion Outline – Future Peace: Technology, Aggression, and the Rush to War by Maj. Gen. (Ret.) Robert Latiff – Feb 15
- ↳ Original Proposal – Future Peace: Technology, Aggression, and the Rush to War by Maj. Gen. (Ret.) Robert Latiff – Feb 15
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- ↳ Discussion Outline – “Bibi: My Story” by Israeli Prime Minister Benjamin Netanyahu – Jan 18
- ↳ Original Proposal – “Bibi: My Story” by Israeli Prime Minister Benjamin Netanyahu – Jan 18
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- ↳ Discussion Outline – “Doom: The Politics of Catastrophe” by Prof. Niall Ferguson (husband of Ayaan Hirsi Ali) – Dec 14
- ↳ Original Proposal – “Doom: The Politics of Catastrophe” by Prof. Niall Ferguson (husband of Ayaan Hirsi Ali) – Dec 14
- ↳ Participant Comments – “Doom: The Politics of Catastrophe” by Prof. Niall Ferguson (husband of Ayaan Hirsi Ali) – Dec 14
- ↳ Reference Materials – “Doom: The Politics of Catastrophe” by Prof. Niall Ferguson (husband of Ayaan Hirsi Ali) – Dec 14
- ↳ Discussion Outline – A Pox On Both Former Sen. Phil Gramm and Pres. Biden Re Jonathan Kozol’s “Restoration of Apartheid Schooling in America” – Nov 16
- ↳ Original Proposal – A Pox On Both Former Sen. Phil Gramm and Pres. Biden Re Jonathan Kozol’s “Restoration of Apartheid Schooling in America” – Nov 16
- ↳ Participant Comments – A Pox On Both Former Sen. Phil Gramm and Pres. Biden Re Jonathan Kozol’s “Restoration of Apartheid Schooling in America” – Nov 16
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- ↳ Discussion Outline – Volt Rush: The Winners and Losers in the Race to Go Green – Oct 19
- ↳ Original Proposal – Volt Rush: The Winners and Losers in the Race to Go Green – Oct 19
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- ↳ Reference Materials – Volt Rush: The Winners and Losers in the Race to Go Green – Oct 19
- ↳ Discussion Outline – What We Owe The Future by Oxford U. Prof. William MacAskill – Sept 21
- ↳ Original Proposal – What We Owe The Future by Oxford U. Prof. William MacAskill – Sept 21
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- ↳ Discussion Outline - “The Dumbest Generation Grows Up: From Stupefied Youth to Dangerous Adults” by Prof. Mark Bauerlein - Aug 17
- ↳ Original Proposal - “The Dumbest Generation Grows Up: From Stupefied Youth to Dangerous Adults” by Prof. Mark Bauerlein - Aug 17
- ↳ Participant Comments - “The Dumbest Generation Grows Up: From Stupefied Youth to Dangerous Adults” by Prof. Mark Bauerlein - Aug 17
- ↳ Reference Materials - “The Dumbest Generation Grows Up: From Stupefied Youth to Dangerous Adults” by Prof. Mark Bauerlein - Aug 17
- ↳ Discussion Outline - Climate Change and "How The World Really Works: The Science Behind How We Got Here and Where We’re Going" by Prof. Vaclav Smil - July 20
- ↳ Original Proposal - Climate Change and "How The World Really Works: The Science Behind How We Got Here and Where We’re Going" by Prof. Vaclav Smil - July 20
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- ↳ Discussion Outline – Caste: The Origins Of Our Discontents - Oprah’s Book Club – June 15
- ↳ Original Proposal – Caste: The Origins Of Our Discontents - Oprah’s Book Club – June 15
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- ↳ Discussion Outline – “Red-Handed: How American Elites Get Rich Helping China Win” by Peter Schweizer – May 18
- ↳ Original Proposal – “Red-Handed: How American Elites Get Rich Helping China Win” by Peter Schweizer – May 18
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- ↳ Discussion Outline - The Dying Concept of Citizenship & America’s Southern Border – April 20
- ↳ Original Proposal - The Dying Concept of Citizenship & America’s Southern Border – April 20
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- ↳ Public-Policy Letters Sent to the European Union President & the NATO Secretary General – America’s 1994 Written & Signed Guarantee Of Ukraine’s Independence and Territorial Integrity For Ukraine Surrendering Its 1,900 Nuclear Missiles – March 16
- ↳ Discussion Outline – America’s 1994 Written & Signed Guarantee Of Ukraine’s Independence and Territorial Integrity For Ukraine Surrendering Its 1,900 Nuclear Missiles – March 16
- ↳ Original Proposal – America’s 1994 Written & Signed Guarantee Of Ukraine’s Independence and Territorial Integrity For Ukraine Surrendering Its 1,900 Nuclear Missiles – March 16
- ↳ Participant Comments – America’s 1994 Written & Signed Guarantee Of Ukraine’s Independence and Territorial Integrity For Ukraine Surrendering Its 1,900 Nuclear Missiles – March 16
- ↳ Short Quiz and Suggested Answers – America’s 1994 Written & Signed Guarantee Of Ukraine’s Independence and Territorial Integrity For Ukraine Surrendering Its 1,900 Nuclear Missiles – March 16
- ↳ Reference Materials – America’s 1994 Written & Signed Guarantee Of Ukraine’s Independence and Territorial Integrity For Ukraine Surrendering Its 1,900 Nuclear Missiles – March 16
- ↳ Discussion Outline – NYC Harvard Club Book Promotion – “Our Broken Elections: How the Left Changed the Way You Vote” – Feb 16
- ↳ Original Proposal – NYC Harvard Club Book Promotion – “Our Broken Elections: How the Left Changed the Way You Vote” – Feb 16
- ↳ Participant Comments – NYC Harvard Club Book Promotion - “Our Broken Elections: How the Left Changed the Way You Vote” – Feb 16
- ↳ Reference Materials – NYC Harvard Club Book Promotion – “Our Broken Elections: How the Left Changed the Way You Vote” – Feb 16
- ↳ Discussion Outline – The Deficit Myth by Democratic Party Economic Guru, Prof. Stephanie Kelton – Jan 19
- ↳ Original Proposal – The Deficit Myth by Democratic Party Economic Guru, Prof. Stephanie Kelton – Jan 19
- ↳ Discussion Outline – President Obama’s Dept of Energy Under-Secretary for Science (Prof. Steven Koonin) on “Unsettled: What Climate Science Tells Us, What It Doesn’t, and Why It Matters” – Dec 8
- ↳ Participant Comments – The Deficit Myth by Democratic Party Economic Guru, Prof. Stephanie Kelton – Jan 19
- ↳ Reference Materials – The Deficit Myth by Democratic Party Economic Guru, Prof. Stephanie Kelton – Jan 19
- ↳ Original Proposal – President Obama’s Dept of Energy Under-Secretary for Science (Prof. Steven Koonin) on “Unsettled: What Climate Science Tells Us, What It Doesn’t, and Why It Matters” – Dec 8
- ↳ Participant Comments – President Obama’s Dept of Energy Under-Secretary for Science (Prof. Steven Koonin) on “Unsettled: What Climate Science Tells Us, What It Doesn’t, and Why It Matters” – Dec 8
- ↳ Reference Materials – President Obama’s Dept of Energy Under-Secretary for Science (Prof. Steven Koonin) on “Unsettled: What Climate Science Tells Us, What It Doesn’t, and Why It Matters” – Dec 8
- ↳ CONTINUATION OF THE PREVIOUS SECTION
- ↳ Discussion Outline – An Elegant Defense: The Extraordinary New Science Of The Immune System – Nov 10
- ↳ Original Proposal – An Elegant Defense: The Extraordinary New Science Of The Immune System – Nov 10
- ↳ Participant Comments – An Elegant Defense: The Extraordinary New Science Of The Immune System – Nov 10
- ↳ Reference Materials – An Elegant Defense: The Extraordinary New Science Of The Immune System – Nov 10
- ↳ Discussion Outline – Revisiting The Issue Of Charter Schools: Stanford University vs. Stanford’s Hoover Institution – Oct 13
- ↳ Original Proposal – Revisiting The Issue Of Charter Schools: Stanford University vs. Stanford’s Hoover Institution – Oct 13
- ↳ Participant Comments – Revisiting The Issue Of Charter Schools: Stanford University vs. Stanford’s Hoover Institution – Oct 13
- ↳ Reference Materials – Revisiting The Issue Of Charter Schools: Stanford University vs. Stanford’s Hoover Institution – Oct 13
- ↳ Discussion Outline – Discrimination and Disparities by Thomas Sowell – Sept 8
- ↳ Original Proposal – Discrimination and Disparities by Thomas Sowell – Sept 8
- ↳ Participant Comments – Discrimination and Disparities by Thomas Sowell – Sept 8
- ↳ Reference Materials – Discrimination and Disparities by Thomas Sowell – Sept 8
- ↳ Discussion Outline - The Non-Partisan Public-Policy Issues of Whether, For Example, Michael Lewis’ “The Premonition: A Pandemic Story” Is A Classic Political “Hit Piece” and Whether, As Such, It Should Be (vs. Is) Protected by Freedom Of Speech - Aug 11
- ↳ Original Proposal – The Non-Partisan Public-Policy Issues of Whether, For Example, Michael Lewis’ “The Premonition: A Pandemic Story” Is A Classic Political “Hit Piece” and Whether, As Such, It Should Be (vs. Is) Protected by “Freedom Of Speech” – Aug 11
- ↳ Participant Comments – The Non-Partisan Public-Policy Issues of Whether, For Example, Michael Lewis’ “The Premonition: A Pandemic Story” Is A Classic Political “Hit Piece” and Whether, As Such, It Should Be (vs. Is) Protected by Freedom Of Speech – Aug 11
