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Jasper Therapeutics launches out of Stanford with new approach to stem cell treatment – Endpoints News

The first girl in the trial came in with chronic diarrhea and the immune system of an untreated HIV patient. Born with a rare genetic disease that impeded her ability to make B and T cells, she had once been given a stem cell transplant but it didnt take. Back in the hospital, she was injected with a new experimental antibody and then given a new stem cell transplant. Soon, she gained weight. The diarrhea stopped.

She has normal T cells now, Judith Shizuru, the Stanford scientist who pioneered the antibody, told Endpoints News. Shes in school.

Its the kind of medical story to launch a biotech around, and thats what Shizuruis doing. Today, her company Jasper Therapeutics is emerging out of stealth-mode with $35 million in Series A funding led by Abingworth and Qiming, a molecule from Amgen, and a Phase I trial set for its first readout on Monday at ASH.

Jasper is broadly aimed at making stem cell transplants safer, more accessible and more effective by using antibodies as conditioning agents. Theseagents clear out bone marrow to make room for the new stem cells to graft onto the body.

Their Phase I uses a naked antibody called JSP191 to help patients with severe combined autoimmune deficiency receive stem cell transplants the only possible cure for the life-threatening disease but such transplants are used in a wide variety of conditions and Jasper has broader aims. Those include other autoimmune diseases, acute myeloid leukemia and cell-directed gene therapy.

Theres a significant amount of progress being made in gene therapy, interim CEO William Lis told Endpoints, but no progress being made in a conditioning agent that will help graft gene therapy.

Shizuru path to the new antibody was long and fortuitous. In 1987, Arl Arzst, the legendary ad executive and president of Proctor and Gamble international flew in on a recruiting trip for Stanford business students. There he visited Shizuru, a young biologyPhD candidate, because he knew her roommate. Arzsts daughter had diabetes and as Shizuru explained the work she was doing on pancreatic islet cell transplants, he told her to come to Europe.

Shizuru had never been to Europe, but there Arszt introduced her to Ken Farber and the other founders of the Juvenile Diabetes Foundation (now the JDRF). The founders struck a years-long correspondence and encouraged Shizuru to go to medical school, where she decided that if scientists were ever going to develop transplants that didnt trigger an immune response, it would be through stem cell work. She continued her work at the Irv Weissman Stanford regenerative lab, where eventually a graduate student made a discovery that piqued her interest.

To put new stem cells in, you have to get the old stem cells out. Thats not always easy. The cells sit inthese pockets in the bone marrow, and theyre pretty comfortable there. Doctors have to force them out, often using chemotherapy or radiation, which damage DNA and cause severe side effects. The costs sometimes outweigh the benefits.

There are diseases were not treating because its too dangerous, Shizuru said. And the kids were treating, theyre so, so fragile.

The grad student had shown in mice that antibodies could be used to deplete the stem cells and potentially eliminate the need for chemotherapy or radiation. Shizuru and her team began looking to see if anyone had developed a human version of the antibody, CD117. It turned out Amgen had already developed a version of this antibody for a different use. It also turned out she had a former postdoc and a former advisor who worked there. They began a collaboration.

We set out to cross the valley of death, Shizuru said, using an industry slang term for the jump from animal models to human uses.

After making a variety of tweaks to the treatment, they published a paper inScience Translational Medicine in 2016showing the antibodies created a 10,000 fold reduction in the number of stem cells in mice.

The same year, they began a clinical trial on 90 SCID patients. These patients had received stem cell transplants when they were very young but hadnt been given chemo or radiation for fear the side effects would be too severe. The original transplants boosted their numberof immune cells, but without chemo or radiation, the stem cells dont graft into those pockets and the body wont continue producing T cells. Without those, they are extraordinarily prone to infection. Many pass away before age 2.

The hope is that the antibodies allowed the stem cells to graft, and the preliminary answer to that question will be out on Monday. For the first girl in the trial, life has improved but questions about how long her body will make immune cells remain. Still, for that girl and others, Shizuru is confident.

We see there is stem cell engraftment, Shurizi said. They are actually making new T cells.

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Jasper Therapeutics launches out of Stanford with new approach to stem cell treatment - Endpoints News

MaaT Pharma Announces the Presentation of Positive Data with Its Lead Microbiome Biotherapeutic in Intestinal-Predominant Acute…

MaaT Pharmas full-ecosystem microbiota biotherapeutic provided positive impact with satisfactory safety profile in eight patients with advanced stages of GI aGvHD

MaaT Pharma announced today that leading hemato-oncological experts presented clinical data on the compassionate use of MaaT Pharmas lead full-ecosystem microbiome restoration biotherapeutic, MaaT013. The data included eight patients that developed gastrointestinal-predominant, acute Graft-versus-Host-Disease (GI aGvHD) after receiving an allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) to treat their hematologic malignancies. All patients were positively impacted by the MaaT013 treatment, with three patients achieving complete response. GvHD, a condition where the transplant donors immune cells attack the patients tissues, is one of the most serious complications of allo-HSCT, and its acute GI form is fatal in most cases. MaaT013 features a consistently high diversity and richness of microbial species in their natural environment. It aims to restore the symbiotic relationship between microbes in the gut and the immune system of the patient to correct the responsiveness and tolerance (homeostasis) of immune functions and thereby contain GI GvHD. The results were presented in a poster presentation on December 7, 2019 during the 61st American Society of Hematology (ASH) Annual Meeting and Exposition held in Orlando, Florida.

"The GI aGvHD patients who were treated with MaaT013 had a very poor prognosis with no other therapeutic options. The results following MaaT013 administration showed a positive impact on all patients," commented Professor Mohamad Mohty, MD, PhD, Head of the Hematology and Cellular Therapy Department at Sorbonne University, Saint Antoine Hospital in Paris. "The most impressive results were seen in those patients who achieved a complete response and who were able to taper and stop using steroids and other immunosuppressants without relapse of gastrointestinal symptoms."

In the presented evaluation, eight patients with a median age of 67 were treated for classical aGvHD, late-onset aGvHD or aGvHD with overlap syndrome that were either steroid-resistant or steroid-dependent following stem cell transplantation. These patients had previously been treated with and failed up to five lines of systemic therapy for aGvHD. Each patient received at least one and up to three doses of MaaT013 and treatment response was evaluated seven days after each administration and on day 28 after the first dose. Based on the best response to the treatment, all eight patients experienced at least a partial response with three patients achieving complete response, two patients with very good partial response and three patients with partial response. Overall, the data demonstrated that reintroduction of a full-ecosystem microbiota provided therapeutic effect and was tolerated in a satisfactory manner in these patients.

Herv Affagard, Co-founder and CEO of MaaT Pharma added, "We provided our cGMP-manufactured lead biologic drug, MaaT013, to hospitals as part of a compassionate use program to give GI GvHD patients a therapeutic option where there are no other available treatments after steroids and additional lines of treatment. These findings indicate that reestablishing the gut microbiome improved outcomes in these patients."

Moreover, MaaT Pharma is currently conducting the HERACLES Phase II clinical trial (NCT03359980) to evaluate the safety and efficacy of MaaT013 in steroid-refractory, GI aGvHD patients, with more than half of the patients enrolled.

To date, a total of 46 patients with GI GvHD have been treated with MaaT013, including patients under compassionate use and patients enrolled in the Phase II clinical trial. MaaT Pharma is actively developing an oral formulation of MaaT013 (a capsule, MaaT033) to provide easier administration for patients while delivering a similar effect of regenerating the microbial ecosystem with the goal of restoring immune homeostasis in the gut.

The poster can be viewed on the companys website under "News".

About HERACLES

The HERACLES study is a multi-center, single-arm, open-label study, enrolling 32 patients to evaluate the efficacy and safety of MaaT Pharmas lead microbiome restoration drug candidate, MaaT013, in steroid-resistant, gastrointestinal-predominant aGvHD patients. Acute GvHD is a serious, often fatal syndrome typically involving the gut, skin, and liver. Treatments up to now focused largely on suppressing the immune reaction that is induced by the donor cells derived from the hematopoietic stem cell graft reacting against the host. These strategies have remained clinically unsuccessful in most cases, with mortality rates around 80% after twelve months in steroid-resistant cases. Patients with hematological malignancies receive multiple courses of chemotherapy, antibiotics, and ultimately conditioning before HSCT, which are known to severely impact the gut microbial composition.

Story continues

About MaaT013

MaaT013 is the first full-ecosystem, off-the-shelf, reproducible, enema formulation manufactured using MaaT Pharmas integrated Microbiome Restoration Biotherapeutic (MMRB) platform. The product has a stability of up to 24 months and is characterized by a high diversity and consistent richness of microbial species derived from pooled healthy donors and manufactured at the companys centralized European cGMP production facility. MaaT013 has been granted Orphan Drug Designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and is already being administered in compassionate use.

About MaaT Pharma

MaaT Pharma, a clinical stage company, has established the most complete approach to restoring patient-microbiome symbiosis to improve survival outcomes in life-threatening diseases. Committed to treating blood cancers and Graft-versus-Host-Disease, a serious complication of allogeneic stem cell transplantation, MaaT Pharma has already achieved proof of concept in acute myeloid leukemia patients. Supporting the further expansion of our pipeline into improving outcomes of immunotherapy in solid tumors, we have built a powerful discovery and analysis platform, GutPrint, to evaluate drug candidates, determine novel disease targets and identify biomarkers for microbiome-related conditions. Our biotherapeutics are produced under the strictest cGMP manufacturing and quality control process to safely deliver the full diversity and functionality of the microbiome. MaaT Pharma benefits from the commitment of world-leading scientists and established relationships with regulators to spearhead microbiome treatment integration into clinical practice.

