Podcasts about california no

La Era de Internet nos abrió miles de posibilidades. Básicamente para buscar pareja y fracasar en el intento ECDQEMSD podcast episodio 6022 Busco Pareja en Internet Conducen: El Pirata y El Sr. Lagartija https://canaltrans.com Noticias del Mundo: Terremoto en California - No fue el Big One - Daniel Noboa ganó las elecciones - Oposición denuncia fraude - Política argentina - Murió Mario Vargas Llosa - Militares a la frontera - Expedientes desclasificados - Los marcianos - Katy Perry al espacio Historias Desintegradas: El amor en bits - La cena de gala tapatía - Facebook parejas - Un cyber Cupido convincente - El chacaloso del amor - El tiempo verbal - Familia integrada y ensamblada - Algo curioso - Abrí una cadena - Los amigos sexys - Yo no fui - Un misterioso malentendido - Retorno triunfal a la soltería - El niño español - Día del Arte - Fiesta cívica en Tarija y más... En Caso De Que El Mundo Se Desintegre - Podcast no tiene publicidad, sponsors ni organizaciones que aporten para mantenerlo al aire. Solo el sistema cooperativo de los que aportan a través de las suscripciones hacen posible que todo esto siga siendo una realidad. Gracias Dragones Dorados!! NO AI: ECDQEMSD Podcast no utiliza ninguna inteligencia artificial de manera directa para su realización. Diseño, guionado, música, edición y voces son de  nuestra completa intervención humana.

FASTEST Way to Get Divorced in California – No Court Required!

@PBNLinks | Linktreewww.packfreshusa.com

Tell us whatcha' think! Send a text to us, here!This week's Monday Briefing covers significant issues in education, focusing on racial equality, parental rights, and legal challenges regarding curriculum content. It highlights a case of a teacher advocating against discrimination in California, the implications of a school board's stance on a controversial bill in Ohio, and a legal battle concerning parental rights in education related to LGBTQ+ content in Maryland.Affiliate ShoutoutName: Sasha SewardLocation: Garden Grove, CaliforniaRole: Local Affiliate LeaderSupport the showDONATE TODAY!www.ParentsRightsInEducation.com

Lisset y su colega Monse nos visitaron para darnos información de los muchos servicios que tienen accesibles para la comunidad. Desde apoyo para gente que necesita renovar su numero de ITIN para sus impuestos, hasta el servicio para mandar cosas a México. No se necesita un seguro social para empezar un negocio y ellas están ahí para proveer este servicio como parte de su negocio. (707) 971-5188. #california #sonomacounty #indocumentados #daca #dacamented #dacadreamers #migrantes #impuestos #familia --- Support this podcast: https://podcasters.spotify.com/pod/show/rafael-vazquez7/support

Top 15 States In The U.S. For Human Trafficking Human trafficking is far from being a curable disease of human society, even in developed and first world countries. This is also the case with the US, of course. Human trafficking in the US involves both inflow of foreign people in the country and the local population. According to the statistics of the National Human Trafficking Hotline and Polaris BFree Textline, more than 49,000 trafficking cases were reported during the last decade in the US. Of all types of human trafficking, sexual exploitation is number one also in the US. More precisely – out of more than 10,000 reported human trafficking cases in 2017, around 7,200 were for the purpose of sexual exploitation. But today we are not focusing on the type of human trafficking, but on the general statistics countrywide. We have done the research for the last year on the same issue, where we included some of the worst stats for human trafficking in 2018, which you can check out in our article on 12 Top States for Human Trafficking in 2018. Getting into more detail, concerning the top cities for human trafficking in 2018, there was no any reliable information on a worldwide level, but we did research which concerns US cities, and you can read more about this in 16 Top US Cities for Human Trafficking in 2019. Concerning the previous years, on the matter of the top US cities for human trafficking in 2017, there is a nice visual representation made by Polaris, showing the map of the cities and areas with the highest density of human trafficking for this year. As we can see, situations in the top 10 states for human trafficking in 2017, or already mentioned top states for human trafficking in 2018 do not differ dramatically, which also stands for this year's situation. This fact shows that the local government does not take enough effort in preventing human trafficking cases and that this is a very hard thing to fight since human trafficking is a very developed industry. International Labour Organization estimates that human trafficking is a $150 billion industry, of which $99 billion belongs to sexual exploitation. We used some statistics provided for the last year since there is still not enough relevant data for 2019. However, it seems that trends remain more or less the same concerning the issues of the top states for human trafficking. So, we used the statistic provided by the National Human Trafficking Hotline, where reported cases were counted. Unfortunately, the number of unreported ones is unknown, so the situation might look a bit different than what we currently know. As the top 10 states for human trafficking have kept their positions over years, the same situation was to be expected for 2019 and on. But, let's see if there have been any oscillations in the number of reported human trafficking cases recently between them, and which the new incomers are in the 15 top states for human trafficking in 2019: 15. Arizona - No. of reported cases: 96 Arizona is fighting against human trafficking actively. In September 2018, 24 people were arrested for being involved in the serious crime of child sex trafficking. 14. Virginia - No. of reported cases: 98 Being among the top states for human trafficking, Virginia takes this problem seriously – it is the 6th state in the country when it comes to solving human trafficking cases. 13. New Jersey - No. of reported cases: 98 Even though New Jersey now takes the 13th place compared to the 12th place last year, the number of human trafficking victims has actually risen from 83 to 98 reported cases. This is because of the alarming fact that human trafficking is on the rise in the US as well as in the world. 12. Washington - No. of reported cases: 99 Despite Washington being the first state to sign the law that criminalizes human trafficking, this state, unfortunately still has an alarming number of human trafficking cases. 11. North Carolina - No. of reported cases: 126 Human trafficking in North Carolina falls from the 8th to 11th position from 2018 to 2019. That is a good thing, even though it is still among the states which have a very developed human trafficking industry. 10. Pennsylvania - No. of reported cases: 127 Although the rate of human trafficking in Pennsylvania is slowly decreasing, it is still among the top 10 states for human trafficking in 2019. 9. Illinois - No. of reported cases: 135 Illinois has risen one place higher comparing to 2018 when it was number ten, and still being among the top states for human trafficking in 2019. 8. Georgia - No. of reported cases: 157 It seems that human trafficking in Georgia has decreased, from the 6th place in 2018, it takes the 8th now. We hope it will continue to follow this path. 7. Nevada - No. of reported cases: 169 In Nevada, as in other states, sex trafficking is at the top. And it usually concerns girls younger than 18 years of age! 6. Michigan - No. of reported cases: 176 Good news came from Michigan the last October when 120 children who were victims of human trafficking were rescued. But this also shows the alarming fact that children are most endangered when it comes to human trafficking in the US. 5. New York - No. of reported cases: 206 It seems that the number of human trafficking (and especially sex trafficking) cases in New York is dramatically increasing. The number of 206 cases is more than double than during 2016, so we might expect that New York gets even a higher position if we are to conduct the research about the top states for human trafficking in 2019, again at the end of this year. 4. Ohio - No. of reported cases: 219 In Ohio,  the most trafficking take place in hotels and motels, Commercial-Front Brothels and online ad. venues, and it is mostly concentrated in the central part of the state. 3. Florida - No. of reported cases: 367 The government of Florida seems to be working hard on preventing human trafficking, even though the state is one among those that have the most human trafficking reported cases. Namely, during 2018, 277 people were arrested for sex trafficking during an undercover operation called “Operation No Trick, No Treats”. 2. Texas - No. of reported cases: 455 Human trafficking is crawling into every sphere of society it seems. News from Texas reported that an eighth-grade teacher was arrested in an attempt to traffic a child to Morocco. 1. California - No. of reported cases: 760 California seems to keep the first place in 15 top states for human trafficking in 2019 as well. Not only it precedes every other country but the number of reported cases is quite higher compared to the second top trafficking state, Texas, as we have seen. One of the main risk factors for human trafficking in California include migration and relocation, where Latinos and Asians are the main target groups. The Connection Between Foster Care and Human Trafficking The child welfare system is an important and necessary institution that protects children whose parents are unable to care for them. The overwhelming majority of children and youth in foster care placements and group homes are healthy and safe. However, it is undeniable that most children and youth who are victims of commercial sexual exploitation have been involved with the foster care system at one point in their lives. Commercially Sexually Exploited Children by State Minimally half of the commercially sexually exploited children on the streets today were at one time living in foster care or a group home run by the state. While most of reports place this number above 50 percent, the statistics widely vary. At the high end, Commissioner of the Connecticut Department of Children and Families, the Honorable Joette Katz, stated in her testimony to the state that in Connecticut, 98 percent of children who are identified as survivors of sex trafficking had previous involvement with child welfare services, and many were legally in the care and custody of the Connecticut Department of Children and Families while they were being prostituted by traffickers. Another study found that at least 85 percent of all CSEC in New York State had a child welfare background. On the statistical low end is the state of California that reported 50 percent of children sold in California are foster care children. While the statistics may vary by report, state and city, the overwhelming evidence suggests that the foster care system is a breeding ground for CSEC. Connection Between Foster Care Children and Commercially Sexually Exploited Children There are three childhood experiences that victims of CSE commonly share: prior sexual abuse by a family member or family friend; parental neglect or abandonment; or time spent as runaways or throwaways. Sexual abuse in particular is cited as a leading cause for entry into CSE, an estimated 65-95 percent of sex trafficking victims were sexually assaulted as children and 75 percent of all sex trafficking victims were at one point homeless. Children and youth are put in foster care placements or group homes when their parents are absent or can no longer adequately take care of them, leaving them prone to feelings of abandonment. There are a variety of reasons why the child welfare system takes children into custody, but the most common are parental substance abuse, alcohol abuse, domestic violence or neglect. A childhood of abuse and neglect greatly increases the chances for children to be lured into commercial sexual exploitation. It is also what runaway, throwaway and foster care children have in common. When asked, “What is the typical victim [of CSE] you come across?” FBI Agent and leader of the Tampa Area Crimes Against Children task force Gregory Christopher said, “A lot of these kids are foster kids, runaway kids… I'd say about 70 percent or so are foster kids. We work closely with DCF (Department of Children and Families).” Children and youth in the foster care system and those that run away from child protective services are more likely to become victims of CSE. The themes of childhood trauma, abandonment, and disruption are central to the stories of adolescents trafficked into commercial sexual exploitation. Without families to work on their behalf, it's much more difficult to rescue foster youths from sex trafficking and keep them out of the cycle.

CRITICAL, CURRENT ARTICLES RAT-A-TAT-TAT PRESIDENTIAL 2024 CHINA OUR ENEMY CLIMATE CHANGE CONSTITUTION CORRUPTION ECONOMY ELECTION FRAUD FAMILY SAFETY FINANCIAL & PHYSICAL PREPAREDNESS GLOBALISM GUN CONTROL IMMIGRATION INTERNATIONAL MEDIA MESS MILITARY OBAMA PSYOPS RINO WATCH TERROR TREASON WOKE WOMEN CRITICAL, CURRENT VIDEOS The post The Collapse Of Civilizations/History Part One-Destruction Of Unity….Have Property In California?  No Insurance For You…Wyoming (And Every Red State) –Listen To The People…..RFK's VP Pick–Progressive Left All The Way….Francis Scott Key Bridge–Maybe Not An Accident appeared first on On the Right Side Radio.