- ↳ Discussion Outline – “1620: A Critical Response To The 1619 Project” by Peter Wood – July 14
- ↳ Reference Materials – The Non-Partisan Public-Policy Issues of Whether, For Example, Michael Lewis’ “The Premonition: A Pandemic Story” Is A Classic Political “Hit Piece” and Whether, As Such, It Should Be (vs. Is) Protected by Freedom Of Speech – Aug 11
- ↳ Original Proposal – “1620: A Critical Response To The 1619 Project” by Peter Wood – July 14
- ↳ Participant Comments – “1620: A Critical Response To The 1619 Project” by Peter Wood – July 14
- ↳ Reference Materials – “1620: A Critical Response To The 1619 Project” by Peter Wood – July 14
- ↳ Meeting Report – “Predict & Surveil: Data, Discretion & the Future of Policing” by Prof. Sarah Brayne – June 9
- ↳ Discussion Outline – “Predict & Surveil: Data, Discretion & the Future of Policing” by Prof. Sarah Brayne – June 9
- ↳ Original Proposal – “Predict & Surveil: Data, Discretion & the Future of Policing” by Prof. Sarah Brayne – June 9
- ↳ Participant Comments – “Predict & Surveil: Data, Discretion & the Future of Policing” by Prof. Sarah Brayne – June 9
- ↳ Resource Materials – “Predict & Surveil: Data, Discretion & the Future of Policing” by Prof. Sarah Brayne – June 9
- ↳ Discussion Outline – “How To Avoid A Climate Disaster: The Solutions We Have and the Breakthroughs We Need” by Bill Gates – May 12
- ↳ Original Proposal – “How To Avoid A Climate Disaster: The Solutions We Have and the Breakthroughs We Need” by Bill Gates – May 12
- ↳ Participant Comments – “How To Avoid A Climate Disaster: The Solutions We Have and the Breakthroughs We Need” by Bill Gates – May 12
- ↳ Reference Materials – “How To Avoid A Climate Disaster: The Solutions We Have and the Breakthroughs We Need” by Bill Gates – May 12
- ↳ Discussion Outline – “Cancel Culture: The Latest Attack on Free Speech and Due Process” by Prof. Alan Dershowitz – April 7
- ↳ Original Proposal – “Cancel Culture: The Latest Attack on Free Speech and Due Process” by Prof. Alan Dershowitz – April 7
- ↳ Participant Comments – “Cancel Culture: The Latest Attack on Free Speech and Due Process” by Prof. Alan Dershowitz – April 7
- ↳ Reference Materials – “Cancel Culture: The Latest Attack on Free Speech and Due Process” by Prof. Alan Dershowitz – April 7
- ↳ Discussion Outline – “The New Map: Energy, Climate & the Clash of Nations” by Pulitzer-Prize Winner Daniel Yergin – March 10
- ↳ Original Proposal – “The New Map: Energy, Climate & the Clash of Nations” by Pulitzer-Prize Winner Daniel Yergin – March 10
- ↳ Participant Comments – “The New Map: Energy, Climate & the Clash of Nations” by Pulitzer-Prize Winner Daniel Yergin – March 10
- ↳ Resource Materials – “The New Map: Energy, Climate & the Clash of Nations” by Pulitzer-Prize Winner Daniel Yergin – March 10
- ↳ Discussion Outline - “Enlightenment Now: The Case for Reason, Science, Humanism, and Progress by Prof. Steven Pinker – Feb 10
- ↳ Reference Materials - “Enlightenment Now: The Case for Reason, Science, Humanism, and Progress by Prof. Steven Pinker – Feb 10
- ↳ Original Proposal - “Enlightenment Now: The Case for Reason, Science, Humanism, and Progress by Prof. Steven Pinker – Feb 10
- ↳ Participant Comments - “Enlightenment Now: The Case for Reason, Science, Humanism, and Progress by Prof. Steven Pinker – Feb 10
- ↳ Meeting Report – Civilization: The West and the Rest by Prof. Niall Ferguson – Jan 13
- ↳ Discussion Outline – Civilization: The West and the Rest by Prof. Niall Ferguson – Jan 13
- ↳ Original Proposal – Civilization: The West and the Rest by Prof. Niall Ferguson – Jan 13
- ↳ Participant Comments – Civilization: The West and the Rest by Prof. Niall Ferguson – Jan 13
- ↳ Reference Materials – Civilization: The West and the Rest by Prof. Niall Ferguson – Jan 13
- ↳ Discussion Outline - Great Society: A New History by Amity Shlaes - Dec 9
- ↳ Original Proposal - Great Society: A New History by Amity Shlaes - Dec 9
- ↳ Participant Comments - Great Society: A New History by Amity Shlaes - Dec 9
- ↳ Reference Materials - Great Society: A New History by Amity Shlaes - Dec 9
- ↳ Discussion Outline – “The Square and The Tower: Networks and Power, from the Freemasons to Facebook” by Prof. Niall Ferguson – Nov 11
- ↳ Original Proposal – “The Square and The Tower: Networks and Power, from the Freemasons to Facebook” by Prof. Niall Ferguson – Nov 11
- ↳ Participant Comments – “The Square and The Tower: Networks and Power, from the Freemasons to Facebook” by Prof. Niall Ferguson – Nov 11
- ↳ Reference Materials – “The Square and The Tower: Networks and Power, from the Freemasons to Facebook” by Prof. Niall Ferguson – Nov 11
- ↳ Discussion Outline – The Human Network: How Your Social Position Determines Your Power, Beliefs and Behaviors By Stanford U. Prof Matthew Jackson – Oct 14
- ↳ Original Proposal – The Human Network: How Your Social Position Determines Your Power, Beliefs and Behaviors By Stanford U. Prof Matthew Jackson – Oct 14
- ↳ Participant Comments – The Human Network: How Your Social Position Determines Your Power, Beliefs and Behaviors By Stanford U. Prof Matthew Jackson – Oct 14
- ↳ Reference Materials – The Human Network: How Your Social Position Determines Your Power, Beliefs and Behaviors By Stanford U. Prof Matthew Jackson – Oct 14
- ↳ Discussion Outline - The Revolutionary Lives of Malcolm X and Martin Luther King by Prof. Peniel Joseph - Sep 9
- ↳ Original Proposal - The Revolutionary Lives of Malcolm X and Martin Luther King by Prof. Peniel Joseph - Sep 9
- ↳ Participant Comments - The Revolutionary Lives of Malcolm X and Martin Luther King by Prof. Peniel Joseph - Sep 9
- ↳ Reference Materials - The Revolutionary Lives of Malcolm X and Martin Luther King by Prof. Peniel Joseph - Sep 9
- ↳ Discussion Outline – "Tightrope: Americans Reaching For Hope" by Pulitzer-Prize Winners Sheryl WuDunn and Husband, NY Times Columnist Nicholas Kristof – Aug 12
- ↳ Original Proposal – "Tightrope: Americans Reaching For Hope" by Pulitzer-Prize Winners Sheryl WuDunn and Husband, NY Times Columnist Nicholas Kristof – Aug 12
- ↳ Discussion Outline – “The Age of Addiction” by Prof. David Courtwright – July 8
- ↳ Participant Comments – "Tightrope: Americans Reaching For Hope" by Pulitzer-Prize Winners Sheryl WuDunn and Husband, NY Times Columnist Nicholas Kristof – Aug 12
- ↳ Reference Materials – "Tightrope: Americans Reaching For Hope" by Pulitzer-Prize Winners Sheryl WuDunn and Husband, NY Times Columnist Nicholas Kristof – Aug 12
- ↳ Participant Comments – “The Age of Addiction: How Bad Habits Became Big Business” by Prof. David Courtwright – July 8
- ↳ Original Proposal – “The Age of Addiction: How Bad Habits Became Big Business” by Prof. David Courtwright – July 8
- ↳ Reference Materials – “The Age of Addiction: How Bad Habits Became Big Business” by Prof. David Courtwright – July 8
- ↳ 6/3/2020: CALL TO ACTION – ONLY 10 MINUTES NEEDED FOR YOU TO PARTICIPATE – “SIX DEGREES OF SEPARATION” E-MAIL CAMPAIGN TO ADDRESS THE ROOT CAUSE OF RACISM (VS. ONLY A MERE SYMPTOM) – AMERICA’S PERMANENT 30% UNDER-CASTE
- ↳ Discussion Outline – Jonathan Kozol “The Shame of the Nation: The Restoration of Apartheid Schooling in America” and Free Tuition for Public Colleges and Vocational Schools – June 3
- ↳ Original Proposal – Jonathan Kozol “The Shame of the Nation: The Restoration of Apartheid Schooling in America” and Free Tuition for Public Colleges and Vocational Schools – Mtg Date TBD
- ↳ Participant Comments – Jonathan Kozol “The Shame of the Nation: The Restoration of Apartheid Schooling in America” and Free Tuition for Public Colleges and Vocational Schools – Mtg Date TBD
- ↳ Reference Materials – Jonathan Kozol “The Shame of the Nation: The Restoration of Apartheid Schooling in America” and Free Tuition for Public Colleges and Vocational Schools – June 3
- ↳ Mail Campaign to ABC’s The View – Money in Politics – March 18
- ↳ Discussion Outline – Money in Politics – March 18
- ↳ Original Proposal - Money in Politics: Michael Bloomberg & Tom Steyer, et al. - March 18
- ↳ Participant Comments - Money in Politics: Michael Bloomberg & Tom Steyer, et al. - March 18
- ↳ Meeting WED Evening Feb 19 – Proposed E-mail Campaign Re “Hunger in America” – Your Opportunity To Strike A Blow For BASIC HUMAN DECENCY
- ↳ Feb 19 Meeting Report – Proposed E-mail Campaign Re “Hunger in America”
- ↳ Original Proposal – Utah Taxing Groceries of Our Neighbors Living on Less Than $2.00/Day – Feb 19
- ↳ Participant Comments – Utah Taxing Groceries of Our Neighbors Living on Less Than $2.00/Day – Feb 19
- ↳ Reference Materials – Utah Taxing Groceries of Our Neighbors Living on Less Than $2.00/Day – Feb 19
- ↳ CALL TO ACTION – ONLY 5 MINUTES NEEDED FOR YOU TO PARTICIPATE – “SIX-DEGREES-OF-SEPARATION” E-MAIL CAMPAIGN TO SOLVE THE PALESTINIAN ISSUE (AND AVOID “THE TWILIGHT OF THE HUMANS” - Jan 15