View source version on businesswire.com: https://www.businesswire.com/news/home/20191207005042/en/

Contacts

For MaaT Pharma Herv Affagard, CEOPhone: +33 4 2829 1400E-Mail: haffagard@maat-pharma.com

Media Requests for MaaT Pharma Dr. Stephanie May or Dr. Jacob VergheseTrophic CommunicationsPhone: +49 89 23 88 77 30 or +49 171 185 56 82E-Mail: may@trophic.eu or verghese@trophic.eu

Link:
MaaT Pharma Announces the Presentation of Positive Data with Its Lead Microbiome Biotherapeutic in Intestinal-Predominant Acute...

Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers – GlobeNewswire

AUTO1 shows 87% MRD negative complete response in adult patients with r/r ALL, with no severe cytokine release syndrome

Data presented at 61st American Society of Hematology Annual Meeting form basis for advancement of AUTO1 into pivotal clinical trial in adult ALL

Investor call to be held December 9 at 8:30 am ET / 1:30 pm GMT to review data

LONDON, Dec. 07, 2019 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc(Nasdaq: AUTL) announced today new data highlighting progress on its next-generation programmed T cell therapies to treat patients with acute lymphoblastic leukemia (ALL) and adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data were presented in oral presentations at the 61stAmerican Society of Hematology(ASH) Annual Meeting and Exposition inOrlando, FL. Additional data on pediatric patients with ALL will be presented on December 8.

The data on AUTO1 presented at this years ASH meeting demonstrate the favorable safety profile and high level of clinical activity of AUTO1 in both adults and pediatric patients with ALL, and we look forward to initiation of the pivotal program in adult ALL in the first half of 2020, said Dr. Christian Itin, chairman and chief executive officer of Autolus.

Acute Lymphoblastic Leukemia Data Presented

Title: AUTO1 A novel fast off CD19CAR delivers durable remissions and prolonged CAR T cell persistence with low CRS or neurotoxicity in adult ALL (Abstract # 226)

Updated results for ALLCAR19, the Phase 1 trial evaluating AUTO1 in adults with recurrent/refractory ALL, were presented by Dr. Claire Roddie MB, PhD, FRCPath, honorary senior lecturer,Cancer Institute, University College London (UCL), in an oral presentation. The trial is designed to assess the primary endpoints of safety ( Grade 3 toxicity) and feasibility of product generation, as well as other secondary endpoints, including efficacy. The trial enrolled patients with a high tumor burden (44% had 50% BM blasts), who were considered high-risk for experiencing cytokine release syndrome (CRS). Product was manufactured for 19 patients; product for 13 of those patients was manufactured using a semi-automated closed process, which will be used for commercial supply.

As of the data cut-off date of November 25, 16 patients had received at least one dose of AUTO1. AUTO1 was well tolerated, with no patients experiencing Grade 3 CRS, and 3 of 16 patients (19%), who had high leukemia burden, experiencing Grade 3 neurotoxicity that resolved swiftly with steroids.

Of 15 patients evaluable for efficacy, 13 (87%) achieved MRD negative CR at 1 month and all patients had ongoing CAR T cell persistence at last follow up. CD19-negative relapse occurred in 22% (2 of 15) patients. In the patients dosed with AUTO1 manufactured in the closed process, 9 of 9 (100%) achieved MRD negative CR at 1 month and 6 months event free survival, and overall survival in this cohort was 100%.

Adult ALL patients, who face a median survival of less than one year after their ALL recurs or relapses, have a significant need for a CAR T cell therapy that is highly active, safe and is a standalone therapy not requiring a stem cell transplant, said Dr. Hagop M. Kantarjian, Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

The novel CD 19 CAR-T therapy, AUTO1, is potentially transformative as a standalone curative option for patients with r/r ALL, especially in adults, given its favorable safety profile, said Dr. Max Topp associate professor of Internal Medicine, Hematology and Oncology at the University of Wuerzburg.

Title: Therapy of pediatric B-ALL with a lower affinity CD19 CAR leads to enhanced expansion and prolonged CAR T cell persistence in patients with low bone marrow tumor burden, and is associated with a favorable toxicity profile (Abstract # 225)

Dr. Sara Ghorashian, honorary senior lecturer, Great Ormond Street Institute of Child Health, University College London, presented updated data from the phase 1 CARPALL study of AUTO1 in pediatric ALL patients with low bone marrow tumor burden. The trial is intended to assess the primary endpoints of safety and proportion of patients in molecular complete remission at 1 month. The study recruited a total of 25 patients and stratified them into 2 cohorts. Fourteen patients were treated in cohort 1, which utilized a manual manufacturing process; product was unable to be generated in 3 patients. Median follow-up was 27 months in cohort 1. Seven patients were treated in cohort 2, which utilized the semi-automated closed manufacturing process, which will be used for commercial supply. The aim of cohort 2 was to demonstrate feasibility of manufacture at scale. Product was generated for 100% of patients. Median follow-up was 7 months in cohort 2.

AUTO1 was well-tolerated overall, with no patients experiencing Grade 3 CRS and 1 of 21 (5%) experiencing Grade 4 neurotoxicity, which was considered unrelated to CAR T therapy.

Nineteen of 21 treated patients (90%) achieved molecular complete remission at 1 month post infusion. Consistent with pre-clinical data, CAR T cell expansion was excellent and detectable by flow in a number of patients up to 36 months. Persistence was noted in 15 of 21 patients at last follow-up, up to 36 months. In cohort 2, 100% of patients achieved molecular complete remission at 1 month post infusion.

In the 14 patients in cohort 1, the overall survival at 6 months was 86% and at 12 months was 71%; event free survival (EFS) at 6 months was 71% and at 12 months was 54%. The patients in cohort 2 are not yet evaluable for these parameters. Overall, nine patients relapsed; 5 of 8 evaluable relapses were due to loss of CD19 antigen on the tumor cells.

Title: Clonal dynamics of early responder and long-term surviving CAR-T cells in humans (Abstract # 52)

Dr. Luca Biasco, senior research associate at University College London, presented a detailed analysis of CAR T products, and insertion site analysis from the CARPALL phase 1 patients. This analysis revealed highly polyclonal engraftment, even at very late time-points. Dr. Biasco hypothesized that the propensity for high level polyclonal long-term engraftment was due to favorable phenotype of the CAR T product and the binding kinetic of the receptor.

Diffuse Large B-cell Lymphoma Data Presented

Title: Phase 1/2 study of AUTO3, the first bicistronic chimeric antigen receptor (CAR) targeting CD19 and CD22 followed by an anti-PD1 in patients with relapsed/refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL): Results of cohort 1 and 2 of the ALEXANDER study (Abstract # 246)

Dr. Kirit Ardeshna, consultant hematologist, Department of Hematology, University College London Hospital NHS Foundation Trust, presented updated data from the ALEXANDER Phase 1/2 study of AUTO3, the first bicistronic CAR T targeting CD19 and CD22 followed by an anti-PD1, in diffuse large B cell lymphoma (DLBCL). 16 patients were treated, and fourteen patients were evaluable at one month. AUTO3 was well-tolerated, with no patients experiencing Grade 3 CRS with primary treatment, and 1 of 14 experiencing Grade 3 neurotoxicity that resolved swiftly with steroids. Five of 14 had a complete response, with 4 of 5 complete responses ongoing, the longest at 18 months.

DLBCL is an aggressive and rapidly progressing cancer, and early response is critical to ensuring positive outcomes for these patients. These early data show the promise of AUTO3 in DLBCL, and we expect to advance AUTO3 to a decision point in relapsed/refractory DLBCL by the middle of next year, said Dr. Christian Itin, chairman and chief executive officer of Autolus. In addition, we look forward to presenting the data from the AMELIA trial of AUTO3 in pediatric ALL during poster sessions on Sunday, December 8, 6:00 8:00 PM ET.

Investor call to review data on Monday, December 9

Autolus management will host an investor conference call on Monday, December 9, at 8:30 a.m. EDT/ 1:30pm GMT, to review the data presented at ASH.

To listen to the webcast and view the accompanying slide presentation, please go to:https://www.autolus.com/investor-relations/news-and-events/events.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 9796038. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 9796038.

About AUTO1

AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety - while maintaining similar levels of efficacy - compared to current CD19 CAR T cell therapies.Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells' abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights fromUCL Business plc(UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 studies, one in pediatric ALL and one in adult ALL.

About AUTO3

AUTO3 is a programmed T cell therapy containing two independent chimeric antigen receptors targeting CD19 and CD22 that have each been independently optimized for single target activity. By simultaneously targeting two B cell antigens, AUTO3 is designed to minimize relapse due to single antigen loss in patients with B cell malignancies. AUTO3 is currently being tested in pediatric ALL in the AMELIA clinical trial and in diffuse large B cell lymphoma in the ALEXANDER clinical trial.

AboutAutolus Therapeutics plc

Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information please visit http://www.autolus.com.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus financial condition and results of operations, as well as statements regarding the anticipated development of Autolus product candidates, including its intentions regarding the timing for providing further updates on the development of its product candidates, and the sufficiency of its cash resources. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed on November 23, 2018 as well as discussions of potential risks, uncertainties, and other important factors in Autolus' future filings with the Securities and Exchange Commission from time to time. All information in this press release is as of the date of the release, and the company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Investor and media contact: Silvia TaylorVice President, Corporate Affairs and Communications Autolus+1-240-801-3850s.taylor@autolus.com

UK:Julia Wilson+44 (0) 7818 430877j.wilson@autolus.com

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Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers - GlobeNewswire

Sickle Cell Anemia Patient Becomes First Person in the US to Have Her Genes Edited With CRISPR – Interesting Engineering

Last week, a woman namedVictoria Gray became the first person in the U.S. to have her cells edited with CRISPR. The41-year-old patient was sufferingfromsickle cell anemia.