Issue(s): Whether a building-permit exaction is exempt from the unconstitutional-conditions doctrine as applied in Nollan v. California Coastal Commission and Dolan v. City of Tigard, Oregon simply because it is authorized by legislation.  ★ Support this podcast on Patreon ★

In today's episode Bob goes crazy with the new decision for California to eliminate emissions from locomotive trains.Are you trying to turn your state into a 3rd world country?To learn more, visit:https://www.terrafirmaconsultant.com/Listen to more episodes on Mission Matters:https://missionmatters.com/author/robert-wolf/

In a long-awaited action Wednesday, the EPA finalized its Renewable Fuel Standard (RFS) program establishing biofuel volume requirements for 2023 to 2025. However, the finalized program veered from the proposal the agency unveiled late last year which would have implemented a new credit system to incentivize EV manufacturing and purchasing. Over the past week, the average cost of regular unleaded in Washington State has reached $4.93 per gallon, topping California ($4.86/gallon), by 7 cents, according to AAA. Both states are still well above the national average of $3.58 per gallon. Brian Szasz, the stepson of billionaire Hamish Harding who is aboard the missing Titanic-bound submersible, spoke out & deleted his Twitter account after facing backlash for his tone-deaf posts Szasz's controversies began on Monday, as he shared a photo of himself at a Blink-182 concert. Zasz then attempted to clear the air after he flirted with OnlyFans model Brea on Twitter See omnystudio.com/listener for privacy information.

In a long-awaited action Wednesday, the EPA finalized its Renewable Fuel Standard (RFS) program establishing biofuel volume requirements for 2023 to 2025. However, the finalized program veered from the proposal the agency unveiled late last year which would have implemented a new credit system to incentivize EV manufacturing and purchasing. Over the past week, the average cost of regular unleaded in Washington State has reached $4.93 per gallon, topping California ($4.86/gallon), by 7 cents, according to AAA. Both states are still well above the national average of $3.58 per gallon. Brian Szasz, the stepson of billionaire Hamish Harding who is aboard the missing Titanic-bound submersible, spoke out & deleted his Twitter account after facing backlash for his tone-deaf posts Szasz's controversies began on Monday, as he shared a photo of himself at a Blink-182 concert. Zasz then attempted to clear the air after he flirted with OnlyFans model Brea on Twitter See omnystudio.com/listener for privacy information.

Golden State tarnished: Ex-pats reveal ‘why we left California for good' It's official: California dreamin' has become a nightmare. According to the California Policy Lab, which is affiliated with the University of California, the number of people leaving the state is up 12 percent since before COVID-19. In fact, there are more people heading out than coming in. Even before the pandemic, a survey from Edelman Intelligence found that more than half of residents in California said they wanted to high-tail it to another state. Among millennial residents, it was almost two-thirds. https://nypost.com/2022/01/22/former-residents-reveal-why-we-left-california-for-good/ California governor responds to recommended reparations payments... View Article

Silvergate Capital informó que planea cerrar sus operaciones y liquidar voluntariamente miles de millones de dólares en activos de Silvergate Bank. Gavin Newsom, el gobernador de California no reanudará contratos con Walgreens, Uber podría separar su división de logística carga. $SI $WBA $UBER $CS $SIVB $HLT

This week we're covering dissolutions, as a reminder that entities no longer have to dissolve by December 31.

Pide Gobierno de Baja California no eliminar el horario de verano México y Marruecos negocian que la aerolínea Royal Air Maroc opere en el AIFALa Secretaría de Hacienda mantiene el subsidio de 100 por ciento a las gasolinas y el diesel

En esta Semana Santa 2022, de las 290 playas revisadas por la Comisión Federal para la Protección contra Riesgos Sanitarios (Cofepris), sólo Playa Hermosa, en Ensenada, Baja California, no es apta para bañarse en ella, mientras que 99.6% de las playas son clasificadas como aptas, de acuerdo con los resultados del primer muestreo del programa Playas Limpias 2022.Los análisis de laboratorio realizados en más de mil novecientas muestras de agua de las playas de mayor afluencia pública de los principales destinos turísticos del país, casi todas tuvieron menos de 200 puntos de enterococos por cada 100 mililitros de agua.La mayoría de las playas estuvieron por debajo de 100 puntos de enterococos por cada 100 mililitros de agua, pero hubo algunas que estuvieron por encima, como son Playa Rosarito II (175), Zihuatanejo playa principal (166) y Playa Mocambo (112), en Baja california, Guerrero y Veracruz, respectivamente.

QUESTION PRESENTED:Whether states with interests should be permitted to intervene to defend a rule when the United States ceases to defend.Date                    Proceedings and Orders (key to color coding)Jun 18 2021 | Petition for a writ of certiorari filed. (Response due July 23, 2021)Jul 09 2021 | Motion to extend the time to file a response from July 23, 2021 to August 23, 2021, submitted to The Clerk.Jul 12 2021 | Motion to extend the time to file a response is granted and the time is extended to and including August 23, 2021, for all respondents.Aug 23 2021 | Brief of respondent United States in opposition filed.Aug 23 2021 | Brief of respondents State of California et al. in opposition filed.Aug 23 2021 | Brief of respondents City and County of San Francisco, et al. in opposition filed.Aug 23 2021 | Brief of respondents Washington et al. in opposition filed. (Distributed)Sep 08 2021 | DISTRIBUTED for Conference of 9/27/2021.Sep 08 2021 | Reply of petitioners Arizona, et al. filed. (Distributed)Oct 04 2021 | DISTRIBUTED for Conference of 10/8/2021.Oct 12 2021 | DISTRIBUTED for Conference of 10/15/2021.Oct 25 2021 | DISTRIBUTED for Conference of 10/29/2021.Oct 29 2021 | Petition GRANTED limited to Question 1 presented by the petition.Dec 13 2021 | Brief of petitioners Arizona, et al. filed.Dec 13 2021 | Joint appendix filed.Dec 14 2021 | Blanket Consent filed by Petitioner, Arizona, et al.Dec 17 2021 | ARGUMENT SET FOR Wednesday, February 23, 2022.Dec 17 2021 | Brief amicus curiae of America First Legal Foundation filed.Dec 20 2021 | Brief amicus curiae of Immigration Reform Law Institute filed.Dec 20 2021 | Brief amici curiae of Ohio, et al. filed.Dec 21 2021 | Record requested from the U.S.C.A. 9th Circuit.★ Support this podcast on Patreon ★

BAJA NUESTRO APP EL SHOW DE CHIQUIBABY PARA IPHONE: https://apple.co/32s0aYN PARA ANDROID: https://bit.ly/2ZAwR4q COMUNICATE DIRECTO CON NOSOTROS VIA WHATSAPP EN USA +1-323-690-3557 TELEFONO = 323-988-3868 info@chiquibaby.com

We're getting down to the end of the 2021 college football season, and Carla and Crappy are ready to discuss the New Year's Six bowl games – including the two semifinal games featuring Cincy vs. Bama and Georgia vs. the, uh, Big Ten representative – but first, we've gotta throw it back.   How far back? All the way back to last season, when COVID decimated college football schedules from coast to coast. The 2021 season was largely free of similar COVID hassles, until omicron showed up and started ripping through teams, college campuses and, inevitably, the bowl schedule. As of Thursday, Dec. 30 – the day the NY6 games are scheduled to begin – none of the big boy bowls have been overtaken by omicron. But we wouldn't be surprised if it happens.   Actual football. Let's go. The undercard: 7 p.m. Thursday, Dec. 30, ESPN Peach Bowl, Atlanta No. 12 Pitt vs. No. 10 Michigan State Two Kens are sitting this one out, but one Ken – a Kenny, specifically, is harder to replace than the other. And that's not good news for Pitt.   1 p.m. Saturday, Jan. 1, ESPN Fiesta Bowl, Glendale, Arizona No. 9 Oklahoma State vs. No. 5 Notre Dame It could be that the biggest variable in this game isn't a player – it's a coach. ND's players were clearly stoked about the selection of Marcus Freeman as the replacement for that dude who moved to Baton Rouge. And we suspect they're going to play their butts off for him.   5 p.m. Saturday, Jan. 1, ESPN Rose Bowl, Pasadena, California No. 11 Utah vs. No. 6 Ohio State Utah is playing in its first Rose Bowl, and it brings in a blueprint very similar to the one the Team Up North used to beat the Buckeyes. And that's got Crappy feeling really uncomfortable.   8:45 p.m. Saturday, Jan. 1, ESPN Sugar Bowl, New Orleans No. 7 Baylor vs. No. 8 Ole Miss Defense wins championships. Baylor is hoping that it also wins Sugar Bowls.   And the Final Four:   3:30 p.m. Friday, Dec, 31, ESPN Cotton Bowl, Jerryworld No. 1 Alabama vs. No. 4 Cincinnati This is the time of year when Nick Saban almost never loses. And that doesn't bode well for the Bearcats.   7:30 p.m. Friday, Dec. 31, ESPN Orange Bowl, Miami No. 3 Georgia vs. No. 2 football team Carla thinks the Bulldogs can win if they force the other team to rely on its passing “attack.” Crappy just seems to be really bitter about something … we're not sure what.   With a brief nod – it was more of a cringe, actually – to the Browns and Stillers on MNF, C and C wrap things up with just one show – the natty edition – still to come. Do your best of overdose on college football while you can, boys and girls, because it's almost done until next fall. Enjoy the games, yinz.

Que tranza tragones el día de hoy estamos de manteles largos con leon avena socio de los “pinches tacos” y también Jorge muñiz chef del flor de nogal, de los mejores restaurantes del país… por fin tuvimos un episodio donde hablemos de la comida y se puso bastante perro… espero con lo disfruten junto con una manzanita California No se olviden de siempre comer en la calle y lavarse las manos

Cinnaholic, a gourmet cinnamon roll bakery, was founded in 2010 by a husband and wife team in California No freezers, rolls are made fresh everyday Menu is 100% vegan and over 20 frostings and toppings Owners went on Shark Tank in 2014, deal fell through so they decided to go into franchising shortly after that. Each location has their own Facebook and Instagram page 59 units opened right now Menu Innovation  Have to think USA and Canada from a sourcing perspective Change flavors at least 5 times a year Don't focus on being 100% vegan in marketing Future of Cinnaholic — lots of growth and new markets!

A record-breaking number of cargo ships are anchored off the coast at the ports of Los Angeles and Long Beach. But posts on social media are falsely claiming that these ships are deliberately being prevented from unloading their cargo. What is the real reason? Is it a lack of personnel or a lack of brains? Leave a comment and let me know if you have any suggestions on how we can fix this problem.https://abc7.com/port-backlog-of-los-angeles-long-beach-container-ships/11142891/https://ktla.com/news/local-news/gridlock-at-l-a-county-ports-cause-major-shipping-delays-supply-chain-crisis/Support the show (https://www.buymeacoffee.com/johnmalone)

From the state that's untouchable like Eliot Ness, goals from Benji Kikanovic and Chofis each felt like slugs to the The post Tectonic Takes Episode 62: California No Love Lost appeared first on Beautiful Game Network.