- ↳ Original Proposal – “REPRISE: A Marshall-Type Plan For Palestinians” – Jan 15
- ↳ Suggested Discussion Outline – “REPRISE: A Marshall-Type Plan For Palestinians” – Jan 15
- ↳ Participant Comments – “REPRISE: A Marshall-Type Plan For Palestinians” – Jan 15
- ↳ Reference Materials – “REPRISE: A Marshall-Type Plan For Palestinians” – Jan 15
- ↳ CALL TO ACTION – “SIX-DEGREES-OF-SEPARATION” E-MAIL CAMPAIGN TO SAVE THE U.S. GOVERNMENT $86 BILLION/YEAR BY ADOPTING MEDICARE-FOR-ALL – (only 5 minutes needed to participate)
- ↳ Discussion Outline – “The Price We Pay: What Broke American Health Care And How To Fix It” by Johns Hopkins Surgeon and Prof. of Health Policy Marty Markary – Dec 11
- ↳ Participant Comments – “The Price We Pay: What Broke American Health Care And How To Fix It” by Johns Hopkins Surgeon and Prof. of Health Policy Marty Markary – Dec 11
- ↳ Original Proposal – “The Price We Pay: What Broke American Health Care And How To Fix It” by Johns Hopkins Surgeon and Prof. of Health Policy Marty Markary – Dec 11
- ↳ Reference Materials – “The Price We Pay: What Broke American Health Care And How To Fix It” by Johns Hopkins Surgeon and Prof. of Health Policy Marty Markary – Dec 11
- ↳ CALL TO ACTION – “SIX-DEGREES-OF-SEPARATION” E-MAIL CAMPAIGN TO PROTECT POSSIBLE GLOBAL-WARMING SOLUTION (HYDROGEN EXTRACTION) FROM BEING KILLED!!! – (only 5 minutes needed to participate)
- ↳ Discussion Outline - Possible Global Warming Solution (Hydrogen Extraction) In Danger Of Being Killed!!! - Nov 13
- ↳ Original Proposal - Possible Global Warming Solution (Hydrogen Extraction) In Danger Of Being Killed!!! - Nov 13
- ↳ Participant Comments - Possible Global Warming Solution (Hydrogen Extraction) In Danger Of Being Killed!!! - Nov 13
- ↳ Reference Materials - Possible Global Warming Solution (Hydrogen Extraction) In Danger Of Being Killed!!! - Nov 13
- ↳ Suggested Discussion Outline - “Tech Titans Of China: How China’s Tech Sector Is Challenging The World By Innovating Faster, Working Harder and Going Global by Rebecca A. Fannin – Oct 16
- ↳ Original Proposal - “Tech Titans Of China: How China’s Tech Sector Is Challenging The World By Innovating Faster, Working Harder and Going Global by Rebecca A. Fannin – Oct 16
- ↳ Participant Comments - “Tech Titans Of China: How China’s Tech Sector Is Challenging The World By Innovating Faster, Working Harder and Going Global by Rebecca A. Fannin - Oct 16
- ↳ Reference Materials - “Tech Titans Of China: How China’s Tech Sector Is Challenging The World By Innovating Faster, Working Harder and Going Global by Rebecca A. Fannin - Oct 16
- ↳ CALL TO ACTION – Six-Degrees-Of-Separation-Email-Campaign – A Suggestion To President Trump Re How To Support the United Nations 19-year Campaign Against “Trafficking In Persons, Especially Women and Children” – only 5 minutes needed to participate
- ↳ Suggested Discussion Outline - Sex Trafficking: Inside the Business of Modern Slavery - Sep 18
- ↳ Original Proposal – Sex Trafficking: Inside the Business of Modern Slavery – Sep 18
- ↳ Participant Comments – Sex Trafficking: Inside the Business of Modern Slavery – Sep 18
- ↳ Reference Materials – Sex Trafficking: Inside the Business of Modern Slavery – Sep 18
- ↳ Participant Comments – Brown Girl Dreaming by Jacqueline Woodson – July 31
- ↳ Suggested Discussion Outline – Brown Girl Dreaming by Jacqueline Woodson – July 31
- ↳ Original Proposal – Brown Girl Dreaming by Jacqueline Woodson – July 31
- ↳ Reference Materials – Brown Girl Dreaming by Jacqueline Woodson – July 31
- ↳ Suggested Discussion Outline -- "The Great Revolt: Inside the Populist Coalition Reshaping American Politics” -- June 13
- ↳ Original Proposal -- "The Great Revolt: Inside the Populist Coalition Reshaping American Politics” -- June 13
- ↳ Short Quiz -- "The Great Revolt: Inside the Populist Coalition Reshaping American Politics” -- June 13
- ↳ Reference Materials -- "The Great Revolt: Inside the Populist Coalition Reshaping American Politics” -- June 13
- ↳ The Quartet – Three E-mail Campaigns “Approved” – May 16
- ↳ Suggested Discussion Outline - "The Quartet: Orchestrating the Second American Revolution, 1783-1789" by Prof. Joseph J. Ellis – May 16
- ↳ Original Proposal - "The Quartet: Orchestrating the Second American Revolution, 1783-1789" by Prof. Joseph J. Ellis – May 16
- ↳ Reference Materials – "The Quartet: Orchestrating the Second American Revolution, 1783-1789" by Prof. Joseph J. Ellis – May 16
- ↳ Participant Comments – "The Quartet: Orchestrating the Second American Revolution, 1783-1789" by Prof. Joseph J. Ellis – May 16
- ↳ Cancellation of Official Status of April 11 Meeting on Joseph Califano’s “Our Damaged Democracy: We The People Must Act” + John Karls’ Research on Harvard as “Cambridge University in New England” 1636-1816
- ↳ Original Proposal - Our Damaged Democracy: We The People Must Act by Joseph Califano Jr. - April 11
- ↳ CALL TO ACTION – “SIX-DEGREES-OF-SEPARATION” E-MAIL CAMPAIGN TO HOLD CHINA RESPONSIBLE FOR NORTH KOREAN ACTIONS (only 5 minutes needed to participate)
- ↳ Suggested Discussion Outline - “American Tianxia: Chinese Money, American Power and the End of History” by Prof. Salvatore Babones - March 14
- ↳ Original Proposal - “American Tianxia: Chinese Money, American Power and the End of History” by Prof. Salvatore Babones - March 14
- ↳ Participant Comments - “American Tianxia: Chinese Money, American Power and the End of History” by Prof. Salvatore Babones - March 14
- ↳ Reference Materials - “American Tianxia: Chinese Money, American Power and the End of History” by Prof. Salvatore Babones - March 14
- ↳ Suggested Discussion Outline - “$2.00 a Day: Living on Almost Nothing in America” - Feb 7
- ↳ Original Proposal - “$2.00 a Day: Living on Almost Nothing in America” - Feb 7
- ↳ Participant Comments - “$2.00 a Day: Living on Almost Nothing in America” - Feb 7
- ↳ Reference Materials - “$2.00 a Day: Living on Almost Nothing in America” - Feb 7
- ↳ Meeting Cancellation - The Working Class Republican: Ronald Reagan and the Return of Blue Collar Conservatism - Jan 10
- ↳ Original Proposal - The Working Class Republican: Ronald Reagan and the Return of Blue Collar Conservatism - Jan 10
- ↳ Reference Materials - The Working Class Republican: Ronald Reagan and the Return of Blue Collar Conservatism - Jan 10
- ↳ Suggested Discussion Outline - Heretic: Why Islam Needs a Reformation Now by Ayaan Hirsi Ali - Dec 13
- ↳ Original Proposal - Heretic: Why Islam Needs a Reformation Now by Ayaan Hirsi Ali - Dec 13
- ↳ Participant Comments - Heretic: Why Islam Needs a Reformation Now by Ayaan Hirsi Ali - Dec 13
- ↳ Reference Materials - Heretic: Why Islam Needs a Reformation Now by Ayaan Hirsi Ali - Dec 13
- ↳ Suggested Discussion Outline - Strangers in Their Own Land: Anger and Mourning by the American Right: A Journey to the Heart of Our Political Divide - Nov 8
- ↳ Original Proposal - Strangers in Their Own Land: Anger and Mourning by the American Right: A Journey to the Heart of Our Political Divide - Nov 8
- ↳ Participant Comments - Strangers in Their Own Land: Anger and Mourning by the American Right: A Journey to the Heart of Our Political Divide - Nov 8
- ↳ Reference Materials - Strangers in Their Own Land: Anger and Mourning by the American Right: A Journey to the Heart of Our Political Divide - Nov 8
- ↳ Suggested Discussion Outline - A Fine Mess: A Global Quest for a Simpler, Fairer, and More Efficient Tax System by T.R. Reid – Oct 4
- ↳ Original Proposal - A Fine Mess: A Global Quest for a Simpler, Fairer, and More Efficient Tax System by T.R. Reid – Oct 4
- ↳ Participant Comments - A Fine Mess: A Global Quest for a Simpler, Fairer, and More Efficient Tax System by T.R. Reid – Oct 4
- ↳ Reference Materials - A Fine Mess: A Global Quest for a Simpler, Fairer, and More Efficient Tax System by T.R. Reid – Oct 4
- ↳ Suggested Discussion Outline - The War On Cops: How the New Attack on Law & Order Makes Everyone Less Safe by Heather MacDonald - Sep 6
- ↳ Original Proposal - The War On Cops: How the New Attack on Law & Order Makes Everyone Less Safe by Heather MacDonald - Sep 6
- ↳ Participant Comments - The War On Cops: How the New Attack on Law & Order Makes Everyone Less Safe by Heather MacDonald - Sep 6
- ↳ Reference Materials - The War On Cops: How the New Attack on Law & Order Makes Everyone Less Safe by Heather MacDonald - Sep 6
- ↳ Meeting Cancellation - American Amnesia: How The War On American Government Led Us To Forget What Made America Prosper – For Aug 9
- ↳ Original Proposal - American Amnesia: How The War On American Government Led Us To Forget What Made America Prosper – For Aug 9
- ↳ Reference Materials - American Amnesia: How The War On American Government Led Us To Forget What Made America Prosper – For Aug 9