RELATED:FIRST HUMAN TRIAL USING CRISPR GENE-EDITING IN US BEGINS

The condition, caused by a genetic mutation that messes with the shape of red blood cells, causes havoc on patients, and to make things even worse, the options for treatment are very limited and ineffective. The only current treatment for sickle cell anemia patients is a donor transplant that works for just 10% of patients, but all that is about to change.

It was clear that analternative, much more effectivesolutionwas desperately needed. After much consideration, doctors believed that editing cells extracted from a patient's own bone marrow could restore effective red blood cell creation, and this is exactly the operation they attempted on Gray.

The doctors used CRISPR to tweak Gray's bone marrow DNA to turn on a specific protein that would allow proper red blood cell generation. The operation makes Gray the first person in the U.S. to undergo a CRISPR editing procedure and the second globally.

The treatment comes from observations made back in the 1940s.In 1941 a pediatrician named Jane Watson noticed that babies with sickle cell didnt have symptoms until 6 months to 1 year of age, Vivien Sheehan, a hematologist at Baylor University told Popular Science.

The pediatrician also discovered that these infants produced fetal hemoglobin for much longer periods than healthy babies.Following Watson's observations, the research since then has indicated that increasing fetal hemoglobin could provide an effective treatment for the disease.

Now, CRISPR may just make that treatment viable. But before we get too excited, it should be noted that the strategy comes with several risks.

In order for the edited cells to be inserted back into the patients bone marrow, other stem cells need to be deactivated. Otherwise, there is the chance the unedited stem cells may continue to produce sickled red blood cells very fast, outpacing the edited cells' production of healthy cells.

Now researchers say they need to follow Gray's progress for at least 15 years to rule out any other potential dangers of the procedure. Still, for those 90% suffering with sickle cell anemia that don't respond well to current treatment, the procedure, if successful, would offer the much-needed lifeline they've been hoping for.

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Sickle Cell Anemia Patient Becomes First Person in the US to Have Her Genes Edited With CRISPR - Interesting Engineering

Teen diagnosed with cancer again just months after being told he beat disease – Mirror Online

A teenage boy has been diagnosed with an aggressive cancer again just four months after a doctor told him he had beaten the devastating disease.

There is just a 10 per cent chance that chemotherapy will work this time for 17-year-old Jacob Fradgley, who is "wasting away", his heartbroken mum said.

The teen, from Skegby in Nottinghamshire, originally found out that he had metastatic Ewing sarcoma, a rare form of bone cancer, when he was just 15 in May 2018.

After a "whirlwind" year of treatment, including 19 rounds of chemotherapy and 56 sessions of radiation therapy, Jacob was classed as cancer free in July, his mum, Sammy Fradgley, 34, told NottinghamshireLive.

But they were given the heartbreaking news that his cancer had returned after his mum found a lump on his head just weeks before Christmas.

Jacob was diagnosed with a relapse of metatistic ewing sarcoma, which affects bones and bone tissue.

Only 30 children a year are diagnosed in the UK.

Miss Fradgley has launched a campaign to fulfil some of her son's wishes - including meeting ex-soldier Ant Middleton SAS: Who Dares Wins - after doctors told her that if there was anything he wanted to do he should "do it now".

After his mum found the lump, Jacob was taken to Queen's Medical Centre in Nottingham for a CT scan.

He underwent surgery to remove the tumour in his head a week later.

Doctors then found more tumours in his head, hip and knees.

Miss Fradgley, a senior carer, said: "It took me two weeks to accept it.

"There's not a lot out there to treat a relapse, and we're just getting further away from solutions.

"There's around a 10 per cent chance the chemotherapy will work this time.

"You never think it's going to come back but I've just got to support him now."

Jacob had his final round of radiation therapy in January and his last round of chemo on New Year's Eve.

In the following months he took medication to prevent the cancer returning.

His mum said: "He was able to go to his prom, he was going to cadets and studying Public Services at Vision West Notts College.

"But three weeks ago I was touching his hair, and felt the lump. It all just happened so quick.

"Now its more or less the same thing. It's so aggressive and is known for coming back."

She added: "It has upset him, that he has to go through it all again.

"He has to have six rounds of chemotherapy and the doctors also want to harvest stem cells. If the chemo works, he may be able to go for stem cell treatment."

Jacob's consultant has told her that if there was something he wanted to do he should "do it now".

She has launched a JustGiving campaign to raise enough money so Jacob can create memories with his six-year-old sister Leah.

It has raised more than 2,300 so far.

Miss Fradgley said: "I just don't want to say no. I want to give him everything he wants.

"It's so hard to just watch him wasting away in front of me, but I am trying to do everything I can for him.

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"He does still smile, but I am also there when he gets upset.

"His biggest aspiration is to drive a tank, meet Ant Middleton - anything to do with the army.

"His favourite colour is red so I have also started a 'Going Red for Jacob' campaign and I plan to make red bands with 'Team Fradgley' so everyone can support him and donate."

Barbera White, founder of the When You Wish Upon a Star charity, which is supporting the family, said: "I just wanted mum to know if there's anything we can do, we will try.

"I am trying to arrange a wish for him and I am currently working on something that I know he wants.

"Even after 30 years of the charity, I keep in touch with the families I meet, and we all want to help create some memories for Jacob."

Last December, the charity gave Jacob, his mum and his sister a trip to Lapland as he battled cancer.

At the time, he was looking forward to spending Christmas out of hospital and said the Lapland trip was a chance to "be together like a normal family".

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Teen diagnosed with cancer again just months after being told he beat disease - Mirror Online

Living with cancer: ‘Exercising during my chemotherapy treatment worked wonders’ – inews

NewsReal LifeCathal Morrow, 54, talks about the positive effects running and gym sessions had on him both physically and mentally

Friday, 6th December 2019, 5:33 pm

As part of a new series calledLiving with cancer,iis sharing people's stories about how the disease affects their life and relationships, both practically and emotionally.

Cathal Morrow knew that he could have easily have slumped into a depression after hearing the dreaded C word.

When he began his three month chemotherapy treatment, it knocked him for six. "The first 10 days I lay in bed watching Netflix. I felt rotten, exhausted and sick. I felt like I'd been hit by a bus. I thought oh gosh, I've got three months of this."

Then his youngest son had what he calls a post-traumatic stress disorder (PTSD) episode, and Cathal had to physically restrain him. It made him realise he was stronger than he had realised. And so, from then, he forced himself to turn off the telly and go outside a trip to the shops or a stroll around the park.

"I was knackered afterwards, but it felt good," he said. Having quit smoking when he was diagnosed with T-Cell Lymphoma, a type of blood cancer, he decided to go to the gym. It felt good, so the next day he went for a run, and managed 6 km (3.7 miles), and the next day pounded the pavements again.

Cathal had run a marathon a decade ago, but had stopped running regularly. The 54-year-old soon built up his fitness and took on a half marathon (21 km/13.1 miles) while still having chemo.

Exercise can help general health, and there's been a recent paradigm shift with regards to the role it plays in cancer patients. Last year, leading experts on cancer called for exercise to be prescribed to all cancer patients, alongside traditional treatment, and say not to do so would be harmful.

If the effects of exercise could be encapsulated in a pill, it would be prescribed to every cancer patient worldwide and viewed as a major breakthrough in cancer treatment, Professor Prue Cormie from the Australian Catholic University wrote on The Conversation.

'It stops me from becoming a miserable sod'

Cathal began exercising five times a week, and he says it helped empower him to move out of a more passive patient role, and improved not just his well-being but his attitude, too.

"It would be easy to think, I'm sick, I'm having treatment, so I must wrap myself up in cotton wool. Doing the half-marathon, I was shouting 'Fuck cancer' as I hauled myself up a gruesome hill. It was my way of sticking my finger up to the disease. It worked wonders.

"Running helped me manage my fear of dying. There's no two ways about it, it's terrifying to be told you have cancer. I had a good cry, then I thought right, I'm beating this. Exercise was a way to channel my frustration, at times rage.

"It gave me something to look forward to almost every day, something very immediate to focus on that I could achieve. It made me feel at least partly in control of my health.

"It's also had a positive effect on my two sons. They saw I was fighting cancer, that I refuse to give in. It stops me from becoming a miserable sod, because I dont need to fake positivity."

Rest is 'counterproductive'

Macmillan Cancer Support also say that traditional advice for combating fatigue centering on energy conservation is "counterproductive", since "excessive rest worsens treatment-related loss of physical function".

'Studies have found exercise during treatment can actually change the tumor microenvironment and trigger stronger anti-tumor activity'

Mayo Clinic experts

The charity states: "This can lead to a vicious cycle of accumulating fatigue and deteriorating function. A promising body of evidence indicates that an appropriate balance of physical activity alongside rest during treatment periods helps to control fatigue and maintain physical function."

Experts at the Mayo Clinic say as well as reducing depression and anxiety, exercise can reduce pain. They point out "studies have found that exercise during treatment can actually change the tumor microenvironment and trigger stronger anti-tumor activity in your immune system". And animal studies have found that exercise can lead to tumor reduction in rodents.

Physical activity also helps you manage your weight, which is an important cancer risk factor and has been linked to higher risk of cancer recurrence.

'Balance is key'

Cathal, from Wimbledon, London, says exercise made him feel better prepared physically to be able to handle the treatment. His doctor approved of him getting active, but warned him not to overdo it.

Cathal, who works in PR and as a writer, underwent stem cell treatment last November, and has since gone into remission, although he still struggles with fatigue.

"My doctor is fully supportive of me exercising my way through chemo although she cautioned me not to 'go mental'. I probably did a bit. I just love pushing my body past what I think is possible. It's felt fantastic feeling the fittest I've been in a decade.

"But I think it's also important to listen to you body, balance is key. I aimed to exercise five times a week but if I felt rubbish I'd rest. Same goes for the emotional side. Sometimes you have to succumb to not feeling very positive. Some days I feel too crap to do anything and spend a few days in bed."