TWR S1 E72: 36 Hours To California? No problemo!   Episode 72 of the Travels With Randy Podcast is here! Well, it's happened again:  Randy has made ANOTHER trip clear across the country since our last show a week ago. Randy is snug in his cabin in southern California this week and feeling a little sentimental as he preps the cabin for sale.  He has been in 14 states in the last 10 days and has loved every minute of the trip. Randy and Bubba talk about Randy's trip this week, and also talk about Elon Musks' Saturday Night Live appearance and his almost constant trolling the crypto markets with Dogecoin and Bitcoin talk.  Bubba, who lives in the southeast, relays his experiences with the crazy, sudden gas outage caused by the hacked oil pipeline.  Yes, he DID see someone fill up a Hefty bag with gas, because of course he did.  Listen on iTunes, Spotify, and everywhere else! You can also listen here: https://travelswithrandypodcast.libsyn.com/ #podcast #bitcoin #ethereum #masks #vaccine #ecommercebusiness #california #podcaster #ElonMusk #Route66 #podcasts #HousingMarket #travelswithrandy #PipelineShutdown #Charlotte #DOGEcoin #NomadLife #NewMexico #Texas #RemoteWorking

LA County COVID death toll rising In Los Angeles County, about two people are dying every hour on average from the virus, something the county's public health officer called an "explosive and very deadly surge." At Methodist Hospital in Arcadia on Thursday, frontline medical workers were among the latest to receive the COVID vaccination. "We've had this huge surge, because of the thanksgiving holiday and people getting together. There's no other explanation for the surge," said Dr. Bala Chandrasekhar, the hospital's chief medical officer. "And so please don't repeat the something at Christmas time. Because if you get sick there will be longer wait times and there may not be an ICE bed for you because of staffing or because of no ICU bed. We may not even have beds available for non-ICU patients. " According to the latest Los Angeles County data, 4,656 people were hospitalized with COVID-19 as of Wednesday. That number has increased by nearly 1,000 in less than a week. "If they need to be admitted we will keep them in the emergency room until a bed is available," Chandrasekhar said. "We are talking to all of our physicians to do early discharges for patients who can go home and get them out early in the morning so we can move them from the emergency room the the med surge rooms upstairs." Even if hospitals add more ICU beds, most don't have the extra staff to help with the surge of patients. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/essie-berry/message

Guests: Bob Zadek, Brad Dacus, and Brian Johnston 7/7/20 - Hour 1

Welcome back. These show notes will not be lengthy. This was recorded before Memorial Day and has no discussion of the last week's events, except for the intro. Here are three funds and groups we are donating the money from our Pro Flow Patreon tier to($300 total/$100 each) : Black Visions Collective MN: https://www.blackvisionsmn.org/ Reclaim The Block : https://secure.everyaction.com/zae4prEeKESHBy0MKXTIcQ2 Mass Liberation AZ: https://secure.everyaction.com/WmH46bWDq0y-gu9NoIQphQ2?fbclid=IwAR2lqApcG-vRHtI9Lo0FrZ_uBv6N1FCxTFyWlBs4GzEC8qeRRtI5_DopCQw Thank you to everyone who is actively working to dismantle white supremacy and to defund and demilitarize the police.

Episode 828 (July 10, 2019) - Mhoni vidente predice otro sismo para California - ¡No te puedes perder a Pancho Barraza en el estudio!  Learn more about your ad-choices at https://www.iheartpodcastnetwork.com

Not all California chardonnay is an oak bomb. Here are three excellent wines that prove the point. Click the link to purchase Cellar Notes recommendations at Kenilworth Wine ---- Spirits.

160 UFO sightings reported in Wash. state last year Article Link: https://komonews.com/news/local/160-ufo-sightings-reported-in-wash-state-last-year DAVENPORT, Wash. - Some 160 UFO sightings were reported in Washington state last year - about one every 55 hours on average, according to the National UFO Reporting Center. “Obvious hoaxes have been omitted, however most reports have been posted exactly as received in the author's own words," the center says. "We hope that this information will prove to be useful to the general public and the UFO community at large.” The center reports that Washington state has the third-highest number of total sightings in its database, behind California (No. 1) and Florida (No. 2). Some examples: Oct. 24 sighting by a former pilot in University Place: "Object was spherical in shape and emitted a brilliant, extremely coherent orange glow. ... The object made zero noise. As it approached my direction it just skimmed the bottom of the cloud layers, moving through cloud material and lighting it up with the same orange color it was emitting. It sped up and slowed down erratically and quickly, moving very much as a living creature would as apposed to human aircraft or drone would. ... It was quite strange." Show Stuff TeePublic Store - Get your UBR goodies today! http://tee.pub/lic/2GQuXxn79dg UBR Trurh Seekers Facebook Group: https://www.facebook.com/groups/216706068856746 Manny Moonraker: https://www.facebook.com/MannyMoonraker/ UFO Buster Radio: https://www.facebook.com/UFOBusterRadio YouTube Channel: https://www.youtube.com/channel/UCggl8-aPBDo7wXJQ43TiluA Google Plus Manny's Updated Google+ Profile: https://plus.google.com/u/0/+MannyMoonraker To contact Manny: manny@ufobusterradio.com, or on Twitter @ufobusterradio  Call the show anytime at (972) 290-1329 and leave us a message with your point of view, UFO sighting, and ghostly experiences or join the discussion on www.ufobusterradio.com For Skype Users: bosscrawler

160 UFO sightings reported in Wash. state last year Article Link: https://komonews.com/news/local/160-ufo-sightings-reported-in-wash-state-last-year DAVENPORT, Wash. - Some 160 UFO sightings were reported in Washington state last year - about one every 55 hours on average, according to the National UFO Reporting Center. “Obvious hoaxes have been omitted, however most reports have been posted exactly as received in the author's own words," the center says. "We hope that this information will prove to be useful to the general public and the UFO community at large.” The center reports that Washington state has the third-highest number of total sightings in its database, behind California (No. 1) and Florida (No. 2). Some examples: Oct. 24 sighting by a former pilot in University Place: "Object was spherical in shape and emitted a brilliant, extremely coherent orange glow. ... The object made zero noise. As it approached my direction it just skimmed the bottom of the cloud layers, moving through cloud material and lighting it up with the same orange color it was emitting. It sped up and slowed down erratically and quickly, moving very much as a living creature would as apposed to human aircraft or drone would. ... It was quite strange." Show Stuff TeePublic Store - Get your UBR goodies today! http://tee.pub/lic/2GQuXxn79dg UBR Trurh Seekers Facebook Group: https://www.facebook.com/groups/216706068856746 Manny Moonraker: https://www.facebook.com/MannyMoonraker/ UFO Buster Radio: https://www.facebook.com/UFOBusterRadio YouTube Channel: https://www.youtube.com/channel/UCggl8-aPBDo7wXJQ43TiluA Google Plus Manny's Updated Google+ Profile: https://plus.google.com/u/0/+MannyMoonraker To contact Manny: manny@ufobusterradio.com, or on Twitter @ufobusterradio  Call the show anytime at (972) 290-1329 and leave us a message with your point of view, UFO sighting, and ghostly experiences or join the discussion on www.ufobusterradio.com For Skype Users: bosscrawler

NBA Free Agency has begun and boy has it not disappointed! We discuss LeBron going to the Lakers, as well as who followed him there. Also, we discuss Boogie Cousins going to the Warriors for pennies on the dollar. And we can't forget to talk about Paul George deciding to return to OKC for "unfinished business". We also step back and see how these moves have effected the Western Conference as a whole - as well as other moves made by Houston, Denver and other teams. https://twitter.com/paceandspacepod https://facebook.com/paceandspacepodcast --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/pace-and-space-podcast/support

EP 114 - 3 O'Clock in California (no weddings this time) by Drunky your Walt Disney World main Stay, Rhiannon who knows more about Drinking at the Disney Resorts than just about anyone & your Skipper, Dickrichie who spends more time at Disneyland than anyone else in Disney Twitter.

In episode 80, we bring you more of this week’s injustice! We start with a California proposal to waive all school taxes for individuals who do not have kids in public school. We also discuss a Massachusetts proposal to give all women free birth control. Plus, an Ohio lawmaker has been caught having inappropriate behavior. This and more on #InJustice.

In episode 80, we bring you more of this week’s injustice! We start with a California proposal to waive all school taxes for individuals who do not have kids in public school. We also discuss a Massachusetts proposal to give all women free birth control. Plus, an Ohio lawmaker has been caught having inappropriate behavior. This and more on #InJustice.

Hello Renegade Nation - Today's show wraps up the the true facts surrounding the Las Vegas shootings of October 1st, who benefits. Then I talk about the recent California wildfires in Sonoma and Napa Valley regions - official narrative and mainstream media are calling it wildfires - but the evidence proves very much otherwise! The third event I talk about is what we are being warned about that is potentially coming down the pike - and it is very troubling, to say the least, if this information is accurate and it plays out. As Always, Thanks for Listening, Everly Isbe LINKS: https://steemit.com/las/@tomm/george-soros-and-shorted-mgm-stock-before-the-shooting http://www.globaltruth.net/why-did-mgm-resorts-ceo-dump-over-80-of-his-stock-3-weeks-before-massacre/ http://www.zerohedge.com/news/2017-10-08/insider-trading-and-financial-anomalies-surrounding-las-vegas-attack Info about melting point of materials found in homes – either house fires or wild fires https://www.youtube.com/watch?v=Q2q7nN0JYWE National Institute of Fire and Safety Training http://www.nifast.org/blog/07/do-you-know-what-will-not-burn-in-a-house-fire/ Video of devastation in Santa Rosa, California – Big question: Why are the trees still there? https://www.youtube.com/watch?v=q8SIMFcZ2vA Jim Stone @ http://82.221.129.208/.zw0.html Steven Greer – TRUMP WILL DISCLOSE, THIS IS THE FINAL ACT (NEW UPDATE 2017) https://www.youtube.com/watch?v=mrkNmzsMSy4