- ↳ CALL TO ACTION – "SIX-DEGREES-OF-SEPARATION" E-MAIL CAMPAIGN RE SAVING THE U.S. GOV $300 BILLION/YEAR BY ENACTING “MEDICARE FOR ALL” – (only 5 minutes needed to participate)
- ↳ Original Proposal - An American Sickness: How Healthcare Became Big Business and How You Can Take It Back by Elisabeth Rosenthal – For July 12
- ↳ Suggested Discussion Outline - An American Sickness: How Healthcare Became Big Business and How You Can Take It Back by Elisabeth Rosenthal – For July 12
- ↳ Participant Comments - An American Sickness: How Healthcare Became Big Business and How You Can Take It Back by Elisabeth Rosenthal – For July 12
- ↳ Reference Materials - An American Sickness: How Healthcare Became Big Business and How You Can Take It Back by Elisabeth Rosenthal – For July 12
- ↳ Suggested Discussion Outline - How Everything Became War and the Military Became Everything by Rosa Brooks – June 7
- ↳ Original Proposal - How Everything Became War and the Military Became Everything by Rosa Brooks – June 7
- ↳ Participant Comments - How Everything Became War and the Military Became Everything by Rosa Brooks – June 7
- ↳ Reference Materials - How Everything Became War and the Military Became Everything by Rosa Brooks – June 7
- ↳ Discussion Outline – Authoritarian Rule by Our Intelligence Services – May 10
- ↳ Original Proposal – Authoritarian Rule by Our Intelligence Services – May 10
- ↳ Participant Comments – Authoritarian Rule by Our Intelligence Services – May 10
- ↳ Reference Materials – Authoritarian Rule by Our Intelligence Services – May 10
- ↳ April 12 Meeting Cancellation
- ↳ Original Proposal - Thank You For Being Late: An Optimist’s Guide To Thriving in an Age of Accelerations – For April 12th
- ↳ Reference Materials - Thank You For Being Late: An Optimist’s Guide To Thriving in an Age of Accelerations – For April 12th
- ↳ Participant Comments - Thank You For Being Late: An Optimist’s Guide To Thriving in an Age of Accelerations – For April 12th
- ↳ Discussion Outline – Killing Millions of Sesame Street Miss Piggy’s For The Human Organs – March 8
- ↳ Original Proposal – Killing Millions of Sesame Street Miss Piggy’s For The Human Organs – March 8
- ↳ Participant Comments – Killing Millions of Sesame Street Miss Piggy’s For The Human Organs – March 8
- ↳ Original Proposal Reference Materials – Killing Millions of Sesame Street Miss Piggy’s For The Human Organs – March 8
- ↳ CALL TO ACTION - OPPOSING THE WANTON DESTRUCTION OF GREAT SALT LAKE – FEB 8TH
- ↳ Discussion Outline - The Mormon Church Condoning The Wanton Destruction Of Great Salt Lake – Feb 8th
- ↳ Original Proposal - The Mormon Church Condoning The Wanton Destruction Of Great Salt Lake – Feb 8th
- ↳ Participant Comments - The Mormon Church Condoning The Wanton Destruction Of Great Salt Lake – Feb 8th
- ↳ Reference Materials - The Mormon Church Condoning The Wanton Destruction Of Great Salt Lake – Feb 8th
- ↳ Discussion Outline – Being Mortal: Medicine and What Matters In The End – Jan 11
- ↳ Original Proposal – Being Mortal: Medicine and What Matters In The End – Jan 11
- ↳ Participant Comments – Being Mortal: Medicine and What Matters In The End – Jan 11
- ↳ Reference Materials – Being Mortal: Medicine and What Matters In The End – Jan 11
- ↳ Discussion Outline – Makers and Takers: The Rise of Finance and the Fall of American Business – Dec 14
- ↳ Original Proposal - Makers and Takers: The Rise of Finance and the Fall of American Business – Dec 14
- ↳ Participant Comments - Makers and Takers: The Rise of Finance and the Fall of American Business – Dec 14
- ↳ Reference Materials - Makers and Takers: The Rise of Finance and the Fall of American Business – Dec 14
- ↳ Discussion Outline - The Terror Years: From Al-Qaeda to the Islamic State – Nov 16
- ↳ Original Proposal - The Terror Years: From Al-Qaeda to the Islamic State – Nov 16
- ↳ Participant Comments – The Terror Years: From Al-Qaeda to the Islamic State – Nov 16
- ↳ Reference Materials - The Terror Years: From Al-Qaeda to the Islamic State – Nov 16
- ↳ Discussion Outline - Helping Children Succeed: What Works and Why - Oct 19
- ↳ Participant Comments – Helping Children Succeed: What Works and Why - Oct 19
- ↳ Original Proposal - Helping Children Succeed: What Works and Why - Oct 19
- ↳ Reference Materials – Helping Children Succeed: What Works and Why - Oct 19
- ↳ Discussion Outline – Hillbilly Elegy: A Memoir of Family and Culture in Crisis - Sep 14
- ↳ Original Proposal – Hillbilly Elegy: A Memoir of Family and Culture in Crisis - Sep 14
- ↳ Participant Comments – Hillbilly Elegy: A Memoir of Family and Culture in Crisis - Sep 14
- ↳ Reference Materials – Hillbilly Elegy: A Memoir of Family and Culture in Crisis - Sep 14
- ↳ Discussion Outline - San Bernardino and The F.B.I. vs. Apple – Aug 10
- ↳ Original Proposal – San Bernardino and The F.B.I. vs. Apple – Aug 10
- ↳ Original Proposal – How The Other Half Banks: Exclusion, Exploitation, and The Threat To Democracy – July 13
- ↳ Participant Comments – San Bernardino and The F.B.I. vs. Apple – Aug 10
- ↳ Reference Materials – San Bernardino and The F.B.I. vs. Apple – Aug 10
- ↳ Reference Materials – How The Other Half Banks: Exclusion, Exploitation, and The Threat To Democracy – July 13
- ↳ Cancellation – How The Other Half Banks: Exclusion, Exploitation, and The Threat To Democracy – July 13
- ↳ Suggested Discussion Outline – 5 Easy Theses: Commonsense Solutions to America’s Greatest Economic Challenges – June 15
- ↳ Original Proposal – 5 Easy Theses: Commonsense Solutions to America’s Greatest Economic Challenges – June 15
- ↳ Participant Comments - 5 Easy Theses: Commonsense Solutions to America’s Greatest Economic Challenges – June 15
- ↳ Reference Materials – 5 Easy Theses: Commonsense Solutions to America’s Greatest Economic Challenges – June 15
- ↳ Suggested Discussion Outline – Evicted: Poverty and Profit in the American City – May 18
- ↳ Original Proposal – Evicted: Poverty and Profit in the American City – May 18
- ↳ Participant Comments – Evicted: Poverty and Profit in the American City – May 18
- ↳ Reference Materials – Evicted: Poverty and Profit in the American City – May 18
- ↳ Suggested Discussion Outline – Dark Money: The Hidden History of the Billionaires Behind the Rise of the Radical Right – April 20
- ↳ Original Proposal – Dark Money: The Hidden History of the Billionaires Behind the Rise of the Radical Right – April 20
- ↳ Participant Comments – Dark Money: The Hidden History of the Billionaires Behind the Rise of the Radical Right – April 20
- ↳ Reference Materials – Dark Money: The Hidden History of the Billionaires Behind the Rise of the Radical Right – April 20
- ↳ Suggested Discussion Outline - Just Mercy: A Story of Justice and Redemption – March 16
- ↳ Original Proposal - Just Mercy: A Story of Justice and Redemption – March 16
- ↳ Reference Materials - Just Mercy: A Story of Justice and Redemption – March 16
- ↳ Participant Comments – Just Mercy: A Story of Justice and Redemption – March 16
- ↳ Suggested Discussion Outline – Capitalism vs. The Climate – Feb 17
- ↳ Participant Comments – Capitalism vs. The Climate – Feb 17
- ↳ Original Proposal – Capitalism vs. The Climate – Feb 17
- ↳ Reference Materials - Capitalism vs. The Climate – Feb 17
- ↳ Suggested Discussion Outline – The Sixth Extinction: An Unnatural History – Jan 13
- ↳ Original Proposal – The Sixth Extinction: An Unnatural History – Jan 13
- ↳ Participant Comments – The Sixth Extinction: An Unnatural History – Jan 13
- ↳ Reference Materials – The Sixth Extinction: An Unnatural History – Jan 13
- ↳ Original Proposal – Saving Capitalism by Robert Reich – Dec 16
- ↳ Suggested Discussion Outline – Saving Capitalism by Robert Reich – Dec 16
- ↳ Participant Comments – Saving Capitalism by Robert Reich – Dec 16
- ↳ Reference Materials - Saving Capitalism by Robert Reich – Dec 16
- ↳ Suggested Discussion Outline - The Teacher Wars: A History of America's Most Embattled Profession - Nov 18
- ↳ Original Proposal - The Teacher Wars: A History of America's Most Embattled Profession - Nov 18
- ↳ Participant Comments - The Teacher Wars: A History of America's Most Embattled Profession - Nov 18
- ↳ Reference Materials - The Teacher Wars: A History of America's Most Embattled Profession - Nov 18
- ↳ Suggested Discussion Outline - Phishing for Phools: The Economics of Manipulation and Deception by George Akerlof and Robert Shiller – Oct 14
- ↳ Original Proposal - Phishing for Phools: The Economics of Manipulation and Deception by George Akerlof and Robert Shiller – Oct 14
- ↳ Participant Comments - Phishing for Phools: The Economics of Manipulation and Deception by George Akerlof and Robert Shiller – Oct 14
- ↳ Reference Materials - Phishing for Phools: The Economics of Manipulation and Deception by George Akerlof and Robert Shiller – Oct 14