Cancer Research says how much and how intense a cancer patient should exercise will depend on the individual, and advises people check with their doctor beforehand. You can read their guidelines about exercising when you have cancer here.

Do you have a personal story? Email claudia.tanner@inews.co.uk

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Living with cancer: 'Exercising during my chemotherapy treatment worked wonders' - inews

Takeda to Present Results from the Phase 3 TOURMALINE-AL1 Trial of NINLARO in Patients with Amyloidosis – Business Wire

CAMBRIDGE, Mass. & OSAKA, Japan--(BUSINESS WIRE)--Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) today announced that results of the TOURMALINE-AL1 trial will be presented during an oral session at the 61st American Society of Hematology (ASH) annual meeting on Saturday, December 7, 2019 in Orlando, Florida. TOURMALINE-AL1 is a Phase 3, randomized clinical trial evaluating the effect of NINLAROTM (ixazomib) in combination with dexamethasone in patients with relapsed or refractory systemic light-chain (AL) amyloidosis.

The TOURMALINE-AL1 trial did not meet the first of the two primary endpoints of significant improvement in overall hematologic response, as reported in June 2019. Hematologic responses were seen in 53% versus 51% of patients receiving NINLARO plus dexamethasone versus physicians choice (odds ratio 1.10 [95% CI 0.60-2.01], p=0.762) as assessed by an Adjudication Committee (AC). The second primary endpoint of two-year vital organ deterioration or death was not mature at the time of analysis. Other endpoints studied including vital organ progression free survival (PFS), hematologic PFS, time to treatment failure and time to subsequent therapy were numerically higher in the NINLARO plus dexamethasone arm compared to the physicians choice arm. Takeda is committed to making data available to researchers to continue investigation of this disease. NINLARO is not approved as a treatment for AL amyloidosis.

AL amyloidosis is a rare condition, for which prognosis and patient outcomes are poor. Current treatments are often retrofitted from therapies used for multiple myeloma, said Angela Dispenzieri, MD, Mayo Clinic, and the trials principal investigator and lead author. For a Phase 3 study that did not meet its primary endpoint, this trial provides interesting information for this community and for future studies. Ongoing research and development to investigate potential treatment options for this underserved patient population is critical.

We look forward to the opportunity to share the data from the TOURMALINE-AL1 trial, said Phil Rowlands, Head of Oncology Clinical Research and Development, Takeda. We are confident that sharing our findings with the community will help encourage conversations around the need for continued research to address the needs that remain in this patient population.

There are serious unmet needs for people living with amyloidosis. AL amyloidosis is a progressive and fatal disease; many patients are diagnosed late, significantly impacting life expectancy. The challenges associated with developing drugs for this disease make continued research and development for treatment critical, said Isabelle Lousada, Founder and CEO of the Amyloidosis Research Consortium. The data from TOURMALINE-AL1 provide valuable insights to researchers as they select endpoints for future amyloidosis studies, and knowledge that will provide context in future drug reviews and approvals, ultimately aiding in providing treatment options for patients.

Primary Results from the Phase 3 TOURMALINE-AL1 Trial of Ixazomib-Dexamethasone Versus Physicians Choice of Therapy in Patients (Pts) with Relapsed/Refractory Primary Systemic AL Amyloidosis (RRAL). Saturday, December 7, 9:30 a.m., Orange County Convention Center, Hall E1.

Key findings, to be presented by Dr. Angela Dispenzieri, include:

About the TOURMALINE-AL1 Trial

TOURMALINE-AL1 (NCT01659658) is an international, randomized, controlled, open-label, multicenter, Phase 3 study, designed to determine whether NINLAROTM (ixazomib) in combination with dexamethasone improves hematologic response, two-year vital organ (heart or kidney) deterioration and mortality rate versus a physician's choice of a chemotherapy regimen in participants diagnosed with relapsed or refractory systemic light chain (AL) amyloidosis. 168 patients were enrolled and randomly selected to receive either NINLARO plus dexamethasone, or physicians choice of the following: dexamethasone plus melphalan; dexamethasone plus cyclophosphamide; dexamethasone plus thalidomide; dexamethasone plus lenalidomide; or dexamethasone alone. The discontinuation of the TOURMALINE-AL1 trial was announced in June 2019. For more information, please visit https://clinicaltrials.gov/ct2/show/NCT01659658.

About AL Amyloidosis

Primary AL amyloidosis is a condition that falls under the umbrella of plasma cell dyscrasias. AL amyloidosis arises from a clonal plasma cell that produces abnormal immunoglobulin light-chain fragments. These misfolded light-chains form insoluble fibrils that aggregate as amyloid deposits in organs and tissues throughout the body, ultimately leading to organ dysfunction and death. The most common organs affected are the kidneys, heart, liver, and autonomic or peripheral nerves.

There are currently no treatments approved for the treatment of AL amyloidosis.

About NINLAROTM (ixazomib) capsules

NINLARO (ixazomib) is an oral proteasome inhibitor which is being studied across the continuum of multiple myeloma treatment settings. NINLARO was first approved by the U.S. Food and Drug Administration (FDA) in November 2015 and is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. NINLARO is currently approved in more than 60 countries, including the United States, Japan and in the European Union, with more than 10 regulatory filings currently under review. It was the first oral proteasome inhibitor to enter Phase 3 clinical trials and to receive approval.

The comprehensive ixazomib clinical development program, TOURMALINE, includes several ongoing pivotal trials, which together are investigating major multiple myeloma patient populations:

In addition to the TOURMALINE program, ixazomib is being evaluated in multiple therapeutic combinations for various patient populations in investigator initiated studies globally.

NINLARO (ixazomib) capsules: Global Important Safety Information

SPECIAL WARNINGS AND PRECAUTIONSThrombocytopenia has been reported with NINLARO (28 percent vs. 14 percent in the NINLARO and placebo regimens, respectively) with platelet nadirs typically occurring between Days 14-21 of each 28-day cycle and recovery to baseline by the start of the next cycle. It did not result in an increase in hemorrhagic events or platelet transfusions. Monitor platelet counts at least monthly during treatment with NINLARO and consider more frequent monitoring during the first three cycles. Manage with dose modifications and platelet transfusions as per standard medical guidelines.

Gastrointestinal toxicities have been reported in the NINLARO and placebo regimens respectively, such as diarrhea (42 percent vs. 36 percent), constipation (34 percent vs. 25 percent), nausea (26 percent vs. 21 percent), and vomiting (22 percent vs. 11 percent), occasionally requiring use of antiemetic and anti-diarrheal medications, and supportive care.

Peripheral neuropathy was reported with NINLARO (28 percent vs. 21 percent in the NINLARO and placebo regimens, respectively). The most commonly reported reaction was peripheral sensory neuropathy (19 percent and 14 percent in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1 percent). Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.

Peripheral edema was reported with NINLARO (25 percent vs. 18 percent in the NINLARO and placebo regimens, respectively). Evaluate patients for underlying causes and provide supportive care, as necessary. Adjust the dose of dexamethasone per its prescribing information or the dose of NINLARO for severe symptoms.

Cutaneous reactions occurred in 19 percent of patients in the NINLARO regimen compared to 11 percent of patients in the placebo regimen. The most common type of rash reported in both regimens was maculo-papular and macular rash. Manage rash with supportive care, dose modification or discontinuation.

Hepatotoxicity, drug-induced liver injury, hepatocellular injury, hepatic steatosis, and hepatitis cholestatic have been uncommonly reported with NINLARO. Monitor hepatic enzymes regularly and adjust dose for Grade 3 or 4 symptoms.

Pregnancy- NINLARO can cause fetal harm. Advise male and female patients of reproductive potential to use contraceptive measures during treatment and for an additional 90 days after the final dose of NINLARO. Women of childbearing potential should avoid becoming pregnant while taking NINLARO due to potential hazard to the fetus. Women using hormonal contraceptives should use an additional barrier method of contraception.

Lactation- It is not known whether NINLARO or its metabolites are excreted in human milk. There could be potential adverse events in nursing infants and therefore breastfeeding should be discontinued.

SPECIAL PATIENT POPULATIONSHepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.

Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease (ESRD) requiring dialysis. NINLARO is not dialyzable and, therefore, can be administered without regard to the timing of dialysis.

DRUG INTERACTIONSCo-administration of strong CYP3A inducers with NINLARO is not recommended.

ADVERSE REACTIONSThe most frequently reported adverse reactions ( 20 percent) in the NINLARO regimen, and greater than in the placebo regimen, were diarrhea (42 percent vs. 36 percent), constipation (34 percent vs. 25 percent), thrombocytopenia (28 percent vs. 14 percent), peripheral neuropathy (28 percent vs. 21 percent), nausea (26 percent vs. 21 percent), peripheral edema (25 percent vs. 18 percent), vomiting (22 percent vs. 11 percent), and back pain (21 percent vs. 16 percent). Serious adverse reactions reported in 2 percent of patients included thrombocytopenia (2 percent) and diarrhea (2 percent). For each adverse reaction, one or more of the three drugs was discontinued in 1percent of patients in the NINLARO regimen.

For European Union Summary of Product Characteristics: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-Product_Information/human/003844/WC500217620.pdf For US Prescribing Information: https://www.ninlarohcp.com/pdf/prescribing-information.pdf For Canada Product Monograph: http://www.takedacanada.com/ninlaropm

About Takeda Pharmaceutical CompanyTakeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Diseases, Neuroscience and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries.

For more information, visit https://www.takeda.com

Important Notice

For the purposes of this notice, press release means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (Takeda) regarding this release. This press release (including any oral briefing and any question-and-answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. No shares or other securities are being offered to the public by means of this press release. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This press release is being given (together with any further information which may be provided to the recipient) on the condition that it is for use by the recipient for information purposes only (and not for the evaluation of any investment, acquisition, disposal or any other transaction). Any failure to comply with these restrictions may constitute a violation of applicable securities laws.