Host Lisa Kiefer interviews UC Berkeley freshmen Joe Gleason and John Siano about their startup company ActivityAssist, bringing the field trip into the 21st century by digitizing the permission slip, fees, and attendance process with a mobile app.TRANSCRIPTSpeaker 1:Method to the madness is next Speaker 2:stay in Speaker 3:nor the snoop two method to the madness of vibe weekly public affairs show on k a l ex Berkley celebrating bay area innovators [00:00:30] and your host Lisa Kiefer. And today I'll be talking to two UC Berkeley students, John Siano and Joe Gleason about a startup they're involved with called [inaudible]. Speaker 2:Oh, activity assist. Speaker 1:You two are probably the youngest innovators I've had on this show. Would [00:01:00] you just introduce yourselves and talk about what you're doing here at UC Berkeley? I'm Joe Gleason. I cofounded activity assist. I'm from South Philadelphia. I went to high school in North Philadelphia and I went to a school where teachers had to pay for their own paper for schools, whether that meant permission slips, whether that meant homework. All teachers have to go to staples, pay with their own credit card and buy their own paper. So when I was 15 years old, I got one of my friends from outside New York and we started a company that digitize the permission slips for field shifts, [00:01:30] proms, homecomings, and sporting events. How old were you at 15 you were in high school? Yeah, exactly. Yeah. And so I started with my own, with our own physics teachers. Uh, and my friend was in a town outside Newark, New Jersey called in south orange and I started at a high school called central high school in North Philly. Speaker 1:And you are? I'm John CNO. I'm, I'm from Cupertino, California. I'm also a freshman here at Berkeley. I actually met Joe here. Um, both freshmen. That's right. Yeah, that's incredible to me. Okay. That's how I met Joe [00:02:00] here. Um, you showed me activity assists and um, you know, I just recently got started with the team as the director of business development. So I'm, I'm pretty excited to, you know, join the team and help the uh, website grow. Let's back up a little bit. You started this in high school and you brought it here to UC Berkeley. Can you talk about that process just a little bit? That's right. So, uh, basically how that went is before I came to Berkeley, there was just me and my co founder and he's at the University of Illinois and I came over here to Berkeley all the way from the east coast. Speaker 1:[00:02:30] And it was, we, we've always worked remotely. So that's never been a problem. But I think it's been interesting in that Berkeley has such a culture of entrepreneurship and innovation and you can find people and just tell your story and people will listen to you offer great criticism, great questions, and you can move on. It's such a great place to innovate and such a great place to share your story that it's, it's perfect for me. It was perfect for activity assist and that's the reason we're happy to announce we just raised $20,000 from the dorm room fund. Okay. So we need to explain [00:03:00] what is this dorm room fund? So the dorm room fund is a, a venture backed firm that invests in college startups across the country. They're based in the bay area in, uh, New York, Boston, Philadelphia, and I think they're expanding. So they're growing from a backed by first round capital and they invest in college startups on their average investment is about 20 k and we're happy to announce that we're one of the more recent investments. Speaker 1:Okay. I did a little bit of reading about the dorm room fund and they started in, is it 2012 [00:03:30] yeah, that's right. And they started in Philadelphia. Had you known about them at all when you had this idea in high school? So in my high school, a lot of my friends went to Penn just because of the nature of being so close to Penn. And I actually knew a couple of people on the dorm room fund in Philadelphia from my high school who had gone on and studied at Penn. And so I had known of the Dorm Room Fund for Awhile, but I knew activities just wasn't at the stage where we could raise the money that the money would be necessary. You know what, for what we need now [00:04:00] to build a brand name. Plus you were in high school, they didn't fund high school. Exactly. They didn't, they didn't fund high schoolers, you know, and we're surprised they even funded freshmen that were one of the youngest people that are funded. Speaker 1:So that is very exciting. Okay. So you knew about this fund and this fund was started by a company called first round capital. First round capital I think was the first company to invest in Uber. So they have this tradition of investing in very innovative and new ideas. So, um, they have [00:04:30] this division, I guess you'd call it, that controls the dorm room fund. That's right. How many projects have they funded across the United States? Universities? As of today? It's hundreds, hundreds, hundreds. I know my contacts from the bay area, Davey Bloom, Greg Guy, I connected us in the first place. I think they invested in an average of 10 a year per location. And that may, that number may fluctuate from year to year, but I think on average it's about 10 Raby last major across the country per location. So the four locations, [00:05:00] I would say 20 to 40 startups they invest in annually overall, nationwide. Speaker 1:And so we're one of that group, which is really exciting and it is exciting. And so you know, all of the INS and outs of, so what did you need here at cal to continue? So one thing I knew I needed was as I'm studying, as we're all studying, I needed a team. You need great people to make a great company, uh, and you need great people to help sort of mellow the highs and lows of startups. And so I said, okay, I need to find these people. So I said, I need a marketing [00:05:30] guy, I need a business guy. Are you a business major? I am not a business major. How Nice your major know science and Engineering Major was, you can say, oh, what's that engineering. And I just loved material science. You know what material sciences, you can tell me it's the study of how everything is made. Speaker 1:You found John. That's right. And um, what does it mean when you say you're a business development guy? So I help in outreach to schools, you know, such as like contacting schools, marketing, uh, finding teacher conferences. We can speak. I basically just to get the m word out for activity assist. [00:06:00] And uh, that's something that I've had experience with in the past. You know, in high school I worked on my own startup called study trove. And so I, I've kind of had a, where was this high school where you get to start doing a startup? Oh, it's called, it was called Cupertino high school. Just about 40 minutes away from here. I have to just intersect here and say I'm amazed that number one startups are happening in high school. So and also, and they continue on. I mean that's very exciting. So, so when I met Joe here, I was really impressed with how, how well activity assist the website was made, you know, he had all his numbers down [00:06:30] in terms of like budget, finance, stuff like that. Speaker 1:The website, he thought of all like edge cases. Like we like to say we built a website with teachers for teachers. So the whole product came about because our teachers came to us and we were designing the website. We every step of the way we showed it to our own teachers. And so you were in this high school where you were living this application? Exactly. We were building it and living it. I like to say I live for you, the neat activity assessed and so did my partner, you know, at his high school out in New Jersey. So, okay, let's go, let's talk in detail about this product. [00:07:00] And before you go into detail about that, is it up and running here yet? So activity assist is fully operational. Is it operational here in California yet in California? No, we are not live in and the schools in California citing part. Speaker 1:And that's what you're getting going here. So let's talk about the details of activity assist now. Great. So how it works is a teacher can basically go on our website, activity assist.com create activities like field trips, prompts those events, invite their students in chaperones to attend through the site [00:07:30] and then they can send permission slips to those parents, bypassing the kid. And then as a parent you can say your kid's been invited to attend the problem. You could sign and pay for that prom right from your email. No login required. So it's a, it's a completely online process. It's taking the old permission slip and modernizing. We're bringing the future into the 21st century. Okay. So how would a student, you know how in the old days you could, you could game some of these things and put a signature down for your parents. It wasn't your parents things, your, how are you getting around [00:08:00] any kind of fraudulent activity? Speaker 1:So fraud is a good, is a good question. Uh, we sort of covered that with uh, on the student side if any student tries to intercept the parent email, you know, in sign and pay for themselves digitally. What we do at the beginning of any school onboarding, we send a form home, one form that says who we are, what we're doing, and we ask the parent to legally give them, give us the most accurate email address, the one they check most often and then they have to sign therefore covering our liability. So if a student does happen to [00:08:30] access the parent's email signing pay online, we're not liable. So, okay. Yeah. So you get an electronic signature. That's right. We use docusign. Yup. We take care of that online. And it's really nice because one thing we did is we, we launched a bunch of focus groups with parents and parents are the one thing they hate most, I don't know about you is the logins. Speaker 1:They absolutely hated login. So what we did is we did something pretty unique. We, we built a link that only works with that particular. So if I send you an email saying your son or daughter has been invited to attend the senior prom, [00:09:00] only you can access that link from your computer. No one else can access that link. If someone accidentally gets access to your inbox from another, like another place, they can't get it. That's really great security. That's where it's important. So, um, you've been at this since, what year was that? Must've been 2014. The summer of 2014. Okay. Did it become profitable out in Pennsylvania? So we've been actually working on this site for about a year and then we built a mobile app. And what the mobile app does is it lets chaperones, let's say on the day of the Prom, take attendance. So as a kid comes into, say John's coming [00:09:30] into the problem, I can tap them in on my phone and send an attendance report directly to my school. Speaker 1:So there's no paper attendance list. It automatically updates to the system. And so we spent a whole bunch of time building that and then I sort of had to do the business and I did a lot of fundraising. So uh, in the beginning I started out, I self funded most of the business and I raised a lot of money from go fund me, uh, approximate about like 8,000 total among in that first round is now let's talk about what is go fund me. Go Fund me is an amazing website. Go check it out. Go Fund me.com. How it works is you go, [00:10:00] you, you make your campaign say ah, there's a lot of medical cases, a lot of educational cases. I know one, I know one friend who wanted to go to Pittsburgh and so he'd put on his, he launched the go fund me campaign advertising, how he loved robotics and how he wanted to go to Pittsburgh. Speaker 1:So this is a crowd funding sec donation crowdfunding and he raised the money that he could use to live and go to school in Pittsburgh. So it's really amazing. And it sounds like it's geared toward educational and it's geared towards educational things. It's geared towards things that the people you know want to pay for to [00:10:30] in a, in a high school startup. So you started this and then you got the attention. How did you get this $20,000 raise from dorm room fund? So I spent probably the last two months of going to events, pitches, competitions, talking to everyone. I could try to fundraise this one where we have a goal right now, 50 k over the next 12 months. That's our fundraising goal. And we've raised 20 from the doormen fund. So how do we do it? I was going from competition and competition. I'd probably, I'd probably pitched to 35 vcs with 30 vcs trying to raise this money. Speaker 1:[00:11:00] And you know, vcs were a small fish in a big pond. They don't want to invest in us. And so then we, we eventually found, I remembered, oh, the dorm room fund and then I tried to reach out. I knew a guy, I know a dorm room fund just to back up. It's run by students. That's right. It's run by Grad and undergraduate students at Berkeley and at Stanford, at least in the bay area. And so I knew a guy named [inaudible], his name's Brian Dunn. He manages the, this awesome consulting group at Berkeley called the two mead consulting group. It's an, it's an Israeli consulting group and he knew David Bloom who was sort of my [00:11:30] account rep at dorm room fund and he connected us last semester we chatted and got to know each other and then we reconnected this semester when I was fundraising and it just, it seemed like it worked and then we did a pitch, we made it and we're in, so you have 20,000 when did you get this money? Speaker 1:How long ago? We got the sort of like the acceptance about two weeks ago and then we're getting the money. Right. So you're up and running now and you're reaching out. How are you using that money right now? So we have an itemized budget. A couple of things for launching an online advertising campaign, launching a direct mail campaign. [00:12:00] Direct mail is like sending pamphlets to, to schools, you know, seeing something that you can hold in your hand. Oh we're looking at, as John mentioned, Ed Tech Conferences and teacher conferences. We think this is a word of mouth game, sort of getting this in teacher's hands because of that. At the end of the day, the teacher is our best consumer. They're the ones who are benefiting from this. They're the ones who love it. And I've not met a teacher who hasn't loved this product. It's so simple. So we need to get into those conferences. Speaker 1:And then also I'm looking to hire a couple people. So that's our fundraising outside of school mentor [00:12:30] or Advice, I mean cause you know, you come into this bay area, there's a lot of teachers and what help are you getting? So what help am I getting? I think it all started back home. Uh, when I was in middle school. Eighth Grade, eighth grade, my mom started a company I called Jelly Arts LLC. It's an art product. It's for printmaking. And so when we were first starting out in eighth grade, she was, she was shipping out product four to five pieces a day. And I would come home everyday school ended at three 30. I would run home packing ship boxes, run to the post office [00:13:00] by four 30 cause I had to get the rent four 30 otherwise I couldn't sit about product for that thing. And I have that product for my mom's saw business from my basement every day for a year, you know, and I got to see her business grow and now it's a million dollar company. Speaker 1:You know, it's, it's exciting, you know, after a lot of years. And I got to grow with that business, I got to see the mistakes she's made and she's totally been my advisor on this. Uh, my dad started a company too when he was younger. They've been my advisors. And so you grew up in a household like I did. We're a household of entrepreneurs. That's the only way around it, John. Yeah. So, um, you know, my household [00:13:30] also has been, you know, very proactive and know creating things. And um, so for example, when I was in high school, I mentioned I created my own educational startup called study trove. My parents were very active study trove. It's basically an essay edited being a website for schools and still operational. But through running that, I realized some of the mistakes that I made. And when talking to Joe, when he introduced me to activity assist, I realized a lot of those mistakes that I had made in the past, those were corrected in an activity assistant. Speaker 1:That's what really attracted me to joining the activity assist team. I [00:14:00] was just really impressed with the product. Well, there's nothing like failure to help you understand what you need to do. You can always learn from your mistakes. And I like to say, what does it like to run a small company? Uh, this is what it's like. One day you get the dorm room fund and you leave the meeting and you're saying, oh my God, we're going to make it. We're going to be a $10 billion firm. We're going to have an IPO, it's going to be amazing. The next day you're gonna have a call with the customer. It's not going to go so well. You're going to leave that meeting and you're going to say we're going to dissolve and three months it's not going to work. All this stuff. So working [00:14:30] a startup is kind of like running a wave. You've got to sort of balance the, the ups and the downs and mellow it out. So on your good days you have to say, look, we're not, we're not there yet. And on your bad days