- ↳ Suggested Discussion Outline - The Impending Adverse Impact Of New Technology on Employment and Income Inequality – Sep 9th
- ↳ Original Proposal - The Impending Adverse Impact Of New Technology on Employment and Income Inequality – Sep 9th
- ↳ Participant Comments - The Impending Adverse Impact Of New Technology on Employment and Income Inequality – Sep 9th
- ↳ Reference Materials - The Impending Adverse Impact Of New Technology on Employment and Income Inequality – Sep 9th
- ↳ Suggested Discussion Outline – Joan Walsh’s “What’s the Matter with White People?” – Aug 12
- ↳ Original Proposal – Joan Walsh’s “What’s the Matter with White People?” – Aug 12
- ↳ Participant Comments – Joan Walsh’s “What’s the Matter with White People?” – Aug 12
- ↳ Reference Materials – Joan Walsh’s “What’s the Matter with White People?” – Aug 12
- ↳ Suggested Discussion Outline – The Lonely War: One Woman’s Account of the Struggle for Modern Iran – July 15
- ↳ Original Proposal – The Lonely War: One Woman’s Account of the Struggle for Modern Iran – July 15
- ↳ Participant Comments – The Lonely War: One Woman’s Account of the Struggle for Modern Iran – July 15
- ↳ Reference Materials – The Lonely War: One Woman’s Account of the Struggle for Modern Iran – July 15
- ↳ CALL TO ACTION – "SIX-DEGREES-OF-SEPARATION" E-MAIL CAMPAIGN – POPE FRANCIS AND 23% OF U.S. CHILDREN IN POVERTY
- ↳ Suggested Discussion Outline - The Hoax of the School-Privatization Movement - June 17
- ↳ Original Proposal - The Hoax of the School-Privatization Movement - June 17
- ↳ Suggested Discussion Outline - Why Foreign-Government Corruption Threatens Global Security – May 13
- ↳ Participant Comments - The Hoax of the School-Privatization Movement - June 17……………………………………… AMERICA’S APARTHEID “JUSTICE” SYSTEM -- BALTIMORE, AMERICAN INNER-CITIES AND TOM BRADY
- ↳ Original Proposal - Why Foreign-Government Corruption Threatens Global Security – May 13
- ↳ Reference Materials - The Hoax of the School-Privatization Movement - June 17
- ↳ Participant Comments - Why Foreign-Government Corruption Threatens Global Security – May 13
- ↳ Reference Materials - Why Foreign-Government Corruption Threatens Global Security – May 13
- ↳ Suggested Discussion Outline - Corruption in America - April 8
- ↳ Original Proposal - Corruption in America – April 8
- ↳ Participant Comments - Corruption in America – April 8
- ↳ Reference Materials - Corruption in America – April 8
- ↳ Suggested Discussion Outline - Leon Panetta’s Worthy Fights and President Obama’s Military Force Authorization - March 11
- ↳ Original Proposal - Leon Panetta’s Worthy Fights and President Obama’s Military Force Authorization - March 11
- ↳ Original Proposal - Losing Our Way: An Intimate Portrait of a Troubled America - Feb 11
- ↳ Participant Comments - Leon Panetta’s Worthy Fights and President Obama’s Military Force Authorization - March 11
- ↳ Reference Materials - Leon Panetta’s Worthy Fights and President Obama’s Military Force Authorization - March 11
- ↳ Suggested Discussion Outline - Losing Our Way: An Intimate Portraith of a Troubled America - Feb 11
- ↳ Participant Comments - Losing Our Way: An Intimate Portrait of a Troubled America – Feb 11
- ↳ Reference Materials - Losing Our Way: An Intimate Portrait of a Troubled America – Feb 11
- ↳ Suggested Discussion Outline - Hillary Distancing Herself From Pres. Obama Re The Islamic State - For Sep 3
- ↳ Original Proposal - Hillary Distancing Herself From Pres. Obama Re The Islamic State - For Sep 3
- ↳ Participant Comments - Hillary Distancing Herself From Pres. Obama Re The Islamic State - For Sep 3
- ↳ Reference Materials - Hillary Distancing Herself From Pres. Obama Re The Islamic State - For Sep 3
- ↳ Original Proposal - American Exceptionalism: Fact or Fiction??? - Aug 6th
- ↳ Participant Comments - American Exceptionalism: Fact or Fiction??? - Aug 6th
- ↳ MEETING CANCELLATION + SABBATICAL
- ↳ MEETING CANCELLATION + SABBATICAL (Continued)
- ↳ Original Proposal - The Hoax of the School-Privatization Movement - May 7th
- ↳ Suggested Discussion Outline -- NUCLEAR FUSION AND 50 MORE YEARS WANDERING IN THE WILDERNESS SHUNNING THE PROMISED LAND -- Apr 9th
- ↳ Do-It-Yourself-Six-Degrees-Of-Separation-Email-Campaign -- Nuclear Fusion and 50 More Years Wandering in the Wilderness Shunning the Promised Land
- ↳ Participant Comments -- Nuclear Fusion and 50 More Years Wandering in the Wilderness Shunning the Promised Land -- April 9th
- ↳ Reference Materials -- Nuclear Fusion and 50 More Years Wandering in the Wilderness Shunning the Promised Land -- April 9th
- ↳ Original Proposal -- Nuclear Fusion and 50 More Years Wandering in the Wilderness Shunning the Promised Land -- April 9th
- ↳ Suggested Discussion Outline - Angry White Men: American Masculinity at the End of an Era – March 12th
- ↳ Original Proposal - Angry White Men: American Masculinity at the End of an Era – March 12th
- ↳ Participant Comments - Angry White Men: American Masculinity at the End of an Era – March 12th
- ↳ Reference Materials - Angry White Men: American Masculinity at the End of an Era – March 12th
- ↳ CALL TO ACTION – "SIX-DEGREES-OF-SEPARATION" E-MAIL CAMPAIGN TO PRESIDENT OBAMA – RENEWING 1968 EXECUTIVE ORDER 11387 TO HALT THE EXPORT OF AMERICAN JOBS
- ↳ Discussion Outline – 12 Years A Slave, the 1853 autobiography of a free black man who was kidnapped in Washington DC in 1841 and sold into slavery, which became a famous part of the Abolitionist Movement – Feb 12th
- ↳ Original Proposal – 12 Years A Slave, the 1853 autobiography of a free black man who was kidnapped in Washington DC in 1841 and sold into slavery, which became a famous part of the Abolitionist Movement – Feb 12th
- ↳ Participant Comments – 12 Years A Slave, the 1853 autobiography of a free black man who was kidnapped in Washington DC in 1841 and sold into slavery, which became a famous part of the Abolitionist Movement – Feb 12th
- ↳ Reference Materials – 12 Years A Slave, the 1853 autobiography of a free black man who was kidnapped in Washington DC in 1841 and sold into slavery, which became a famous part of the Abolitionist Movement – Feb 12th
- ↳ Discussion Outline - Magnificent Delusions: Pakistan, the U.S., and An Epic History of Misunderstanding – Jan 8th
- ↳ Original Proposal - Magnificent Delusions: Pakistan, the U.S., and An Epic History of Misunderstanding – Jan 8th
- ↳ Participant Comments - Magnificent Delusions: Pakistan, the U.S., and An Epic History of Misunderstanding – Jan 8th
- ↳ Reference Materials - Magnificent Delusions: Pakistan, the U.S., and An Epic History of Misunderstanding – Jan 8th
- ↳ Suggested Discussion Outline – Third-Trimester Abortions – Dec. 11th
- ↳ Original Proposal – Third-Trimester Abortions – Dec. 11th
- ↳ Participant Comments – Third-Trimester Abortions – Dec. 11th
- ↳ Reference Materials – Third-Trimester Abortions – Dec. 11th
- ↳ Discussion Outline - Will Ayatollah Khomenei Destroy The World??? - Nov 13
- ↳ Original Proposal - Who Is Ayatollah Khamenei by an Iranian Journalist/Dissident - Nov 13
- ↳ Participant Comments - Who Is Ayatollah Khamenei by an Iranian Journalist/Dissident - Nov 13
- ↳ Reference Materials - Who Is Ayatollah Khamenei by an Iranian Journalist/Dissident - Nov 13
- ↳ Discussion Outline - Austerity: The History of a Dangerous Idea - Oct 9th
- ↳ Original Proposal - Austerity: The History of a Dangerous Idea - Oct 9th
- ↳ Participant Comments - Austerity: The History of a Dangerous Idea - Oct 9th
- ↳ Reference Materials - Austerity: The History of a Dangerous Idea - Oct 9th
- ↳ CALL TO ACTION - SIX-DEGREES-OF-SEPARATION E-MAIL CAMPAIGN TO PRESIDENT OBAMA REGARDING THE DEVELOPMENT OF THORIUM AS THE GREEN ENERGY SOURCE FOR THE FUTURE WHICH WILL, INTER ALIA, SOLVE OCEANIC ACIDIFICATION
- ↳ CALL TO ACTION - SIX-DEGREES-OF-SEPARATION E-MAIL CAMPAIGN TO PRESIDENT OBAMA REGARDING THE ENFORCEMENT OF OCEAN CONSERVATION
- ↳ Discussion Outline - Oceana by Ted Danson - Sep 11
- ↳ Original Proposal - Oceana by Ted Danson - Sep 11
- ↳ Participant Comments - Oceana by Ted Danson - Sep 11
- ↳ Reference Materials - Oceana by Ted Danson - Sep 11
- ↳ Discussion Outline - Our Current House-Of-Cards National Banking System - Aug 14
- ↳ Original Proposal - Our Current House-Of-Cards National Banking System - Aug 14
- ↳ Participant Comments - Our Current House-Of-Cards National Banking System - Aug 14
- ↳ ELLEN BIRRELL & JIM HUTCHINS – RSVP’S FOR AUG 14
- ↳ Reference Materials - Our Current House-Of-Cards National Banking System - Aug 14
- ↳ Discussion Outline - The Thistle and The Drone - July 10th
- ↳ Original Proposal - The Thistle and The Drone - July 10th
- ↳ Participant Comments - The Thistle and The Drone - July 10th
- ↳ Reference Materials - The Thistle and The Drone - July 10th
- ↳ Meeting Cancellation - The New Digital Age by Google's Eric Schmidt & Jared Cohen - June 12th