The companies in which Takeda directly and indirectly owns investments are separate entities. In this press release, Takeda is sometimes used for convenience where references are made to Takeda and its subsidiaries in general. Likewise, the words we, us and our are also used to refer to subsidiaries in general or to those who work for them. These expressions are also used where no useful purpose is served by identifying the particular company or companies.

Forward-Looking Statements

This press release and any materials distributed in connection with this press release may contain forward-looking statements, beliefs or opinions regarding Takedas future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. Without limitation, forward-looking statements often include words such as targets, plans, believes, hopes, continues, expects, aims, intends, ensures, will, may, should, would, could anticipates, estimates, projects or similar expressions or the negative thereof. Forward-looking statements in this document are based on Takedas estimates and assumptions only as of the date hereof. Such forward-looking statements do not represent any guarantee by Takeda or its management of future performance and involve known and unknown risks, uncertainties and other factors, including but not limited to: the economic circumstances surrounding Takedas global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations; the success of or failure of product development programs; decisions of regulatory authorities and the timing thereof; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the timing and impact of post-merger integration efforts with acquired companies; and the ability to divest assets that are not core to Takedas operations and the timing of any such divestment(s), any of which may cause Takedas actual results, performance, achievements or financial position to be materially different from any future results, performance, achievements or financial position expressed or implied by such forward-looking statements. For more information on these and other factors which may affect Takedas results, performance, achievements, or financial position, see Item 3. Key InformationD. Risk Factors in Takedas most recent Annual Report on Form 20-F and Takedas other reports filed with the U.S. Securities and Exchange Commission, available on Takedas website at: https://www.takeda.com/investors/reports/sec-filings/ or at http://www.sec.gov. Future results, performance, achievements or financial position of Takeda could differ materially from those expressed in or implied by the forward-looking statements. Persons receiving this press release should not rely unduly on any forward-looking statements. Takeda undertakes no obligation to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results of Takeda in this press release may not be indicative of, and are not an estimate, forecast or projection of Takedas future results.

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Takeda to Present Results from the Phase 3 TOURMALINE-AL1 Trial of NINLARO in Patients with Amyloidosis - Business Wire

Cancer gene therapy backed by Blackstone gets trial win – BioPharma Dive

A gene therapy for bladder cancer that recently received $400 million in support from the private equity company Blackstone Group helped more than half of treated patients with resistant disease achieve remission.

The therapy, called nadofaragene firadenovec, was discovered by a Finnish-based research institute and first entered clinical study in 2012. The data revealed today at the Society of Urologic Oncology meeting came from a Phase 3 trial that is part of the agent's Biologics License Application now before the FDA.

Licensed by its original owner, FKD Therapies Oy, to Switzerland-based Ferring Pharmaceuticals, nadofaragene firadenovec is now in the hands of the U.S. subsidiary FerGene. That company was created with the Blackstone investment and an additonal $170 million from Ferring. FerGene will commercialize the gene therapy in the U.S., with Ferring holding rights elsewhere.

Nadofaragene firadenovec is an an adenovirus-based gene therapy encoding production of the immunity-stimulating protein interferon alfa-2b. Viral vectors containing the gene are administered by catheter once every three months into the bladder, where they are absorbed into cells in the organ's walls and begin stimulating interferon.

Delivery through a catheter, called intravesical administration, limits systemic exposure to both the viral vectors and to inteferon, said Neal Shore, medical director for the Carolina Urologic Research Center and an investigator in the trial.The side-effects of interferon include flu-like symptoms in patients who inject it for other conditions like multiple sclerosis.

The clinical trial enrolled 157 patients with bladder cancer that has not spread to muscle walls and has stopped responding to treatment with Bacillus Calmette-Gurin vaccine.

Alternative treatments for these patients include chemotherapy or a procedure called "complete cystectomy." This surgery entails complete removal of the bladder, which in men means removal of the prostate and seminal vesicles and in women the uterus, ovaries, fallopian tube and part of the vagina.

"Radical cystectomy is one of the most invasive surgeries we do not just in urology but in all of surgery," Shore said, requiring a lengthy hospital stay and having a high rate of post-procedural complications.

Out of a group of 103 patients with superficial tumors in the bladder wall, just over half were in complete remission at three months, 41% at six months, and 24% at one year. In a group of 48 patients whose cancer had spread to the connective tissue outside the bladder, 73% had no recurrence of serious disease at three months, which fell to 44% at 12 months.

In this type of bladder cancer, the FDA has said a single-arm trial, without a placebo control, using complete remission is sufficient to be considered for approval, and the study does not need to pre-specify a rate that would define success. "The natural history of [disease]is well understood, and the complete response rate is negligible in the absence of therapy," the agency said in guidelines published in February 2018.

One chemotherapy agent, called Valstar (valrubicin), is approved for this patient group. It won FDA approval on a complete response rate of 18%.

In seeking FDA approval, nadofaragene firadenovec is in a race with Merck & Co.'s Keytruda (pembrolizumab) to achieve approval first. That immuno-oncology agent tested Keytruda in a similar population in the Keynote-057 trial, in which it achieved a 39% complete response rate.

Keytruda will be the subject of a meeting of the FDA's Oncologic Drugs Advisory Committee on Dec. 17.

Aside from the remission rates,Shore said nadofaragene firadenovec would differentiate itself from Keytruda in practice because its intravesical delivery means it could be administered by community-based urologists at outpatient clinics.

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Cancer gene therapy backed by Blackstone gets trial win - BioPharma Dive

Counterculture 73: Summer Jam, Timothy Leary and the Sexual Revolution – Rolling Stone

In the new book 1973: Rock at the Crossroads, writer Andrew Grant Jackson gives a comprehensive account of the year of 1973 and its legendary music and momentous social change. He breaks down the iconic year chronologically, from the release of Led Zeppelins Houses of the Holy in March to The Exorcist hitting theaters in December. Read a chapter below, titled Counterculture 73, in which Jackson breaks down the pivotal counterculture moments of the summer.

The Summer Jam at Watkins Glen, New York, on July 28 makes the Guinness Book of World Records for largest concert with the Grateful Dead, Allman Brothers, and the Band. Esalen fuels the Human Potential Movement. Time puts Carlos Castaneda on the cover while the authorities put Timothy Leary in a cell next to Charles Manson. George Harrison and Steve Jobs pay heed to Ram Dass. The Sexual Revolution reaches a peak with New York Yankee wife swappers, key parties, streakers, and Deep Throat court cases. The New Hollywood filmmakers bring visionary realism to the big screen.

Woodstock, Isle of Wight, and Watkins Glen those were the big three for us, said the Bands Rick Danko. They played Watkins Glens Grand Prix Racecourse after two long sets by the Grateful Dead, interrupted by a thunderstorm. The Allmans played last, as they were the biggest draw, a few days away from releasing Brothers and Sisters, which sold 760,000 in less than a month. All three jammed for the encore on Not Fade Away, Mountain Jam, and Johnny B. Goode.

The Dead had inspired the Allmans to incorporate jazz into their extended blues rock improvisations, while the Band had inspired the Dead to explore their Americana roots on Workingmans Dead and American Beauty. The Dead was moving away from Americana now toward a smooth jazz sound with the arrival of keyboardist Keith Gordchaux. The cover of their new album, Wake of the Flood, featured a benign reaper, reflecting the loss of their original organist, the blues-oriented Pigpen (Ron McKernan), who died on March 8 from gastrointestinal hemorrhage due to alcohol abuse. It also reflected how the band was beginning to reap the rewards of their endless trip. They were now able to fill stadiums, and theyd done it all their way: through touring, regardless of record sales, establishing the economic model for jam bands like the Dave Matthews Band and Phish.

For a time, Watkins Glen was listed in the Guinness Book of World Records as largest audience for a pop festival, with a crowd estimated at 600,000. It beat Woodstock by approximately 200,000 but carried none of the cultural resonance. No movie was released, and only a couple songs made it onto record: Come and Go Blues on the Allmans Wipe the Windows, Check the Oil, Dollar Gas and an eighteen-minute sound check on the Deads So Many Roads box set.

It had already been done: the hordes getting in for free, dancing in the nude, breastfeeding. There was no longer any war they needed to bond together against. But its very meaninglessness revealed the extent to which the counterculture had been absorbed into the culture. Documentarian Michael Moore wrote in his memoir that by 1971 the longhairs outnumbered the jocks in his high school, though hippies still had to travel in packs or get jumped. Even the hair of conservative kids jutted out from behind their neck in yearbook photos. Richard Carpenter visited Nixon in the White House with hair over his ears. Merle If you dont love it, leave it Haggards thick muttonchops puffed down to his neck.

The original hippie mecca Haight-Ashbury had fallen on hard times. The New York Times reported that a third of its shops were boarded up. But the Dead transformed the neighborhoods spirit into a movable holiday through its tours. Believers could check in once every few years, or follow them around in a raggedy caravan of Volkswagen buses for months at a time. As Robert Christgau noted, Regulars greeted other regulars, remembered from previous boogies, and compared this event with a downer in Boston or a fabulous night in Arizona. Dead Heads sold items in the parking lots to finance their treks: jewelry, fanzines, burritos, dope, tie-dye shirts (a tradition carried over from Ken Keseys Merry Pranksters, who made tie-dye shirts on their own 1964 cross-country road trip).

One thing they didnt sell but traded was tapes of Dead shows. The tradition started when fans hungered to replay the music the Dead performed in concert but realized they couldnt find it in their studio albums. The band seldom played a song the same way twice and made a point of playing at least one different song a show. Fans started taping shows off radio broadcasts or sneaking recording equipment into gigs. The Dead had been close to the Haight-Ashbury activists the Diggers, who promoted the radical policy that everything should be for free, so they did not complain when mic stands rose above the crowds, reaching for better sound. One of the central figures in the Dead tape exchange was Dick Latvala; decades later, his favorite shows were officially released through the Dead under the name Dicks Picks. The first concert he chose to release was their December 19, 1973, concert in Tampa, Florida, because it included Nobodys Fault but Mine, a track prized for its rarity.