you get, you got to say, oh well we got this going for us. And I like to say my blood pressure is going through the roof all the time. Speaker 3:If you're just tuning in, you're listening to the method to the madness. [00:15:00] A biweekly public affairs show on k a l x Berkeley Celebrating Bay area innovators. I'm your host, Lisa Keifer, and today I'm interviewing two innovative UC Berkeley students, John Siano and Joe Gleason. They have a startup called activity assist that empowers teachers to create digital permission slips and send them off to parents instantly who can then grant permission and pay electronically while [00:15:30] letting chaperones take attendance on the day of the trip through their mobile app. Speaker 1:Tell me what your immediate goals are and then later goals. Cause you know, you just, you're just getting started here in the bay. That's right. That's right. So our immediate goals are traction and that's just getting the word out schools and getting our name out and that's getting us in teachers hands. I'm willing to give this product away to, to schools for free in the intermediate time, uh, for this year, for [00:16:00] the remainder of this year so that we can get them for next year. You know, a lot of public schools finalize their budgets by July 1st so we're really pushing for that July 1st deadline. What do they have to pay to get started? Right. So we charge $500 per school per year. A but when you're first starting out, we're going to give it to you for 30 days. Try it with a couple of trips and make sure you like it and make sure it works with your data and then go for it. Speaker 1:Uh, it's $500 per year per school. We don't charge per pupil. Well, you know, budgeting is really tough here in California public schools. [00:16:30] Are you also approaching private schools? We are. We are looking at private cause I was, you know, I mean they may not have that mudget budget after the field trip expenses to pay $500 sounds crazy, but it's a lot. So when I was first starting out, I did a lot of research, I did a lot of research and one thing that I found was that even these public school districts that are strapped for budget space, one place they are not strapped for, or they at least have a little bit more about room is their ed tech. They usually have 10 to 30 k available to [00:17:00] invest in things like this every year. So there's totally budget space and a lot of schools now for talking city schools that Ed tech budget space is not there. Speaker 1:But if we're talking suburban middle class, you know, family schools. What about Oakland Public Schools? Oakland public school, inner cities, inner city school districts, different story. I'm from Philadelphia, which is, I think it's the second worst public education system in the country behind Detroit. And I actually worked at a company in high school where we worked with teachers and principals to w [00:17:30] w we raised money for them or we gave money, we gave them grants. And one thing I got to do is I got to meet principals. I remember one story I heard was someone was, had a meeting with the principal. They were walking down this hallway in their high school in South Philly high and they would walk in a classroom and they would see the teacher at the desk with their feet on the desk with the magazine in their hands. The kids running aimlessly. Speaker 1:They'd walk in another classroom pitch black textbooks piled from the floor to the ceiling, some three years old, never used. And so there's totally a misallocation of resources in city school districts. [00:18:00] And we recognize that. I definitely do coming from Philadelphia, and I want to sort of tackle that. I don't want teachers to have to pay for their own paper. It's ridiculous. If you're going to go on a field trip, it requires buses. There's a lot of other expenses besides the paper. So, so the buses bus drivers are actually paid. They have tenure. Usually they usually, they have an hourly schedule, so they're already running around with a sporting events in cities. I know, I know Philadelphia at least. Uh, there's bus drivers going around all the time because of the inner study supporting us spreading clubs. [00:18:30] Yeah. But do you get my drift here? Speaker 1:I mean, when you're talking about inner city school, so number one, you have to assume, do they have buses? Do they have the budget? Do they have, can they send out a bunch of kids to, there's one thing we charge $500 per school per year for schools that can afford it. So for inner city schools, we're going to actually give activity system for free because we know that those school districts on average have 300, 400 schools. They can't afford a product like this, let alone something even cheaper so we can stand only stand to benefit [00:19:00] by giving it to them. So we're going to give it to them. It's a mutual benefit. They can save money on paper. Their teachers can save a bunch of time. What if you start to make money? I mean just theoretically this thing takes off like crazy. Who gets the money? Speaker 1:Does do University of California Berkeley get any money or is it strictly go back into your pocket or does Dorm Room Fund get money? Activity assist is an LLC of New Jersey and so we're, we're a for profit private company us the money will go to the owners, just a funding round. They Invest 20 K in permits [00:19:30] or a note, which is a sort of a debt vehicle. So technically we owe them the money back. So you've paid us back and everything else is yours. So the Dome Room Fund is full of students as well? Yes it is. So if they're taking equity that students who are becoming vcs and making money on other student projects. So true. So I work, I work part time for a company called personal capital in San Francisco. And Mike, why are you studying? That's a different guy than say a better question is when do I sleep? Speaker 1:And so on. My boss there were at the Dorm Room Fund at Berkeley, [00:20:00] he's a Hoss Grad and uh, and he always likes to say working with the dorm room fund is like working with for VC firm and you're managing the VC and firm as a kit, you know, which is like crazy, you know, cause your budget is kind of limitless and you can invest in all these cool companies, but you have to, you have to be careful, you have to be cautious and it's, you learn what it takes to invest and work in the investing world. So working for the government fund is a great opportunity. Anyone out there and then you get picked for that. Oh well it's kind of like you've got to network your way and you know, you gotta you gotta talk. So if you know someone, [00:20:30] you go talk to them, see what you can do. Speaker 1:I definitely recommend it to anyone out there who's saying, oh, the Doberman fund sounds awesome. I should go do it. It's totally worth, yeah. Especially like business majors in this major house. Oh, MBAs. Yeah, yeah, yeah. Well even you guys, after you're done with this project, you could be on the Dome Dorm Room. Who knows? John, what do you think? I think it's a good idea possibly, but I'd rather focus on this for now. Okay. Let's get, John, let's talk to you a little bit. Um, what is your major here at cal? Um, I'm a business major and a computer science major. Are you bringing computer skills to activity [00:21:00] assist? I'm currently, I'm learning more and more so I'm hoping that, you know, like for example this summer I'm going to be scaling up a bit. So I hope to, you know, continually bring stuff to the company. Speaker 1:Are you using big data on this or is it too early? Too early. Too early. But we have plans we have planned. Okay. So let's assume you s you start doing well and, and people get wind of your company. I know that some of the dorm room fund projects have gone on to y Combinator and other places like that and you know, taken off like a real company. Are you ready for something like that? What, [00:21:30] I mean, could this happen I think possibly a year from now that could be the best place for us to go? Quite honestly, you y Combinator is an excellent program. I like that they pick you or would you approach them? How does that work? You apply and they pick you, you interview, you go for it. That's how that works. It's a huge, it's a very small acceptance rate, uh, probably on the, on the level of Stanford's [inaudible] and uh, so yeah, you apply and I think next year wouldn't be great for us. Speaker 1:We're not where we are. We're not where we need to be. Do you have numbers that show that what you're actually [00:22:00] saving schools yet? Yes. So, so why we even started this was because a physics teacher came to us and was managing his own trip. He spent two weeks trying to manage a physics trip and he tried to manage over $10,000 for one field trip and he had to waste two weeks of class time, prep time trying to deal with this. And so in terms of teacher time, we saved schools with the most money in terms of teacher time. So what that means is if the average teacher's salary is 60 k which it is in New Jersey, we can save you somewhere in the neighborhood of five to 6,000 in terms of teacher trial [00:22:30] opportunity costs, no, that's money. Not like liquid money, but that's money that teachers could otherwise spend in the classroom. Speaker 1:You know? So there's a benefit there that you don't have to waste time passing on a trip for to every kid in my class and saying, Johnny, where's your trip form waiting two weeks for this, you know, trying to track it down. Instead you could set version subs out in the morning. Every parent can see it while they're at work in their email, send it back and you can be done in a day or two rather than weeks. Also in terms of managing it, it's really simple. All the payments run through the site so you can track all of that and it's all covered. [00:23:00] It's really something that's good. And what do you think the greatest challenges are here? You're a California and so what do you think your greatest challenges are going to be? Probably the greatest challenge that I see is just getting the word out to schools because everyone who's seen the product, they've loved it. Speaker 1:You know, not only teachers but also conferences we've been at. They've also, this is a fantastic idea and we just need to get the word out so people know that this is a service that's offered. And I feel that once people, once we have like market saturation, everyone will want to jump on this product. It seems like in the public [00:23:30] school system you would go to, you know, the county offices or you know, the head person. Have you thought about going to Sacramento and the Department of Education and presenting to those people? So Sacramento and cities of that magnitude, we're not, we don't want to go into deep yet. You know the big cities because we want to sell, we want to sort of start out smaller and make sure that everything's working, you know, doing the kinks. Our targets are small public school districts right now and private schools on the individual basis. Speaker 1:We want to start out with, you know, 20 schools fine [00:24:00] to the kinks and then see, okay, how can we get into central that you have that list right already, right? We have targets of your targets and you're beginning to, yes we are. You know, you obviously have this background in entrepreneurship and everything. When did it all become a reality for you? I like to say that it started out with Evan and I and our basements, Skype calls every day after school. We would mock up the website, we would design it. In the beginning we were designing this product as a tool for our teachers. It was not a business and so when did it become a business [00:24:30] and it's kind of like, I think it's kind of a gradual thing. I think that's when you start to talk about, oh, when you start to run focus groups with teachers and you say, Oh, and you're talking to them. Speaker 1:I think the moment for me was when we sat down in a room of 30 30 teachers, showed it all to them anonymously. Each one of them said they loved it and that they needed it for their own, for themselves. You know, it was so simple. They could do it in five minutes and be done. Been pretty exciting. Oh, I was so excited to meet you. This was a high school basement runs Skype project. I like to say that [00:25:00] those teachers, every single one of them said they loved it and that to me was a moment we can tell entrepreneurs are, can be made or are, are you born an entrepreneur? I think it's totally a, a like a malting process. You have to go through the cauldron of becoming an entrepreneur because it's not as, yeah, you know, it's not as a, it's not as simple as like going and just like coming up with an idea. Speaker 1:There are a million ideas out there. A true entrepreneur doesn't need a hundred ideas and entrepreneur can [00:25:30] have zero ideas, but if they find someone with an idea, a true entrepreneur executes, they devote themselves, they grind, they talk to people, they know their consumer, and then they move forward. And that's what an entrepreneur does. They're an executioner. They're not an ideate an idea, you know they're an executioner. Okay. John, do you agree with that? I mean, what do you feel like, what is the definition to you of what you grew up in an entrepreneurial family? Do you think that you, it's natural or is it learned or can it be acquired? I've been, I'm going to go with [00:26:00] kind of a boring answer. I think it's kind of half and half. Just referring back to what Joe said, it's kind of like a call driven that there's going to be a lot of moments in which you feel, oh, this isn't working, or maybe my idea isn't as great as I thought it was. Speaker 1:But if you keep pushing forward, you know, you keep developing your product, your keep learning from what the customers want and you just keep going. Then I think that's what can help you succeed in entrepreneurship. And just as Joe said, it's not just about the idea because anyone can can come up with a fantastic idea. You've got to go out there and execute and actually get it done, get sales, that type of stuff. [00:26:30] And besides execution, it's also a determination. Being an entrepreneur is taking those 4:00 AM nights. You know, if you have to meet a deadline, then you have to meet a deadline and no one's gonna come and cover you. You have to take care of it yourself, you know, so it's knowing that you, that you're fully responsible for it and you take ownership of it, but you love it. All the same. Speaker 1:You love every moment. You'd have to love it. You have. So if you guys get incredibly rich, are you going to drop out of school? Don, you answered that first. Will you need school anymore? I think school would be a nice, a nice backup to [00:27:00] have. Um, right now we're doing a pretty good job of balancing it though. So, um, I guess we'll just wait and see to where this takes off. Um, but for now we're, we're doing pretty well in both school and activity assist. Yeah. So how would any interested listeners get ahold of you? So to anyone out there who's interested in working on the business side or on the back end or as a full stack developer, definitely go to our website, www.activityassist.com. Reach out to us on our contact us page. Check out how the product works. [00:27:30] If you're a parent, go to our website, see how we can save your school time. Speaker 1:Talk to your teachers, talk to your friends, do see what you can do. See if you liked the product, go check out our video, I n to anyone out there who's just a young entrepreneur, definitely go and see what you can do. I would say if you have an idea and you have a, if you have a team, if you have some friends that you know, let's tackle this, do it. Don't hesitate. Take, take control. It's the greatest experience you'll ever have. And you and we should. They go look at dorm room fund. If they have traction, if they have a business model, if they have the team, [00:28:00] then later you can fundraise. I think in the beginning it's about how do we talk to our consumer, how do we make sure the market needs this product? And then it's how do we build a great team? Because like I said, you need great people for a great business. Yeah, I would say you don't just go out there and be proactive. I think it's better to fail and learn from that experience than just sit back, be complacent and not do anything and also go out there and be proactive. That's it. Well, Joe and John, thank you for being on this program today. You are absolutely the youngest entrepreneurs that had been on my program. I mean, I'm impressed. [00:28:30] So activity assist. Congratulations. Yeah, Speaker 3:and good luck on your project. Very nice. And that was UC Berkeley students, John Siano and Joe Gleason. They're only freshmen, but they've started a company called activity assist and recently received $20,000 in funding from the dorm room fund. Their idea is to empower teachers to create digital permission slips and then [00:29:00] sending them off to parents instantly who can then grant permission and pay electronically while letting chaperones take attendance on the day of the trip through their mobile app. You've been listening to a method to the madness, a biweekly public affairs show onK , a l ex Berkeley celebrating bay area. Innovators. Tune in again in two weeks at the same time. See acast.com/privacy for privacy and opt-out information.