- ↳ Original Proposal - The New Digital Age by Google's Eric Schmidt & Jared Cohen - June 12th
- ↳ Participant Comments - The New Digital Age by Google's Eric Schmidt & Jared Cohen - June 12th
- ↳ Reference Materials - The New Digital Age by Google's Eric Schmidt & Jared Cohen - June 12th
- ↳ Discussion Outline - Federal Bailouts of Illinois and Detroit, Etc., Etc., Etc. - May 8th
- ↳ Original Proposal - Federal Bailouts of Illinois and Detroit, Etc., Etc., Etc. - May 8th
- ↳ Participant Comments - Federal Bailouts of Illinois and Detroit, Etc., Etc., Etc. – May 8th
- ↳ Discussion Outline - Salt-Sugar-Fat: How The Food Giants Hooked Us – April 10th
- ↳ Reference Materials - Federal Bailouts of Illinois and Detroit, Etc., Etc., Etc. – May 8th
- ↳ Original Proposal - Salt-Sugar-Fat: How The Food Giants Hooked Us – April 10th
- ↳ Participant Comments – Salt-Sugar-Fat: How The Food Giants Hooked Us – April 10th
- ↳ Reference Materials – Salt-Sugar-Fat: How The Food Giants Hooked Us – April 10th
- ↳ UNOFFICIAL SIX-DEGREES-OF-SEPARATION E-MAIL CAMPAIGN TO PRESIDENT OBAMA REGARDING ANNUAL DEFICITS AND ACCUMULATED DEBT
- ↳ Discussion Outline - How To Regain America's Competitive Edge And Boost Our Global Standing - March 13th
- ↳ Original Proposal – How To Regain America’s Competitive Edge And Boost Our Global Standing – March 13th
- ↳ Participant Comments - How To Regain America’s Competitive Edge And Boost Our Global Standing – March 13th
- ↳ Reference Materials - How To Regain America’s Competitive Edge And Boost Our Global Standing – March 13th
- ↳ Discussion Outline - John Brennan's Nomination To Head The CIA - Feb 6th
- ↳ Original Proposal - John Brennan's Nomination To Head The CIA - Feb 6th
- ↳ Participant Comments - John Brennan's Nomination To Head The CIA - Feb 6th
- ↳ Reference Materials - John Brennan's Nomination To Head The CIA - Feb 6th
- ↳ Discussion Outline - Assisted Suicide - Jan 9th
- ↳ Original Proposal - Assisted Suicide - Jan 9th
- ↳ Participant Comments - Assisted Suicide - Jan 9th
- ↳ Reference Materials - Assisted Suicide - Jan 9th
- ↳ Discussion Outline - It's Even Worse Than It Looks by Mann + Ornstein - Dec 12th
- ↳ Original Proposal - It's Even Worse Than It Looks By Mann + Ornstein - Dec 12th
- ↳ Participant Comments - It's Even Worse Than It Looks By Mann + Ornstein - Dec 12th
- ↳ Reference Materials - It's Even Worse Than It Looks By Mann + Ornstein - Dec 12th
- ↳ SIX-DEGREES-OF-SEPARATION E-MAIL CAMPAIGN TO PRINCETON ECONOMICS NOBEL-LAUREATE PROF. AND NY TIMES OP-ED COLUMNIST PAUL KRUGMAN – YOUR HELP DESPERATELY NEEDED TO AVERT ANOTHER ECONOMIC MELTDOWN - ONLY 5 MINUTES NEEDED TO PARTICIPATE
- ↳ Discussion Outline - The Price of Inequality - Nov. 14th
- ↳ Original Proposal - The Price of Inequality - November 14th
- ↳ Participant Comments - The Price of Inequality - November 14th
- ↳ Reference Materials - The Price of Inequality - November 14th
- ↳ SIX-DEGREES-OF-SEPARATION E-MAIL CAMPAIGN TO D.O.E. SECRETARY CHU – R&D FOR THORIUM, THE GREEN ENERGY SOURCE FOR THE FUTURE - ONLY 5 MINUTES NEEDED TO PARTICIPATE
- ↳ Discussion Outline - Thorium: The Green Energy Source For The Future – October 10th
- ↳ Original Proposal – Thorium: The Green Energy Source For The Future – October 10th
- ↳ Participant Comments - Thorium: The Green Energy Source For The Future – October 10th
- ↳ SIX-DEGREES-OF-SEPARATION E-MAIL CAMPAIGN FOR PROSECUTION OF BILL AND MELINDA GATES AT THE INTERNATIONAL CRIMINAL COURT FOR "CRIMES AGAINST HUMANITY" (only 5 minutes needed to participate)
- ↳ Reference Materials - Thorium: The Green Energy Source For The Future – October 10th
- ↳ Discussion Outline – DOES CALLING A RATTLESNAKE A CANARY SOLVE THE PROBLEM IF THE “CANARY” BITES YOU??? – September 12th
- ↳ Original Proposal - Gates Foundation Crimes Against US Education Policy – September 12th
- ↳ Reference Materials - Gates Foundation Crimes Against US Education Policy – September 12th
- ↳ Participant Comments - Gates Foundation Crimes Against US Education Policy – September 12th
- ↳ Discussion Outline - Winner-Take-All-Politics – August 8th
- ↳ Original Proposal – Winner-Take-All-Politics – August 8th
- ↳ Participant Comments – Winner-Take-All-Politics – August 8th
- ↳ Reference Materials – Winner-Take-All-Politics – August 8th
- ↳ Discussion Outline - Gates Foundation's "Crimes Against Humanity" - July 11th
- ↳ Original Proposal - Thinking, Fast and Slow by Daniel Kahneman - July 11th
- ↳ Participant Comments - Thinking, Fast and Slow by Daniel Kahneman - July 11th
- ↳ Reference Materials - Thinking, Fast and Slow by Daniel Kahneman - July 11th
- ↳ Discussion Outline - How Invisible Policies Undermine American Democracy - June 13th
- ↳ Original Proposal - How Invisible Governmental Policies Undermine American Democracy - June 13th
- ↳ Participant Comments - How Invisible Governmental Policies Undermine American Democracy - June 13th
- ↳ Discussion Outline -- Merchants of Doubt -- May 9th
- ↳ Reference Materials - How Invisible Governmental Policies Undermine American Democracy - June 13th
- ↳ Participant Comments -- Merchants of Doubt -- May 9th
- ↳ Original Proposal -- Merchants of Doubt -- May 9th
- ↳ Reference Materials - Merchants of Doubt - May 9th
- ↳ Discussion Outline -- The Gardens of Democracy: A New American Story of Citizenship, the Economy, and the Role of Government -- April 11th
- ↳ Original Proposal -- The Gardens of Democracy: A New American Story of Citizenship, the Economy, and the Role of Government -- April 11th
- ↳ Participant Comments -- The Gardens of Democracy: A New American Story of Citizenship, the Economy, and the Role of Government -- April 11th
- ↳ Reference Materials -- The Gardens of Democracy: A New American Story of Citizenship, the Economy, and the Role of Government -- April 11th
- ↳ Discussion Outline - Insight Into Life In North Korea - The Orphan Master's Son by Prof. Adam Johnson - March 14th
- ↳ Original Proposal - Insight Into Life In North Korea - The Orphan Master's Son by Prof. Adam Johnson - March 14th
- ↳ Participant Comments - Insight Into Life In North Korea - The Orphan Master's Son by Prof. Adam Johnson - March 14th
- ↳ Reference Materials - Insight Into Life In North Korea - The Orphan Master's Son by Prof. Adam Johnson - March 14th
- ↳ Discussion Outline – Real Politik (aka National Interest) and Libya vs. Iran -- Feb 8th
- ↳ Original Proposal -- Real Politik (aka National Interest) and Libya vs. Iran -- Feb 8th
- ↳ Participant Comments -- Real Politik (aka National Interest) and Libya vs. Iran -- Feb 8th
- ↳ Reference Materials -- Real Politik (aka National Interest) and Libya vs. Iran -- Feb 8th
- ↳ Discussion Outline - All The Devils Are Here: The Hidden History Of The Financial Crisis - Jan 11th
- ↳ Original Proposal - All The Devils Are Here: The Hidden History Of The Financial Crisis - Jan11
- ↳ Participant Comments - All The Devils Are Here: The Hidden History Of The Financial Crisis - Jan 11
- ↳ Reference Materials - All The Devils Are Here: The Hidden History Of The Financial Crisis - Jan 11
- ↳ CALL TO ACTION -- "SIX-DEGREES-OF-SEPARATION" E-MAIL CAMPAIGN = TRillions Being Printed To Bail Out Foreign Banks and Governments -- (ONLY 5 MINUTES NEEDED TO PARTICIPATE)
- ↳ Discussion Outline - Balanced-Budget Amendments & Redeeming National Debt With “Wallpaper” In Both Europe and the U.S. - December 14th
- ↳ Original Proposal - Balanced-Budget Amendments & Redeeming National Debt With “Wallpaper” In Both Europe and the U.S. - December 14th
- ↳ Participant Comments - Balanced-Budget Amendments & Redeeming National Debt With “Wallpaper” In Both Europe and the U.S. - December 14th
- ↳ Reference Materials - Balanced-Budget Amendments & Redeeming National Debt With “Wallpaper” In Both Europe and the U.S. - December 14th
- ↳ CALL TO ACTION -- "SIX-DEGREES-OF-SEPARATION" E-MAIL CAMPAIGN = Benefiting American Taxpayers For The Scientific Discoveries Of Basic Research They Have Financed -- (ONLY 5 MINUTES NEEDED TO PARTICIPATE)
- ↳ Discussion Outline - That Used To Be Us By Thomas Friedman - Nov 9th
- ↳ Participant Comments - That Used To Be Us By Thomas Friedman - Nov 9th
- ↳ Original Proposal - That Used To Be Us By Thomas Friedman - Nov 9th
- ↳ Reference Materials - That Used To Be Us By Thomas Friedman - Nov 9th
- ↳ Discussion Outline - Can The Middle Class Be Saved - Oct 12th
- ↳ Original Proposal - Can The Middle Class Be Saved? - Oct 12th
- ↳ Participant Comments - Can The Middle Class Be Saved - Oct 12th
- ↳ Reference Materials - Can The Middle Class Be Saved? - Oct 12th
- ↳ Suggested Discussion Outline - Even Silence Has An End by Ingrid Betencourt - Sep 14th
- ↳ Original Proposal - Even Silence Has An End by Ingrid Betencourt - Sep 14th
- ↳ Participant Comments - Even Silence Has An End by Ingrid Betancourt - Sep 14th