The Dead officially released one live album in 1973, and it introduced two of their most enduring logos. Bears Choice was named for their soundman Owsley Bear Stanley, originally one of the biggest acid manufacturers, and featured marching bears on the back cover. The front showed a skull with a lightning bolt in the brain cavity, representing the effect of his lysergic product. Stanley originally designed the image to print on stickers that he slapped on band equipment, to identify it as theirs when they played gigs with other bands.

The Dead community propagated another hallucinogen-related tradition that spread far beyond their own scene. Bassist Phil Lesh had a personal manager who was brother to a San Rafael high school student who ran with a clique that called themselves the Waldos, after the wall they sat on between classes. One day in 71 the Waldos gave each other the code 420 Louis meaning meet at the schools statue of Louis Pasteur at 4:20 p.m. in order to get high and search for a marijuana patch they heard had been planted in the area. 420 became the teens go-to term for pot, so parents or teachers wouldnt know what they were referring to, and spread into the Deads orbit. Years later, the Oxford English Dictionary credited the Waldos with originating the term, after studying a 1974 issue of their school paper in which they used it.

The main Dead Head tradition, of course, was going to a show, ingesting hallucinogens to block the serotonin receptors, and somehow hitting that chord of realization of the unity of God in you all, as comparative religion scholar Joseph Campbell put it in his symposium with Dead drummer Mickey Hart called Ritual and Rapture: From Dionysus to the Grateful Dead.10 As Tom Wolfe noted in The Electric Kool-Aid Acid Test, hallucinogens created a chemical reaction in the brain analogous to religious awe.

Or a plunge into the abyss, depending on how your trip was going. But Wake of the Flood included Eyes of the World, which became the new happy anthem to bring audience members back from staring at their shoes on the edge of freaking out. Wake now, discover that you are the song the morning brings, and look around at the concert and realize holy shit how beautiful everything is and were all made of atoms and were all just one field of energy endlessly permutating on the surface and everything is one, and WHOOOOOOOO!

Dr. Timothy Leary displays a big smile as hes escorted by U.S. Narcotics Bureau agents on his arrival at Los Angeles airport. The former Harvard professor escaped in September, 1970 from prison in San Luis Obispo County, Calif., where he was serving a 10-year sentence on a drug conviction. Photo credit: AP/Shutterstock

The fates of the original Dynamic Duo of Acid, Timothy Leary and Richard Alpert, illustrated with jarring clarity just how well or how bad the great mental/spiritual experiment could go. They had been professors at Harvard investigating the benefits of psychedelics until the university fired them because the program had grown too controversial, and because Alpert gave a hallucinogen to an undergraduate. (He was an attractive kid, said Alpert.) With the help of theorist Marshall McLuhan Leary concocted the slogan Turn on, tune in, drop out and proclaimed it at the San Francisco Human Be-In, which might have been fine, but he followed the line with I mean drop out of high school, drop out of college, drop out of graduate school. They gave him twenty years in prison for two roaches of marijuana. The acid cartel the Brotherhood of Eternal Love paid the Weather Underground militants to help him escape from prison. But officials nabbed him again in Kabul International Airport on January 17. As the authorities dragged him past the news cameras, it was terrifying to look at him. Hed always been handsome, known for his smile. McLuhan advised him always to smile to the press, so he did so now, to show that they couldnt crush him. But he looked crazy, like the Joker or Dracula, or a scary beaten dog. They took him to Folsom two days before Nixons second inauguration and stashed him in the cell next to Charles Manson.

Alpert embodied a preferable trajectory: Western academic psychiatry to psychedelics to Eastern mysticism. He traveled to India and met fellow seeker Kermit Riggs, who had renamed himself Bhagavan Dass. When my mind would go off into Jewish neuroticism, Bhagavan Dass would say, Come back here and be here now. Alpert renamed himself Ram Dass (servant of God) and published Be Here Now in 1971. He hit the lecture circuit in a white robe, sponsored retreats, and sold tapes. Be Here Now sold two million copies and was followed by Doing Your Own Being in 1973.

George Harrison included a song called Be Here Now on Living in the Material World. On the title track Harrison proselytized for the Hare Krishnas. The Krishna teacher Srila Prabhupada had arrived in the States in 1965, the year the US ended its policy of severely restricting non-European immigrants. Prabhupada started chanting in Tompkins Square Park with Allen Ginsberg. Not long after, Harrison and Lennon heard his first album, Krishna Consciousness.

After the passage of the Immigration and Nationality Act of 1965, many swamis and yogis arrived in the States, often teaching yoga, an Indian tradition since 1500 BC. By 1975, Time estimated that 600,000 Americans including Mike Love, Shirley MacLaine, and Joe Namath practiced it. On January 13, Cat Stevenss song about meditation, Sitting, peaked at No. 16.

March saw the release of Lost Horizon, about survivors of a plane crash in the Himalayas who stumble upon the utopia of Shangri-La. The author of the original novel, James Hilton, probably named his city after Shambhala, a Sanskrit word that means peace/serenity/joy. Ancient Tibetan Buddhist scripture referred to it as a fabled city in the Himalayas. The movie didnt perform well, despite a Burt Bacharach/Hal David soundtrack, clanging the death knell for the big Hollywood musical. The songwriters stopped working together. Not very Zen. But perhaps it inspired LA-based songwriter Daniel Moores euphoric Shambala, which Three Dog Night took to No. 3 in July. Its yodeling groove was so uplifting that Moore rewrote it as the secular My Maria and got another hit out of it when it was released a month later by progressive country artist B. W. Stevenson.

Many were still on the road to Shambala in real life, on the hippie trail to India. Tony and Maureen Wheeler traveled from London through the Middle East to India to Australia, arriving down under with $0.27 to their name. They shared what they learned in Across Asia on the Cheap, the first of their Lonely Planet Travel Guide books.

John Lennon celebrated all the journeys hed been on in space and in time, from meditation to primal scream therapy in Mind Games, recorded that summer. He was inspired by a book called Mind Games: The Guide to Inner Space by Robert Masters and Jean Houston, consisting primarily of exercises to increase visionary thinking and intuition (hence another song on the Mind Games album, Intuition).

Houston was a figure in the Human Potential Movement, which had its own Shambala in Esalen, off the winding Pacific Coast Highway in Big Sur. Nude sulphur baths built into the mountains looked out over the ocean as the surf crashed and shimmered in the moonlight. Founders Michael Murphy and Dick Price brought in speakers and held workshops covering the latest advances in Western psychiatry along with Eastern philosophy and psychedelics. That was the Great Synthesis: Western psychiatry + Eastern mysticism + psychotropic shamanism. Buddhist scholar Alan Watts gave the first lecture at Esalen. Aldous Huxley provided the movement with its name when he gave talks on Human Potential before his death in 1963. Leary and Alpert spoke there alongside others promoting self-actualization techniques ranging from Gestalt to Rolfing to biofeedback.

The Esalen encounter group was recreated in Bob & Carol & Ted & Alice (1969) and in the 2015 series finale of Mad Men. It rose out of the Sensitivity Training Group pioneered by social psychologist Kurt Lewin. In 1946, the Connecticut State Interracial Commission asked him to create a program that could help fight racial and religious discrimination.13 He gathered forty-one people together, half of them Jewish or black, so psychologists could analyze their interactions and give them feedback in a group setting, helping them become more sensitive to the other attendees feelings.

Now Marvin Gaye sang, Were all sensitive people, in Lets Get It On. Its all right to cry, Rosie Grier sang on the Free to Be You and Me album, in development for a TV special. In 1970, approximately one million Americans went to therapy. In five years the number was six times as great. Celebrities like Hugh Hefner, John Denver, and Peter Fonda spoke of their sadness at their parents inability to demonstrate affection. Im OK Youre OK and How to Be Your Own Best Friend were on the bestseller list throughout the year.

The No. 1 bestseller from January 1 through March 18 was Jonathan Livingston Seagull, a fable about an outcast yearning to fly on a higher plane. Many readers wondered what religion author Richard Bach himself belonged to (if any). His son said, Dad regards flying as his religion, and hes very serious about that. Bach had been a pilot in the US Air Force Reserve in France, a member of the New Jersey Air National Guard, then a technical writer for Douglas Aircraft and contributor to Flying magazine.

In 1959, Bach heard a voice behind him say Jonathan Livingston Seagull. John Livingston had been a race pilot. Bach asked the voice what it meant, and the story poured out of him onto the page, unfolding like a movie in his mind. Eight years later he published part of it in Private Pilot magazine.

Hed been a Christian Scientist, then decided that organizations can ruin anything and started searching through occult bookstores. It took nerve, just to go in one of those places, he told Time in their cover story on him. Time reported that his interest led him to a medium named Jane Roberts, who claimed to channel a spiritual being with an Indian accent named Seth.

The movie version of Seagull was poorly received by critics, like Lost Horizon, but the Neil Diamond soundtrack went to No. 2 and won the Grammy for Best Original Score, along with a Golden Globe.