We've all heard that too many cooks can spoil the broth, but that's hardly the case on today's episode. The new FRESHMeals collection of recipes for schools is the work of several dozen cooks from 18 "California Ambassador" districts, pledged to mentor and share best practices state-wide. It took more than two years of tightly coordinated trial-and-error to build a database of 140 (so far) dishes that are off-the-shelf school ready—fully vetted for practicability, affordability, customer appeal, and compliance with USDA meal standards. Not in California? No problem. FRESHMeals are available online, to everyone.

Host Lisa Kiefer interviews Innovative Genomics Initiative lab member and UC Berkeley post-doc Mark DeWitt, PhD., about the perils and promise of the CRISPR-Cas9 gene editing technology.TRANSCRIPTSpeaker 1:You're listening to method to the madness at my weekly public affairs show, k a l x Berkeley Celebrating Bay area innovators. I'm your host, Lisa Kiefer, and today I'm going to be interviewing biophysicist Mark Dewitt. We'll be talking about gene editing, both Fitz promise and itch perils [00:00:30] as well as his work here at the innovative genomics initiative lab at the La coshing center for Genomic Engineering on the UC Berkeley campus. Welcome to the program, Mark. Thanks for having me. Speaker 2:You're a biophysicist a postdoc researcher at the innovative genomics initiative here on the UC Berkeley campus at the La cashing center for Genomic Engineering, and you're doing some exciting work on many [00:01:00] things and we're going to get into what you're doing. But before we do that, I want to talk about the golden age of gene editing and talk about some of the fundamental parts of that so that our listeners who are not scientists or biophysicists can understand what we're talking about. Here's UC Berkeley's very own professor Jennifer Doudna a few years ago with my colleague Emmanuel sharp on ta. I invented a new technology for editing genomes. It's called CRISPR cas nine the CRISPR technology [00:01:30] allows scientists to make changes to the DNA in cells that could allow us to cure genetic disease. The CRISPR technology came about through a basic research project that was aimed at discovering how bacteria fight viral infections. Speaker 2:Bacteria have to deal with viruses in their environment and we can think about a viral infection like a ticking time bomb. A bacterium has only a few minutes to diffuse the bomb before it gets destroyed. So many bacteria have in their cells [00:02:00] and adaptive immune system called CRISPR that allows them to detect viral DNA and destroy it. Part of the CRISPR system is a protein called cas nine that's able to seek out and cut and eventually degrade a viral DNA in a specific way, and it was through our research to understand the activity of this protein cas nine that we realize that we could harness its function as a genetic engineering technology, a way for scientists [00:02:30] to delete or insert specific bits of DNA into cells with incredible precision. The CRISPR technology has already been used to change the DNA in the cells of mice and monkeys. Other organisms as well. Chinese scientists showed recently that they could even use the CRISPR technology to change genes in human embryos and scientists in Philadelphia showed they could use CRISPR to remove the DNA of an integrated HIV virus Speaker 3:from [00:03:00] infected human cells. Okay. Mark, let's get a little bit more into this gene editing. Speaker 4:You can imagine that our genome is essentially like a document that has 3 billion letters. Those were the different bases in the DNA that makes up our genome, right? A 20,000 genes, 3 billion characters, which I think is about a million pages. This is an, if it was an award document, I think that would be about three gigabytes of data. Right? So is this one really long document and gene editing is quite simply the ability to edit that [00:03:30] document. Speaker 3:It's like a cut and paste system, right? And a global global positioning system. Speaker 4:Yeah. What Dean editing lets you do is you can now go into this document and before all we could do is really read it. We could just know what was in it. But now with, with gene editing, we have the whole edit menu, right? So we can go to a location within the genome, we can cut out a sequence that we want to remove and then we can paste in a new sequence. So for example, if you have a, uh, a gene, uh, with a disease causing mutation in it, you [00:04:00] can cut that disease causing mutation out and then paste in a healthy gene. Speaker 3:Right. Okay. So it's, it's Kinda two parts, right? You know, you've got the, the CRISPR. Okay. And that stands for clustered regularly interspaced short palindromic repeats. Yeah, Speaker 4:it's a pretty, it's quite a mouthful. Basically what happens is that the bacteria would store this array of short sequences. That's the CRISPR array. And the sequences would match the sequences of the invading virus viral DNA, Speaker 3:so [00:04:30] that if it ever came again, it would recognize it. Speaker 4:Yeah. If the virus ever came back, it'd be like, oh, I know you. And then it would end the way that it recognizes the invading that DNA from its own DNA is because of, it's in this CRISPR array, it gets put onto the cas nine nucleus and the nucleus goes to the finding invading DNA and chops it up, but it won't chop up your own DNA because you don't have any of that sequence. You provide a guide, you have the cast nine nucleus and then you provide a guide, which is like a little RNA guide. It's an RNA guide. Yeah, we do it. We do it with RNA. Other [00:05:00] people can use RNA that's transcribed inside the cell. We actually provide the RNA outside the cell and put it right on the cas nine so RNA as a sequence, just like DNA. The sequence of the RNA can match a piece of DNA somewhere in the genome. So when you provide the guide and the CAS nine at the same time they get together and they go find the part of the genome that matches the sequence of the guide. So the guy guide has literally a guide Speaker 3:so you can program the guide to tell it where to go. Speaker 4:Exactly. So it's very, very easy to, to construct different SDR [00:05:30] and Aes, different guide rns to direct casts down to different places and in fact that's a major advantage of CRISPR cas nine technology over other gene editing technologies where they're not so easily repurposed to go after different targets. We've been doing gene editing for I think about 10 years in the old days, you know? Yeah. You'd have to do a lot approach in engineering. You have to synthesize a lot of different constructs, you know, different plasmids to continue to make different reagents, send them into cells and then pick the best one. It takes a lot of work, maybe a whole team of people, right? If you're working at a company that have like a whole team of people that do just [00:06:00] protein engineering, whereas mcast nine if I want to make a cas nine reagent that targets anywhere in the genome, I essentially order, I can order a template to make the RNA by typing it into the computer. A company sends it to me a day later. I can make you know, 10 different targets, hundreds of targets, right? People have done thousands or hundreds of thousands at once and then take that, make the RNA in my lab, mixed that with the protein in the night and introduce it into cells and generally almost all the cells get at it or they at least get the cut. The turnaround is, I mean I have my undergrads [00:06:30] doing it. I have visiting students doing it. I do it all the time. Speaker 3:What kind of oversight can anybody like? I can recreate the polio virus. Speaker 4:I can't just order a huge chunk of DNA that is big enough to encode an entire virus, Speaker 3:but are there other regulations on who can order what? Speaker 4:There are for sequences that contain toxins or infectious particles Speaker 3:like the polio or something like that, the whole polio virus. Speaker 4:And you're not allowed to order those synthetically. Or if you are, you have, you have to demonstrate that you have the qualifications [00:07:00] to work with that kind of genetic material. But you know, in our case we're going after genomes that are already there. So it's like your genome doesn't have any, you know, infectious particles in it. It has nothing contained in what we order that actually causes a disease. Okay. We're just going after disease genes that are already there. Okay. So in some senses it's actually much safer because there's no information that we're providing to the cells that could cause a disease unless we, you know, really want it to. Whereas for example, uh, the older version of gene therapy was to do viral delivery of [00:07:30] genes. And so since you're working with viruses, there's always risk of side effects. Even though the viruses are essentially de weaponized, there's still issues of where it puts the DNA, whether it could evolve into a different type of virus, these kinds of things. Speaker 3:Okay. You know who Hank Greely is at? Stanford law school. Oh, that sounds fun. Okay. He Dura, he's the director of the center for law and bio-sciences down there and he calls a the CRISPR cas nine the model t of bio-science. Hmm. Speaker 4:I guess what he's thinking is the model t was not the first car [00:08:00] or even the first car to be manufactured and just as that CRISPR cas nine is not the first gene editing technology. We've had it for some time, but it is the, it is the most robust and it's the easiest to work with. It's the one that everybody is out getting and trying and using. I mean not people that, not just people that specialize in gene in genomics or genetics, but really everybody. Yeah, and that sense it is the model t. It's the first one. It's the first version of this technology that everyone can use. What is the goal of it? Right off the bat, it is completely changed [00:08:30] the way that we do basic research. So, as I mentioned, it's very easy to work with now even if you're not a specialist in gene editing, but you have a, you know, a favorite gene that you like to, you want to characterize, you can target and manipulate that gene in human cells with such ease that you don't have to be a specialist and you can target many, many, many, many, many targets at once. Speaker 3:And so you in, in other words, like a goal of eradicating a certain that's heritable Speaker 4:[inaudible] well, so first is this used in basic research and then the other [00:09:00] potential application for CRISPR cas nine gene editing, early gene editing in general. And this is indeed already sort of underway, is m for gene therapy. As I mentioned, you know, you could have a genetic disease and then in some part of your body and then we can synthesize and inject reagents that will correct that mutation, fix the broken gene. And instead of, in the past we've been able to introduce genes into tissues, but only we can't fix a broken gene. Now we can actually go to the broken gene and replace it with healthy [00:09:30] sequence. Speaker 3:Okay, mark, let's break away for a minute and tell our audience they're listening to method to the madness here on k a l x Berkeley. Mark Dewitt is a postdoc over at the innovative genomics initiative at La caching center for Genomic engineering here at UC Berkeley. It sounds like you can do it one of two ways. You can go in and and fix an individual's broken chain system, or you can go in and correct it in embryonically and then it affects generations [00:10:00] later down the road Speaker 4:potentially. That's called germline editing and that's where you're editing the human germline. So that means that you create a heritable mutation in an embryo or probably a a fertilized embryo. Once you create that mutation or once you make that change, you know that that embryo will be implanted into a mother. She'll, uh, the baby will grow up, they'll have that change and then that, that kid will pass on that, that change to their kids. Most therapeutic applications of gene editing aren't really focused on that. Instead, [00:10:30] we're really focused on, and at the IGI we're only focused on, you know, editing healthy adults or sorry, adult patients. So it's just about the individual. And so in that case, when we make the edit, it's not transmitted to their progeny. So if you have a disease of your, so for example, I studied sickle cell disease, if I correct the sickle cell mutation inside your bone marrow, your bone marrow will be corrected and it'll be fixed, but your germline, your eggs or your sperm will not. Speaker 3:And we don't want it to be right because didn't it arise out of a resistance [00:11:00] to malaria thousands of years ago? To me, that's the issue of going after a germline. You don't know. That Speaker 4:raises the possibility that there could be unintended consequences of introducing things of introducing genetic alterations into the human germline. And that's absolutely true. And that's one reason why I think that, especially at this stage, it is just way too premature to undergo that kind of undertake that kind of research. The other issue is that it cuts at the place. You tell it to almost all the time, but sometimes it cuts other places. [00:11:30] That's called off target cutting. So it's not on your target, it's somewhere else. It's off your target. What's the success rate? Usually though the frequency of off target cutting is, it depends on the application. It's usually on the order of 1% or less. So it's too bad. Yeah. But if you have 4 trillion cells, a substantial number of cells in a gene edited individual. So if one of those off target cuts causes a nasty side effect, like for example, it knocks out a gene that's supposed to protect [00:12:00] yourselves from cancer, but then you could, all it takes is one cell to be edited to be edited in that manner. This unintended manner to cause the cancer. Speaker 3:Weren't you in a paper recently? I think nature biotechnology where you guys came up with a bubble technique that avoids cutting. Speaker 4:Yes. So one way to avoid off target cutting is to just don't cut it all. What we found in that paper was is that if you use a a cast nine that doesn't cut it simply can't cut it all. It still creates a structure, DNA protein structure that is accessible to the [00:12:30] replacement sequence you're trying to provide. It's not nearly efficient enough to really drive the kinds of levels of editing that would be relevant. You can think of it as DNA has two strands, the famous double helix. What we found is as the task then goes and pries open those two strands and clamps really hard on one of the strands, but then the other strand is essentially released and is free and so if you provide a sequence of DNA that binds to that strand, it will get incorporated. Now you've opened it up, you can stick stuff onto it. The advantage [00:13:00] of that technique is that you get no, is that since there's no cutting, the chances of off target activity are vastly reduced. Speaker 3:Are you primarily working on sickle cell? Speaker 4:So sickle cell disease is a disease of your red blood cells and you know, we've known about the genetics and the molecular basis of the disease. For almost 70 years. I mean it's one of the oldest, it's the oldest genetic disease that we know about and it was the first genetic disease to truly be characterized. I mean right around the time we discovered the structure of DNA, [00:13:30] we were already figuring out how sickle cell, Speaker 3:right and it's a defect in only one gene, which is very different from a lot of other diseases. Speaker 4:Exactly. So we call that monogenetic versus poly genetic. It's a moto genetic disease and that it has exactly one cause and in fact that's all the way down to the molecular level. There is a single letter or a single base pair change in your genome that causes the disease. And so that change is in this gene called Hemoglobin Beta, which is one of the two proteins that make up hemoglobin, which is what makes your red blood cells red. [00:14:00] It's what carries oxygen, you know, from your lungs to the rest of your tissues. It's all going through this hemoglobin protein, hemoglobin protein that has this sickle cell mutation will aggregate inside the south, will form these long, these big clumps inside your red blood cells. And these clumps cause the cells to become deformed and adopt that, that this characteristic sickle cell. Yeah. It's more like a crescent moon. Speaker 4:I mean we're not farmers anymore. So I figured, yeah, we should update the language, but I sip like a crescent moon or a sickle. The sickle RBCs [00:14:30] well, first off, they're not as effective at carrying oxygen. So you have anemia, but also they can clog blood vessels and like your capillaries, they won't fit in your capillaries very well and that can damage the capillaries and also can lead to these crises where your blood vessels get clogged. So it causes that increased risk of stroke and pulmonary hypertension and also the damage to your blood vessels can cause organ failure. So it's a progressive disease in the sense that individuals in, in countries with developed health systems like the United States, their symptoms aren't very [00:15:00] severe and they're very manageable for the first few years of life. But then as they get older and older and