- ↳ Reference Materials - Even Silence Has An End by Ingrid Betancourt - Sep 14th
- ↳ Discussion Outline - Blood Brothers by Elias Chacour - August 10th
- ↳ Original Proposal – Blood Brothers by Elias Chacour – August 10th
- ↳ Participant Comments - Blood Brothers by Elias Chacour - August 10th
- ↳ Reference Materials - Blood Brothers by Elias Chacour - August 10th
- ↳ Discussion Outline - America's Climate Problem, The Way Forward - July 13th
- ↳ Original Proposal - America's Climate Problem, The Way Forward - July 13th
- ↳ Participant Comments - America's Climate Problem, The Way Forward - July 13th
- ↳ Reference Materials - America's Climate Problem, The Way Forward - July 13th
- ↳ Post-Meeting Discussion - Monsoon: The Indian Ocean and the Future of American Power - June 15th
- ↳ Discussion Outline - Monsoon: The Indian Ocean and the Future of American Power - June 15th
- ↳ Original Proposal - Monsoon: The Indian Ocean and the Future of American Power - June 15th
- ↳ DO-IT-YOURSELF SIX-DEGREES-OF-SEPARATION-E-MAIL-CAMPAIGN = Insuring The Survival Of The Democratic Party Following A Nuclear Attack On The U.S. By Terrorists - ONLY-5-MINUTES-REQUIRED-TO-PARTICIPATE
- ↳ Participant Comments - Monsoon: The Indian Ocean and the Future of American Power - June 15th
- ↳ Reference Materials - Monsoon: The Indian Ocean and the Future of American Power - June 15th
- ↳ SIX-DEGREES-OF-SEPARATION-E-MAIL-CAMPAIGNS = Taxing-Corporate-Profits-From-Exporting-American-Jobs + Benefitting-American-Taxpayers-For-The-Scientific-Discoveries-Of-Basic-Research-They-Have-Financed - ONLY-5-MINUTES-REQUIRED-TO-PARTICIPATE
- ↳ Discussion Outline - Debtor Nation: The History Of America In Red Ink - May 11th
- ↳ Original Proposal - Debtor Nation: The History Of America In Red Ink - for May 11th
- ↳ Participant Comments - Debtor Nation: The History Of America In Red Ink - for May 11th
- ↳ Reference Materials - Debtor Nation: The History of America in Red Ink - for May 11th
- ↳ DO-IT-YOURSELF SIX-DEGREES-OF-SEPARATION E-MAIL CAMPAIGN – Apr.13th
- ↳ Discussion Outline - President Obama’s Nuclear Stand Post-Japan - April 13th
- ↳ Participant Comments - President Obama’s Nuclear Stand Post-Japan - April 13th
- ↳ Original Proposal - President Obama’s Nuclear Stand Post-Japan - April 13th
- ↳ Reference Materials - President Obama’s Nuclear Stand Post-Japan - April 13th
- ↳ Discussion Outline - Religious Freedom And National Security - Mar 16th
- ↳ Original Proposal - Religious Freedom And National Security - Mar 16th
- ↳ Participant Comments - Religious Freedom And National Security - Mar 16th
- ↳ Reference Materials - Religious Freedom And National Security - Mar 16th
- ↳ DO-IT-YOURSELF SIX-DEGREES-OF-SEPARATION E-MAIL CAMPAIGN – Feb 9th
- ↳ Discussion Outline - Reports By Two Deficit-Reduction Commissions - Feb 9
- ↳ Original Proposal - Reports By Two Deficit-Reduction Commissions - Feb 9
- ↳ Participant Comments - Reports By Two Deficit-Reduction Commissions - Feb 9
- ↳ Reference Materials - Reports By Two Deficit-Reduction Commissions - Feb 9
- ↳ Discussion Outline - Making Our Democracy Work by US Supreme Ct Justice Stephen Breyer - Jan 12th
- ↳ Original Proposal - Making Our Democracy Work by US Supreme Ct Justice Stephen Breyer - Jan 12th
- ↳ Post-Meeting Participant Comments - Making Our Democracy Work by US Supreme Ct Justice Stephen Breyer - Jan 12th
- ↳ Participant Comments - Making Our Democracy Work by US Supreme Ct Justice Stephen Breyer - Jan 12th
- ↳ Reference Materials - Making Our Democracy Work by US Supreme Ct Justice Stephen Breyer - Jan 12th
- ↳ Discussion Outline - The US Gov's "Kill List" To Assassinate US Citizens in Yemen - Dec 15th
- ↳ Original Proposal - The US Gov's "Kill List" To Assassinate US Citizens in Yemen - Dec 15th
- ↳ Participant Comments - The US Gov's "Kill List" To Assassinate US Citizens in Yemen - Dec 15th
- ↳ Reference Materials - The US Gov's "Kill List" To Assassinate US Citizens in Yemen - Dec 15th
- ↳ Unofficial Six-Degrees-Of-Separation E-mail Campaign - Obama's Wars - Nov. 10th
- ↳ Original Proposal - Obama's Wars by Bob Woodward - Nov 10th
- ↳ Participant Comments - Obama's Wars by Bob Woodward - Nov 10th
- ↳ Reference Materials - Obama's Wars by Bob Woodward - Nov. 10th
- ↳ Discussion Outline -- Murder City – What Does Juarez say about our future? -- Oct 13th
- ↳ Original Proposal - MurderCity - What does Juarez say about our future? - Oct 13th
- ↳ Participant Comments - MurderCity: What does Juarez say about our future? - Oct 13th
- ↳ Reference Materials - MurderCity: What does Juarez say about our future? - Oct 13th
- ↳ Discussion Outline - - The Big Sort: Why The Clustering Of Like-Minded America Is Tearing Us Apart - Sep. 15th
- ↳ Original Proposal - The Big Sort: Why The Clustering Of Like-Minded America Is Tearing Us Apart - Sep. 15th
- ↳ Participant Comments - The Big Sort: Why The Clustering Of Like-Minded America Is Tearing Us Apart - Sep. 15th
- ↳ Reference Materials - The Big Sort: Why The Clustering Of Like-Minded America Is Tearing Us Apart - Sep. 15th
- ↳ Suggested Discussion Outline - Greg Mortenson's Stones Into Schools: Promoting Peace With Books, Not Bombs, In Afghanistan and Pakistan - August 11th
- ↳ Original Proposal - Greg Mortenson's Stones Into Schools: Promoting Peace With Books, Not Bombs, In Afghanistan and Pakistan - August 11th
- ↳ Participant Comments - Greg Mortenson's Stones Into Schools: Promoting Peace With Books, Not Bombs, In Afghanistan and Pakistan - August 11th
- ↳ Reference Materials - Greg Mortenson's Stones Into Schools: Promoting Peace With Books, Not Bombs, In Afghanistan and Pakistan - August 11th
- ↳ Suggested Discussion Outline - The Broken Branch: How Congress Is Failing America And How To Get It Back - July 14th
- ↳ Original Proposal - The Broken Branch: How Congress Is Failing America And How To Get It Back - July 14th
- ↳ Participant Comments - "The Broken Branch: How Congress Is Failing America And How To Get It Back" - July 14th
- ↳ Reference Materials - The Broken Branch: How Congress Is Failing America and How To Get It Back - July 14th
- ↳ Suggested Discussion Outline - Arizona's New Immigration Law - June 9th
- ↳ Original Proposal - Arizona's New Immigration Law - June 9th
- ↳ Participant Comments - Arizona's New Immigration Law - June 9th
- ↳ Reference Materials - Arizona's New Immigration Law - June 9th
- ↳ Meeting Cancellation - After Iran Gets The Bomb (Foreign Affairs Magazine Lead Article) - May 12th
- ↳ Original Proposal - After Iran Gets The Bomb (Foreign Affairs Magazine Lead Article) - May 12th
- ↳ Participant Comments - After Iran Gets The Bomb (Foreign Affairs Magazine Lead Article) - May 12th
- ↳ Suggested Discussion Outline - "The Shock Doctrine: Rise of Disaster Capitalism" - April 14
- ↳ Reference Materials - After Iran Gets The Bomb (Foreign Affairs Magazine Lead Article) - May 12th
- ↳ Original Proposal - The Shock Doctrine: The Rise of Disaster Capitalism - April 14
- ↳ Participant Comments - "The Shock Doctrine: The Rise of Disaster Capitalism" - April 14
- ↳ Reference Materials - The Shock Doctrine: The Rise of Disaster Capitalism - April 14
- ↳ “SIX-DEGREES-OF-SEPARATION” CALL TO ACTION = The Supreme Court’s Recent Corporate-Campaign-Contribution Decision - (ONLY 5 MINUTES NEEDED TO PARTICIPATE)
- ↳ Suggested Discussion Outline - US Supreme Court 1/21/2010 Decision on Campaign Contributions by Corporations - March 10
- ↳ Original Proposal - U.S. Supreme Court 1/21/2010 Decision on Campaign Contributions by Corporations - March 10
- ↳ Participant Comments - U.S. Supreme Court 1/21/2010 Decision on Campaign Contributions by Corporations - March 10
- ↳ Reference Materials - U.S. Supreme Court 1/21/2010 Decision on Campaign Contributions by Corporations - March 10
- ↳ Suggested Discussion Outline - When China Rules The World - Feb 10th
- ↳ Original Proposal - Martin Jacques' "When China Rules The World" - Feb. 10th
- ↳ Reference Mats + Participant Comments - When China Rules the World - Feb 10th -- including Suggested Answers to the Short Quiz and the NY Times Book Review on "When China Rules The World"
- ↳ “SIX-DEGREES-OF-SEPARATION” CALL TO ACTION = The ONLY Way To Transform The Prevailing SINGLE-DIGIT Inner-City High School Graduation Rates to 65%-70% And Beyond - (ONLY 5 MINUTES NEEDED TO PARTICIPATE)
- ↳ Suggested Discussion Outline - Oprah Winfrey's "Precious" - Jan. 13th
- ↳ Original Proposal - Continuing Our Oprah Tradition With "Precious" – Jan 13th
- ↳ Participant Comments and Reference Materials - Continuing Our Oprah Tradition With “Precious” – Jan 13th
- ↳ “SIX-DEGREES-OF-SEPARATION” CALL TO ACTION = Eliminating Unemployment With A “National Security Work Force” (ONLY 5 MINUTES NEEDED TO PARTICIPATE)
- ↳ Original Proposal - Dorothy Kearns Goodwin's Pulitzer-Prize Winning "No Ordinary Time: Franklin and Eleanor Roosevelt: The Home Front in World War II" - Dec. 9