Another bestselling writer made the cover of Time in March. Carlos Castaneda was an ethnobotany student whose anthropology professor instructed him to interview a shaman about psychotropic plants. Castaneda supposedly found one named Don Juan on the Arizona/Mexico border. His thesis was eventually published as The Teachings of Don Juan: A Yaqui Way of Knowledge (1968), which made Castaneda a millionaire and inspired three sequels. Castaneda had more surreal visions than Aldous Huxley or Ram Dass; on Don Juans medicine he witnessed giant gnats and talking coyotes and turned into a bird. But his message of enlightenment was the same: stop the world to see, a.k.a. be here now. The Eagles name was partially inspired by his books; Marvin Gaye dug them. But Time and other journalists couldnt find a real Don Juan. The tribe Castaneda said Don Juan belonged to didnt use the same kind of peyote Castaneda said he used. Critics noted that Don Juans personality seemed to change from book to book. After the Time piece, Castaneda claimed Don Juan died in 1973, then retreated from view for the next twenty years, after which he returned to teach seminars about Mexican shamanism.

A third author who combined ancient mysticism with psychedelics was about to join Castaneda on the chart, though he was painfully up-front about his tortured past. Robert Pirsigs Zen and the Art of Motorcycle Maintenance recounted his attempt to reconnect with his son on a motorcycle trip following a nervous breakdown and electroshock therapy, precipitated by his quixotic attempt to create his own system of metaphysics. After serving in Korea, Pirsig had become intrigued by Buddhism and studied in India, then did peyote on a Cheyenne reservation. The next year he was institutionalized on Christmas. When he got out, he grew violent toward his wife and received shock therapy. After recovering, he worked on Zen for four years, the last few months working in a camper in Minnesota. He sold the book in January 1973, and it eventually sold five million copies.

Alongside those authors, the Occult and Astrology bookshelf in bookstores now offered up much of the entire Western mystery tradition, a catalog that once had to be studied in secret, lest the reader incur the wrath of the Church. Samuel Weisers Inc., Specialist in the Occult, Orientalia, and Metaphysics, was one of New Yorks oldest occult bookstores. Weiser started selling Aleister Crowleys papers in the 50s but was not able to expand his operation until the 60s, when he began selling to the new occult bookstores bourgeoning in California. A watershed in occult publishing occurred in 1973 when two competing versions of a book called Pyramid Power sold a million, abetted by chain bookstores in malls rapidly spreading across the country, Waldenbooks and its competitor B. Dalton. Eventually the Trade Association of Independent Bookstores gave the Occult category a new name, New Age, replacing a horror-movie term with one used by theosophists and the Fifth Dimension in their hit from Hair, Aquarius/Let the Sunshine In.

A few rows over in the bookstore, the sexual revolution had arrived with an explicitness unimaginable to earlier authors crushed by obscenity court cases. Alex Comforts More Joy of Sex, his sequel to last years smash The Joy of Sex: A Gourmet Guide to Lovemaking, featured positions illustrated by Chris Foss and Charles Raymond. The New York Times later ranked the author on par with Dr. Spock in terms of impact, while Planned Parenthoods executive Joan Malin said, The groundbreaking publication of this book took us from an era of silence and shame about sexuality to one of greater openness and discussion. It started out as a textbook for medical students by Comfort, who admitted he was hardly an expert on the topic at the outset. Thats the way to find about anything, to write a book about it. He advised that female armpits should on no account be shaved and deodorant should be banned absolutely, and he cautioned, Never fool around sexually with vacuum cleaners.

Next to it on the shelf was George and Nena ONeills Open Marriage: A New Life Style for Couples, which spent over forty weeks on the bestseller chart. We are not recommending outside sex, but we are not saying that it should be avoided, either. The choice is entirely up to you.

By the early 70s there were over 650 swinging publications. Typical was the scene at the Swing Bar in LAs Studio City, with a marquee that read LUV THY NEIGHBOR. The bartender determined whether you got the invite to the mansion party, where men had to arrive with a date. The Swings owner, Greg McClure, told Newsweek, In my first marriage I cheated and never felt comfortable about it. Swinging is way ahead of the infidelity scene. I swing so I wont break up my marriage.

The Club 101 mansion boasted waterbeds and a chamber of mirrors. In a Detroit swingers gathering, guests mingled as at any cocktail party until the appointed time, when the host announced that anything went as long as all partners consented. Some couples waited in line for private rooms; others made do with the rows of cots in the basement. The key party was recreated in the 1997 film The Ice Storm. Attendees threw their car keys in a bowl, then plucked them out at random to see who would go with whom. The National Key Club (NKC) staged hotel events.

Key parties reputedly began on air force military bases during World War II, according to historian Terry Gould, as a kind of tribal bonding ritual, with a tacit understanding that the two-thirds of husbands who survived [the war] would look after the widows. Gould maintained that military bases across the country had swing clubs, which spread into the suburbs in the early 50s, along with swinger magazines.

On March 4, 1973, wife swapping reared its head in the great American pastime when New York Yankees pitchers Mike Kekich and Fritz Peterson figured theyd better get ahead of the story and held separate press conferences to announce they had switched wives.

Peterson later explained, During (a) party, we all had a couple of beers and were having a great time. When we were deciding to leave, we had driven two different cars and happened to park behind each other out in the street. I said to my wife, Marilyn, Why dont you ride with Mike to the diner in Fort Lee, N.J., and Ill take Susanne with me and well meet there and then well go home from there. We did that and we had so much fun together, Susanne and I and Mike and Marilyn, that we decided, Hey, this is fun, lets do it again.

Peterson and Susanne Kekich remained together over the ensuing decades, but Marilyn Peterson soon wished she was back with her former husband and split with Kekich. Marilyns mother lamented to the press, Fritz is not the same person he used to be. We cant understand any of his ideas or his problems anymore. The crowd booed Peterson, both players games suffered, and both were traded within the year. Dr. Joyce Brothers opined, Its very rare that a four-way swap ever works.

Still, curious couples ventured to the Shambala of swinging, Sandstone Retreat, in the mountains of Santa Monica. The fifteen acres in Topanga Canyon looked out at Malibu and the Pacific Ocean. If you were over eighteen, the nude woman at the front desk interviewed you to decide whether you could come in. Sometimes people had sex in the reception room, but more typically downstairs by the fireplace on pillows and mats. Gay Talese wrote that in 1973, often the nude biologist Dr. Alex Comfort, brandishing a cigar, traipsed through the room between the prone bodies with the professional air of a lepidopterist strolling through the fields with a butterfly net. With the least encouragement after he had deposited the cigar in a safe place he would join a friendly clutch of bodies, and contribute to the merriment. Its five hundred members included Bobby Darin and Daniel Ellsberg. Sammy Davis Jr. and Peter Lawford visited.

Alas, the owners had to sell the resort in 73, though it stayed open for another three years. Barbara Peterson, founder with husband John, observed, Sandstone had been a great source of fulfillment, learning, and pleasure. It had been everything, in fact, except financially viable.

Even in the mainstream, Puritan/Victorian conventions were rapidly melting away, such as the need to be a virgin until marriage, the need to be in love to have sex, the need to marry early, the traditions of female subservience. More unmarried couples lived together, as did the protagonists in McCartneys C Moon, though they never told her daddy. There did not seem to be any permanent STDs. If you got the clap, you got a shot. We had a soft spot in our hearts for the free clinics, said Jackson Browne. Steven Tyler wrote about lighting his pubic hair on fire to get the crabs to run out, but that seemed as bad as it got.

In March, a reporter covered a nude run at the University of Maryland with 553 participants and popularized the name for the new trend when he cried, They are streaking past me right now. Its an incredible sight! Time declared streaking a Los Angeles fad, reporting on a female streaker in tennis shoes who led the police on a chase across the ice during a hockey game at the Inglewood Forum.

The braless look graced Carly Simons No Secrets cover and Linda Ronstadts publicity photos, though Ronstadt lamented, In all of the world, outside of California, if you dont wear a bra it supposedly means you want to fuck everybody. When a man at the airport asked her, Hey, chick, you wanna get laid? I just hauled off and slugged him right in the mouth.

Advertisements even hawked bras with nipples built into them. Imagine having that sensual cold weather look all the time. Its so sexy, itll give your shape a whole new eye-opening dimension.

Responding to competition from Penthouse, Playboy showed a few wisps of pubic hair in 1971. Marilyn Cole (later on Roxy Musics Stranded cover) went full frontal a year later, but with a shadow across her. It wasnt until March 1973 that Hugh Hefner presented the first unobstructed view, with Playmate Bonnie Large.

That was the same month Judge Joel Tyler decreed Deep Throat obscene and fined Manhattans New Mature World Theatre $100,000 for screening it. His decision came down after a ten-day trial during which experts argued over whether oral sex was within the bounds of normal behavior. The prosecutor against Deep Throat, William Purcell, argued, A woman seeing this film may think that it is perfectly healthy, perfectly moral to have a clitoral orgasm. She is wrong. She is wrong. And this film will strengthen her in her ignorance. Defense experts countered that educating couples in sexual practices helped prevent divorce.

For a brief moment, before stories of Linda Lovelaces abuse leaked out, seeing porn became an idealistic cause clbre. It was exercising the First Amendment, embracing personal liberation against outmoded Victorian repression, asserting that nudity and sex were beautiful, not sinful. Deep Throats attorney, Herbert Kassner, argued, It indicates that women have the right to a sex life.

The New York Timess Vincent Canby opined, You can argue that Linda in her way is a kind of liberated woman, using men as sex objects the way men in most porno films are supposed to use women.

Even Bob Hope joked about it now. I went to see Deep Throat because Im fond of animal pictures. I thought it was about giraffes. On Maude, Bea Arthur fought to stage a burlesque show for a library benefit.

The groundbreaking sex scenes between Last Tango stars Brando and Schneider emboldened director Nicolas Roeg to attempt to top them in Dont Look Now with Julie Christie and Donald Sutherland. The latter film was shot in Italy just as police were seizing all of the countries copies of Last Tango on grounds on obscenity.