older, um, increasingly severe symptoms will manifest. Speaker 4:And ultimately it leads to something like a 25 to 30 year detriment in lifespan. And it's an inherited disease, inherited disease, and we have two copies of every gene, right? Individuals that have one copy of this, of this mutation. So they have a mutated gene and the healthy gene are called carriers and they also have this clinical presentation is called from sickle cell trait and individuals with sickle cell trait [00:15:30] are generally healthy and also have some resistance to malaria. And that's how the, that's how this mutation is maintained in the populations in, in populations and malarial regions to Subsaharan Africa and southern India where the mutation first arose. The United States is not a malarial country, but of course we have a large minority of African Americans whose genetic heritage is from Subsaharan Africa from these regions. And that's why sickle cell disease, which is when you have both of your genes have the mutation in America is found [00:16:00] almost entirely in the African American population. Speaker 4:So about a hundred thousand Americans, again, almost all African American had the disease in the country as a whole and I think 10,000 in California. So it's actually quite a lot of people close. Are you to a cure? I'd like to think we're pretty close. We, we, we haven't moved towards the clinic yet. I'm hoping that one of us will be able to start trials within the next two or three years. But there are other strategies for treating sickle cell disease that are more indirect, that are already in clinical trials using gene editing. [00:16:30] How are those different from what you're doing or our approach at IGI is to directly correct the mutation so we know exactly where the mutation is and we've known it for 70 years. But as I mentioned, just because you know where something is in the word document doesn't mean you could fix it until now. Speaker 4:What our approach is is to make a cut at the mutation and then supply replacement sequence. The replacement sequence is a short piece of DNA. So in order to cause a lasting alteration to your, to the genetics of your blood cells, we actually have to edit your bone marrow cells. [00:17:00] So we take bone marrow cells from patients that have sickle cell disease and then we, this is all in the labs. So we're working this Albridge called ex Vivo or in the lab we cut at the [inaudible] at the mutated region using cas nine and then we supply a short piece of DNA that has the corrected sequence in it. So it just doesn't have any grow. Yeah. And so that will get incorporated in some fraction of the cells. We generally get about 20 to 30% in view in vitro. Then you let the cells grow, then we just analyze them. Speaker 4:So we'll differentiate them into red blood cells and see if they still have sickling [00:17:30] properties. We'll look at their, their gene expression, um, viability, all sorts of, you know, in vitro and points. The other thing we do is that we will edit the cells and inject them into a mouse carrier where the cells will live for months and months and months and then take the cells out of the mouse four months later to see if they still have enough editing to cure the disease. And so none of this goes back into people. Now, the way it would eventually work, if you actually were doing this in a clinical setting, is that you would take a fraction of a patient of a sickle patients bone marrow. You would correct [00:18:00] it using the same exact technique that we're using, but at a much, much larger scale, like we're doing a hundred thousand to a million cells. Speaker 4:You'd be doing more like a billion cells. You would correct the cells, culture them for a day or two in an incubator and then pull them back together and reinfuse them into the patient. Now meanwhile, you would be ablating the patient's bone marrow are using chemotherapy. You can't avoid that. No. What we're hoping is is that if the editing is efficient enough, you don't have to completely ablate the bone marrow, so you don't, you can use a lighter course of chemotherapy, [00:18:30] but you still have to use a certain amount of chemotherapy to get rid of all the remaining uncorrected bone marrow that we just don't have the ability to, to correct that many cells at once. It's just the scale is not practical. So most, um, applications for now for gene editing or gene therapy in general, whether using viruses or, or CRISPR, cas nine or anything else, uh, they generally do this chemotherapy step. Speaker 4:There are many, many groups working on noninvasive methods to do gene editing. So one is to inject a virus that contains [00:19:00] all the stuff you need to make the edit into straight into the compartment that you're trying to treat. So in this case, it would be the, you inject the reagent into the bone marrow, which is painful, but it's a lot better than chemotherapy. Right? Virus is sort of nature's oldest nanoparticle. It's very good at finding cells and putting stuff inside of them. I think we can do better. We can engineer synthetic particles that can do all the same things. They can find the target cell, in this case, a bone marrow stem cell, the cell that leads to all of your other blood cells and they can find them. [00:19:30] And then they can inject all the reagents into that cell specifically and they'll go in and make the edit while the bone marrow cells are still inside your bones. Speaker 4:Um, and that's called Invivo gene editing and that's still very, very much in the early stages. But you know, whether using a viral technique or a nanoparticle technique, you know, from what I've seen in the literature, it's probably only a matter of time. It could be 20 years, it could be 30 years, but you know, it's only a matter of fact. Well, I mean in medical biomedical terms, that's pretty short. You know, when you read the articles, I mean this stuff is all [00:20:00] over the media now and it just sounds so exciting. Like in a couple of years, everything's going to be, these technologies take a very, very, very long time to perfect and try and then get through FDA approval and so on and so forth. A lot of that is just that it takes a lot of time to iron out all of the kinks and biotech. Speaker 4:But what about in other countries won't develop countries? They still don't, they still don't exactly move very quickly. First off, it's hard to prove efficacy. Sometimes it's hard to show that your treatment is actually being effective and you need to try [00:20:30] it. On a whole bunch of people in a whole bunch of different settings and for a whole bunch of reasons and that's just never not going to be really expensive to get the numbers you need to show that something's effective, whether you're the FDA, FDA or anybody else. It's a very expensive process. Getting enough statistical power to do that. You're still talking or thousands of people that you have to test it on and the process is lengthy and expensive. But you know, in my opinion, I think that's all well and good that we have that level of oversight, but it doesn't mean that things take years to really come to fruition and maybe maybe gene editing [00:21:00] might be a little quicker. Speaker 4:There's a lot of very specific problems associated with viral techniques that hopefully we won't have for our approach. I wouldn't be surprised if it took another five or 10 years to really get all the, get all the kinks ironed out. So down the road, what are some of the goals of this research? Monogenetic diseases like sickle cell. The second goal is poly genetic diseases. So this is sort of more of a pie in the sky idea here. We're just beginning to uncover that there are significant genetic contributions to non genetic diseases [00:21:30] to the chances of coming down with a non genetic disease. And I'm speaking specifically about Parkinson's and Alzheimer's. And so we found that there are certain mutations that we're not exactly sure why the sudden mutations that appear to increase your susceptibility to the disease or decrease your subset susceptibility to the disease. Speaker 4:And so that provides a handle for researchers to determine whether or not there is a sort of silver bullet genetic solution to actually curing this disease so that the [00:22:00] patients with these mutations or individuals with these mutations have almost no chance of getting Alzheimer's. Does that mean if I take a person who is, um, coming down with or starting to show signs of Alzheimer's or is at a high risk of Alzheimer's and I introduce this mutation into their, you know, into their tissues, you know, would that cure the disease? Would that essentially short circuit? Would that beat out whatever factors are making them get the disease by providing a different mutation entirely. How do you make that mutation in cells? Well, you should use gene [00:22:30] editing and then make the mutation and then see if all things being equal, that mutation alone can confer resistance to the Alzheimer's phenotype. Speaker 4:That'd be pretty exciting. It is very exciting. So I really think that, I guess as a gene editor or as a hammer looking for a nail, there are a lot more nails, especially in America, developed health system that are non genetic diseases. Are you from California? No, I'm from Boston. Where did you go undergrad? Um, I went to Undergrad at this small liberal arts college [00:23:00] in Portland called Reed College. It's, it's a, it's a fascinating place. Some enormous percentage of Reed college graduates go on to get PhDs. And so after I finished at Reed, I was there for a couple of years and he came down here to get my phd and I stayed on for my postdoc. Now my phd was in something completely different than what I do biophysics. And specifically I studied, um, these proteins that carry materials around your cells called motor proteins. My entire phd was, you imagine a bunch of white dots [00:23:30] on a computer screen moving across the screen, like in a straight line. Speaker 4:That's what I did. I looked at these dots and looked at how fast they're moving. And so I did that for about seven years. And then I just, you know, went to this seminar here, actually the first rewriting genome seminar. It was a, it was a seminar organized by Jennifer Doudna and it had all of the top investigators in gene editing at the time. So I went to the seminar. I was just blown away. I was like, this is so cool. This is just the coolest thing ever. Right? Like I have to do this. I emailed Jennifer, who [00:24:00] is in my building, my old building, Stanley Hall up the hill from here. I'd heard that she was trying to set up this, this organization, this, um, initiative to explore the applications of CRISPR cas nine, whereas her lab is focused on the, the core technology itself, making the technology better. Speaker 4:We would be taking those kinds of innovations and the innovations of others and using it to find applications. Right. And so I was more interested in that, partly strategically thinking, you know, we're going to get past the developing the technology [00:24:30] part pretty soon, but we're going to be exploring applications for hopefully the rest of our careers. So, you know, I thought that was a good decision for a lot of reasons. And so I talked to Jennifer and she said, oh yeah, like yeah, I'm doing it. We need postdocs. She could put me in touch with Jacob Korn, who's the director of IGI who hadn't formally joined yet. Speaker 2:And IGI is again Speaker 4:the innovative genomics initiative. The research lab is about 15 people. It's going to get a little bit bigger and then, but as you had just lots of other stuff, IGI also does some outreach. [00:25:00] The most inefficient thing we've done yet is we host a workshop. So we invite scientists from all around the community, ideally scientists that don't work in the field of gene editing, but want to try it out. Not just scientists or doctors, but also, you know, policymakers. And Speaker 2:there is a reason to make sure that it stays in the right hands. Yes there is. Does anything scare you about it at all? I mean, you're right in the heart of it, Speaker 4:you know, you think of bad actors and things like that. Although again, whether we're happy about it [00:25:30] or not, humanity has invented a whole host of really dangerous bad things from nuclear weapons to infectious agents to chemical weapons, weapons of mass destruction. And you know, we're all still here. It's, I guess what I mean. Should there be any controls on the use of the technology for research compared to other technologies like I don't think so. Should we be very careful about, well, what if someone wanted to do something not so good with this method that I'm outlining in publishing in a paper, [00:26:00] right? I mean, yes, we should. And that's exactly why we, I think should be very careful about germline editing. And again, that's why at IGI we're really focused on more traditional therapeutic editing. Speaker 2:Yeah, you're lucky that Jennifer is a big part of that because you know, she is a vocal person about the ethics involved. Here's a short segment from a Ted talk that she gave recently. Together with my colleagues, I've called for a global conversation about the technology that I co-invented so that we can consider all of the ethical [00:26:30] and societal implications. Imagine that we could try to engineer humans that have enhanced properties such as stronger bones or less susceptibility to cardiovascular disease, good eye color, or not to be taller designer humans, if you will. Right now, the genetic information to understand what types of genes would give rise to these traits are mostly not known, but it's important to know that the CRISPR technology gives us a tool to make such [00:27:00] changes. Once that knowledge becomes available, this raises a number of ethical questions that we have to to carefully consider. Speaker 2:This is why I and my colleagues have called for a global pause in any clinical application of the CRISPR technology in human embryos to give us time to really consider all of the, the various implications of of doing so. This is no longer science fiction, genome engineered animals and plants are happening right now. And this puts in front of all of us [00:27:30] a huge responsibility to consider carefully both the unintended consequences as well as the intended impacts of a scientific breakthrough. So mark, what would you like to see happen in this space in the near future? Speaker 4:Suddenly, I'm thinking about a lot lately is that this idea of personalized gene editing. You can imagine a world in which you go into the doctor, they sequence your genome, they see if there's anything that needs fixing [00:28:00] and then they put it in order for the reagent that can be synthesized custom to whatever specifications. So it can go into whatever Oregon you want, whatever cell type you want and program any genetic change you want based on your own genetic sequence. You then go into the doctor's office and they put something into your arm and they infuse you with that reagent and then it starts to make the change. It's certainly our approach with sickle cell, you know, points in that direction. The reasons that we're using are simple. They're easily customizable. [00:28:30] Um, you don't have to have a lot of it on hand. You can produce it in a factory instead of having to grow it from cell culture. Speaker 4:I imagine that future, this far off future in which we have sort of live in this almost Saifai type world where you know, you can make any genetic manipulation you want or your doctor candidly, you know, in the doctor's office, no surgery, no surgery, no nothing. Well then I think about, so what am I doing today that's going to nudge the, the rock a little bit further up the hill in that direction? Where do I want things to be in 20 years and what can I do [00:29:00] to go there? We'll see how I do, right? I mean, I'm still just a postdoc, but I think it really, really helps to think about like what's the La crazy, crazy far off like vision for what you're doing? Like how, how could it totally change the world? And it's important to think about that when you're at the lab bench. Speaker 4:You know, whether you're in a classroom lab at bio one a or whether you're in my research lab, what am I doing to bring that out? That longterm vision. It's so easy to lose track [00:29:30] of where you're going in the day to day, especially as a scientist, because as researchers we have, our head is filled with innumerable minutiae of our day to day experiments that just all we ever think about, and sometimes you need to step back and be like, what am I really doing? That's a characteristic, certainly of the most successful entrepreneurs and probably the most successful scientists as well. Speaker 3:Well, mark, you've helped us understand some very complicated ideas. I've been talking with Mark Dewitt. He is a biophysicist and a lab member of the innovative genomics [00:30:00] initiative here on campus at Lee Kushing center for Genomic Engineering. Thanks again for being on this program and talking about a very difficult and complex subject of gene editing. Thanks for having me. You've been listening to method to the madness. We'll be back again in two weeks is the same. I'm Speaker 1:telling you. See acast.com/privacy for privacy and opt-out information.