- ↳ Participant Comments and Reference Materials - Dorothy Kearns Goodwin's Pulitzer-Prize Winning "No Ordinary Time: Franklin and Eleanor Roosevelt: The Home Front in World War II" - Dec. 9
- ↳ "SIX DEGREES OF SEPARATION" CALL TO ACTION - General Motors & the EPA Perpetrating Fraud Re the Chevrolet Volt (ONLY 5 MINUTES NEEDED TO PARTICIPATE)
- ↳ Original Proposal - General Motors + the EPA Perpetrating Fraud Re the Chevrolet Volt - Nov 18
- ↳ Participant Comments - General Motors and the EPA Perpetrating Fraud Re the Chevrolet Volt - Nov 18
- ↳ Reference Materials – General Motors and the EPA Perpetrating Fraud Re the Chevrolet Volt – Nov 18
- ↳ CALL TO ACTION - "American Policy Toward Palestinians = The Key to Middle-East Peace" - ONLY 5 MINUTES NEEDED TO PARTICIPATE
- ↳ Original Proposal - American Policy Toward Israel - Oct 14th
- ↳ Participant Comments - American Policy Toward Israel - Oct 14th
- ↳ Reference Materials - American Policy Toward Israel - Oct 14th
- ↳ Suggested Discussion Outline - Health Care/Insurance Reform - Sep. 9th
- ↳ Bill Lee's Original Proposal - Health-Care (or Health-Insurance) Reform - Sep 9th
- ↳ Participant Comments - Health-Care (Health-Insurance) Reform - Sep 9th
- ↳ Reference Materials - Health-Care (Health-Insurance) Reform - Sep 9th
- ↳ Original Proposal - Three Cups of Tea - August 12th
- ↳ Participant Comments - "Three Cups of Tea" - Aug. 12th
- ↳ Suggested Discussion Outline - How to Change The World - July 8th
- ↳ Original Proposal - How To Change The World - July 8th
- ↳ Participant Comments - How To Change The World - July 8th
- ↳ Original Proposal - Come Home America - June 10
- ↳ Suggested Discussion Outline - Come Home America - June 10
- ↳ Reference Materials - How To Change The World - July 8th
- ↳ Participant Comments - Come Home America - June 10
- ↳ CALL TO ACTION - The ONLY Way To Transform SINGLE-DIGIT Inner-City High School Graduation Rates to 65%-70% - Only 5 Minutes Needed to Answer the Call to Action
- ↳ The Banking Imbroglio - Come Home America - June 10
- ↳ Reference Materials - Come Home America - June 10
- ↳ Suggested Discussion Outline - A Report Card for U.S. Education Secretary Arne Duncan - May 13
- ↳ Original Proposal - A Report Card for US Education Secretary Arne Duncan - May 13
- ↳ Participant Comments - A Report Card for US Education Secretary Arne Duncan - May 13
- ↳ Reference Materials - A Report Card for US Education Secretary Arne Duncan - May 13
- ↳ CALL TO ACTION – Human Intelligence vs. Surging in Afghanistan From 17,000 U.S. Troops to 70,000 and Beyond
- ↳ Suggested Discussion Outline - Afghanistan, President Obama's Vietnam and Pakistan, His Cambodia - April 8
- ↳ Original Proposal - Afghanistan, Pres. Obama's Vietnam and Pakistan, His Cambodia - April 8
- ↳ Participant Comments - Afghanistan, Pres. Obama's Vietnam and Pakistan, His Cambodia - April 8
- ↳ Reference Materials - Afghanistan, Pres. Obama's Vietnam and Pakistan, His Cambodia - April 8
- ↳ Suggested Discussion Outline - How Should Pres. Obama Reform Health Care - March 11
- ↳ Original Proposal - How Should Pres. Obama Reform Health Care - March 11
- ↳ Suggested Discussion Outline - Saving the Democratic Party from Extinction: Foreign Policy - Feb. 11
- ↳ Participant Comments - How Should Pres. Obama Reform Health Care - March 11
- ↳ Feb. 11 Topic = Saving the Democratic Party from Extinction - Foreign Policy
- ↳ Report of the 2007 Democratic Congress' Commission on the Prevention of WMD Proliferation and Terrorism - Feb. 11
- ↳ Participant Comments - Saving the Democratic Party from Extinction/Foreign Policy - Feb. 11
- ↳ Other Background Mats - Saving the Democratic Party from Extinction/Foreign Policy - Feb. 11
- ↳ CALL TO ACTION - Separate BUT UNEQUAL Public Schools
- ↳ Suggested Discussion Outline - Leaving Children Behind - Jan. 14
- ↳ January 14th Topic = Leaving Children Behind
- ↳ Background Mats + Participant Comments - Leaving Children Behind - Jan. 14
- ↳ Suggested Discussion Outline - "It's The Economy, Stupid" - Dec. 10th
- ↳ Text - 2007 Supreme Court Reversal of School Integration - Leaving Children Behind - Jan. 14
- ↳ December 10th Meeting = "It's The Economy, Stupid"
- ↳ Participant Comments - "It's The Economy, Stupid" - Dec. 10th
- ↳ Suggested Discussion Outline - Al Gore's Challenge to America - Nov. 12
- ↳ Reference Materials - "It's The Economy, Stupid" - Dec. 10th
- ↳ CALL TO ACTION - Al Gore's 10-Year Challenge to America
- ↳ Participant Comments - Al Gore's Challenge to America - for Nov. 12
- ↳ Additional Ref Materials - Al Gore's Challenge to America - for Nov. 12
- ↳ Text of Al Gore's July 17th Challenge To Re-Power America's Electricity Grid Within 10 Years - For Nov. 12
- ↳ To Go "Beyond The Call of Duty" - Info About Three Background Books - For Nov. 12
- ↳ Suggested Discussion Outline - Team of Rivals - Oct. 8
- ↳ Suggested Discussion Outline - Barack Obama's Bible - Sep 10
- ↳ Participant Comments - "Team of Rivals - Oct 8
- ↳ Participant Comments - "Barack Obama's Bible = Rules for Radicals" - Sep 10
- ↳ Ref Mats - "Barack Obama's Bible = Rules for Radicals" - Sep 10
- ↳ Suggested Discussion Outline - Aug 13
- ↳ Comments of Participants - Obama From Promise to Power - Aug 13
- ↳ Reference Mats - Obama From Promise to Power - Aug 13
- ↳ Suggested Discussion Outline - Everything About Oil - July 9th
- ↳ Comments of Participants - Everything About Oil - July 9th
- ↳ Reference Materials - Everything About Oil - July 9th
- ↳ Tim Russert Eulogies
- ↳ A Fine Mess: A Global Quest for a Simpler, Fairer, and More Efficient Tax System by T.R. Reid – Oct 4
- ↳ Reference Materials – Revisiting The Issue Of Charter Schools: Stanford University vs. Stanford’s Hoover Institution – Oct 13
- ↳ Original Proposal - Blood Money: Why the Powerful Turn a Blind Eye While China Kills Americans by Peter Schweizer - April 17
- ↳ July Meeting - Possible Topics (historical)
- ↳ Suggested Discussion Outline - "Infidel" - June 11
- ↳ “Infidel” by Ayaan Hirsi Ali – for June 11
- ↳ Comments of Participants - "Infidel" - June 11th
- ↳ Reference Materials - "Infidel" - June 11th
- ↳ Suggested Discussion Outline - Bush's Law - May 14
- ↳ Eric Lichtblau's “Bush’s Law: The Remaking of American Justice” – May 14
- ↳ Participant Comments - "Bush's Law" - May 14
- ↳ Reference Materials - "Bush's Law" - May 14
- ↳ Suggested Discussion Outline - Apr 9th
- ↳ Clone Rights: Involuntary Soldiers, Sex Slaves, Human "Lab Rats" Etc. - Apr 9
- ↳ Participant Comments/Ref Mats - Clone Rights for Apr 9
- ↳ Suggested Discussion Outline - Mar 13
- ↳ Critiques of Benezir Bhutto’s “Reconciliation: Islam, Democracy and the West” - Mar 13th
- ↳ Benazir Bhutto's "Reconciliation: Islam, Democracy and the West" - for Mar. 13
- ↳ Comments of Participants - Mar. 13
- ↳ Background Materials - Mar. 13
- ↳ DRINKing Liberally Presentation - Fri Eve Feb 29
- ↳ Suggested Discussion Outline - Feb 14th
- ↳ Proposed Solution to The Cesspool that is Washington DC - for Feb 14
- ↳ "The Best Gov Money Can Buy: Bribery and Extortion" - Text of Original Proposal for Feb 14
- ↳ Participant Comments - The Best Gov Money Can Buy: Bribery & Extortion - Feb 14th
- ↳ Illegal “Bribe” vs. “Legal” Campaign Contribution - Feb 14th
- ↳ Background Mats - The Best Gov Money Can Buy: Bribery & Extortion - Feb 14th
- ↳ Suggested Discussion Outline - Jan 10th
- ↳ Illegal Immigration = Topic for Jan 10th
- ↳ Participant Comments on Immigration - Jan 10th
- ↳ Leading Dem Candidates on Immigration - Jan 10
- ↳ Leading Rep Candidates on Immigration - Jan 10
- ↳ Reference Materials - Immigration - Jan 10
- ↳ Call to Action - Meeting Report for Dec 13th
- ↳ Suggested Discussion Outline - Dec 13th
- ↳ Hillary's Bashing Bush as "Soft on Iran" - for Dec 13
- ↳ Is War With Iran Inevitable??? - Topic for Dec 13
- ↳ Action v. Deterrance (+ Detente) - for Dec 13
- ↳ Bombing Syria 9/6/2007 Re Iran & N Korea - for Dec 13
- ↳ Participant Comments Re War With Iran - for Dec 13
- ↳ Suggested Discussion Outline - Nov 8th
- ↳ Ref Mats - Osama's Fatwa To Nuke 10 Million Americans - Dec 13
- ↳ The Controversy That Is Bill Cosby for Nov 8th
- ↳ The KKK - "All The Best People In Society Belonged" - for Nov. 8th
- ↳ Participant Comments - School Integration & The Jena Six - for Nov 8th
- ↳ Background Mats - School Integration & The Jena Six - for Nov 8th
- ↳ Suggested Discussion Outline - Oct 11th
- ↳ Participant Comments Re Global Warming for Oct 11th
- ↳ Suggested Background Materials Re Global Warming for Oct 11th
- ↳ Suggested Discussion Outline - Sep 6th
- ↳ Suggested Discussion Outline - Aug 2d
- ↳ Comments of Participants - Universal Health Care for Aug 2nd
- ↳ Suggested Background Materials on Universal Health Care for Aug. 2d
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