In 2013, Before California's initiative requiring utilities to install 1,325 MW of energy storage, the market was just in test phases. But now, the market has really heated up and energy storage competes with other sources of energy. Mike Hopkins, CEO of Ice Energy, gives his perspective on the state of the market in California--and the contracts his company has won.

We talk technology and law with Kevin Collins and begin with the law of the horse. The Supreme Court has given us decisions about searching cell phones, tiny antennae and broadcast television, and patents on business methods implemented in software. Molecules, hair-drying calculating machines, DNA, and the meaning of knowledge. It’s an IP festival this week. This show’s links: Kevin Collins’ faculty profile and writing Edinburgh’s statue of Adam Smith, though not the photo taken by listener Barbara: Riley v. California, the cell phone search case, PDF and HTML Frank Easterbrook, Cyberspace and the Law of the Horse Lawrence Lessig, The Law of the Horse: What Cyberlaw Might Teach Christian Turner, The Information Law Crisis Sony Corp. v. Universal City Studios, Inc., the VCR case American Broadcasting Cos. v. Aereo, PDF and HTML Mike Masnick, Aereo Fallout Begins: Fox Uses Ruling To Attack Dish's Mobile Streaming Service Summary of the history of cable television in the U.S. Alice Corp. v. CLS Bank, PDF and HTML Episode 3: Cut It Off (guest Paul Heald) O’Reilly v. Morse, the telegraph case Nautilus v. Biosig Instruments, PDF and HTML Association for Molecular Pathology v. Myriad Genetics Kevin Collins, The Knowledge/Embodiment Dichotomy Kevin Collins, Bilski and the Ambiguity of 'An Unpatentable Abstract Idea’ Michele Boldrin and David Levine, Against Intellectual Monopoly Michele Boldrin and David Levine, The Case Against Patents Special Guest: Kevin Collins.