Marquee of The New Mature World Theatre which is showing the porno-film, Deep Throat. on West 49th Street in New York. Photo credit: Bettman Archive/Getty Images

Filmmakers with counterculture sensibilities had, for the moment, the run of Hollywood. After a string of box office bombs, the studios realized they were out of touch with modern sensibilities and (briefly) gave young filmmakers carte blanche to experiment in films like Badlands, American Graffiti, The Long Goodbye, and Paper Moon. Though the studios sometimes drew the line: Hal Ashbys The Last Detail was delayed for six months because the film included the word fuck sixty-five times, until praise for Jack Nicholsons performance as a navy lifer forced Columbia to release it.

Many of the New Hollywood directors gathered in Nichols Beach Canyon along the Pacific Ocean (a few minutes from where Neil Young lived at Zuma), at the homes of Julia and Michael Phillips (producers of The Sting) or actresses Margot Kidder and Jessica Salt, who lived down the block, where they flew a tie-dye flag and sunbathed topless. Hitchcock disciple Brian De Palma wrote Sisters as a vehicle for them. Steven Spielberg worked on Watch the Skies, his concept based on a great wave of UFO sightings that spiked in the fall of 1973, with the Phillipses and screenwriter Paul Schrader. In the end he didnt like the script Schrader wrote. Spielberg wanted the film to be about how average Americans yearned to transcend their mundane lives of quiet desperation through contact with mystical higher beings. Schrader nevertheless interested the Phillipses and Martin Scorsese in his script for Taxi Driver. Scorsese meanwhile was inspired to use the tracking-shot technique he saw in the Pink Floyd concert film Live at Pompeii for his new film Mean Streets. His use of classic songs by artists like the Stones and Ronettes changed the way the movies used rock in soundtracks, as did George Lucass American Graffiti. Lucas was already working on the script for his follow-up, a science-fiction epic loosely based on Akira Kurosawas The Hidden Fortress by way of Flash Gordon. It was really about the Vietnam War, and that was the period where Nixon was trying to run for a [second] term, which got me to thinking historically about how do democracies get turned into dictatorships? John Milius surfed and shot off his guns. He was the token conservative in the clique, a script doctor for Dirty Harry and writer of Apocalypse Now and Big Wednesday.

Even big-budget studio soap operas that year had radical heroines. The Way We Were starred Barbra Streisand as a Communist idealist who pushes her screenwriter husband (Robert Redford) to stand up to the blacklist and write art instead of easy entertainment. He doesnt want to work that hard, however, and they split a conflict that resonated with activists who had to decide if they wanted to keep on pushing or become proto-yuppies. Arthur Laurents wrote the screenplay; hed been blacklisted for years before bouncing back with West Side Story.

Along with daring to play a sympathetic Commie, Streisand led the vogue for actors who broke the WASP mold of beauty that dominated the industry. Her own mother had warned her she wasnt pretty enough to make it, and others had advised her to change her nose and accent, but she ignored them. Movie historian Lester Friedman wrote, Streisands name and nose in their unaltered state represents a turning point in the cinematic portrayal of Jews, one that shows Jewishness as something to be proud of, to exploit, and to celebrate. Cher, too, turned her unconventional, half-Armenian beauty into an asset, making it the theme of her hits Gypsys, Tramps & Thieves, Half-Breed (which made No. 1 in October), and Dark Lady.

Dustin Hoffmans success in The Graduate also helped open the doors to performers who never would have been offered leads before: Al Pacino, Elliot Gould (Streisands husband), Richard Dreyfuss, Donald Sutherland, Gene Wilder, Robert De Niro, Jill Clayburgh. The vogue for cinematic authenticity paralleled the ascendance of offbeat musicians like Bob Dylan, Mick Jagger, Janis Joplin, and Neil Young, whose appeal was partly based on the fact that they looked and sounded real, not like airbrushed product. For Redford, The Way We Were was a cautionary tale he spent the second half of his career refuting. His character mused uneasily that everything came too easily to him . . . he was a fraud. Redford turned that into the theme of the movies he directed, which centered on the guilt of golden boys who have everything handed to them while their brothers struggle. He became the patron saint of the Sundance Film Festival, which became the haven for artistically ambitious films after the studios lost their brief interest in funding experimental directors.

The bte noir of the counterculture was, of course, the military-industrial complex. But in a mind-boggling twist, the antagonists merged toward a great synthesis that determined the next phase of human evolution.

Significant milestones in computer technology that year included the first TV typewriter and the first computer monitor. Motorolas Martin Cooper made the first call with his invention, the handheld cell phone, inspired by Dick Tracys wrist radio. Xerox Palo Alto Research Center employees created the Ethernet when they linked all the computers and printers in their network with a coaxial cable. The forty-three high-powered US computers linked in the Advanced Research Projects Agency (ARPA) network made their first connection to computers outside the US in England and Norway.

Author Dean Koontz riffed off the Rosemarys Baby premise with his bestselling novel Demon Seed, about a computer that takes a woman hostage and impregnates her, creating a cyborg. But the Dead Heads who worked in Silicon Valley found benign uses for the technology, employing proto-messaging boards to arrange rides to concerts and compile lyrics to Grateful Dead songs, a resource the band itself eventually used. Merry Prankster Stewart Brand, creator of the commune-oriented Whole Earth Catalogue, wrote in Rolling Stone, Ready or not, computers are coming to the people. Thats good news, maybe the best since psychedelics. Half or more of computer science is heads. The rest of the counterculture is laid low and back these days, showing none of this kind of zeal.

In the article, Brand asked Alan Kay of the Xerox Research Center to describe the standard Computer Bum. About as straight as youd expect hotrodders to look. Its that kind of fanaticism. A true hacker is not a group person. Theyre kids who tended to be brilliant but not very interested in conventional goals. And computing is just a fabulous place for that, because its a place where you dont have to be a Ph.D. or anything else. Its a place where you can still be an artisan. People are willing to pay you if youre any good at all, and you have plenty of time for screwing around.

The man who most famously epitomized the archetype walked around barefoot, dropped out of college, read Be Here Now, ate at the Hare Krishna Temple, saved up to go to India, lived at his friends commune, and pruned the communes apple orchard, which inspired the name of the computer he eventually created with compadre Steve Wozniak. I came of age at a magical time. Our consciousness was raised by Zen, and also by LSD, Steve Jobs said. LSD shows you that theres another side to the coin, and you cant remember it when it wears off, but you know it. It reinforced my sense of what was importantcreating great things instead of making money, putting things back into the stream of history and of human consciousness as much as I could.

U2s Bono said of the techies, The people who invented the twenty-first century were pot-smoking, sandal-wearing hippies from the West Coast like Steve, because they saw differently. The hierarchical systems of the East Coast, England, Germany, and Japan did not encourage this different thinking. The sixties produced an anarchic mind-set that is great for imagining a world not yet in existence.

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Counterculture 73: Summer Jam, Timothy Leary and the Sexual Revolution - Rolling Stone

Precision Cancer Therapies Market Size, Status and Forecast 2025 Trends, Size, Drivers, Strategies, Products and – The Market Stats News

Precision Cancer Therapies Market research now available at Brand Essence Research encompasses an exhaustive Study of this business space with regards to pivotal industry drivers, market share analysis, and the latest trends characterizing the Precision Cancer Therapies industry landscape. This report also covers details of market size, growth spectrum, and the competitive scenario of Precision Cancer Therapies market in the forecast timeline.

The Precision Cancer Therapies Market Report provides key strategies followed by leading Precision Cancer Therapies industry manufactures and Sections of Market like- product specifications, volume, production value, Feasibility Analysis, Classification based on types and end user application areas with geographic growth and upcoming advancement. The Precision Cancer Therapies market report provides comprehensive outline of Invention, Industry Requirement, technology and production analysis considering major factors such as Revenue, investments and business growth.

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The well-established players in the market are:

Abbott Laboratories, Bayer HealthCare, GlaxoSmithKline, OncoGenex Pharmaceuticals, Hospira, Boehringer Ingelheim, AstraZeneca, Aveo Pharmaceuticals

This report for Precision Cancer Therapies Market discovers diverse topics such as regional market scope, product market various applications, market size according to specific product, sales and revenue by region, manufacturing cost analysis, Industrial Chain, Market Effect Factors Analysis, market size forecast, and more.

Drivers & Hindrances of the Precision Cancer Therapies market: How does the report explicate on the same

The report unveils the driving parameters affecting the commercialization chart of this industry.

The Precision Cancer Therapies market research report further illustrates the various challenges that this market is prone to as well as its impact on the market trends.

An important aspect that the report sets focus on is the market concentration ratio for the predicted timeframe.

Important Points Mentioned In the Precision Cancer Therapies Market

Manufacturing Analysis:The report comprises descriptive information after analyzing multiple segments of Precision Cancer Therapies market, which include product type and applications, among others. Precision Cancer Therapies market report includes a separate chapter emphasizing thorough analysis of the manufacturing process authenticated via primary information gathered from key officials of reputed industries and several industry analysts.

Sales and Revenue Estimation:By implementing several top-down and bottom-up approaches on the historical sales & revenue data and the current market status, the researchers have forecasted the market growth and size in key regions. Moreover, the report includes a comprehensive study on classified and prominent types as well as end-use industry. The report even provides significant information related to regulatory policies and macroeconomic factors that determine Precision Cancer Therapies industry evolution and predictive analysis.

Demand & Supply Assessment:Precision Cancer Therapies report also offers important information on product & service distribution, manufacturing, Consumption, and Export & Import (EXIM) ** if applicable.

Competitiveness:Precision Cancer Therapies report provides key information based on the product portfolio, company profile, product & service cost, potential, and sales & revenue generated by the global and regional leading companies.

Market segment by Type, the product can be split into

Hormone Therapy, Immunotherapies, Targeted Therapy, Monoclonal Antibody Therapy, Gene Therapy

Market segment by Application, split into

Hospitals, Diagnostic Centers, Oncology Clinics, Research Institutes

Market segment by Regions/Countries, this report covers

North America (United States, Canada and Mexico)

Europe (Germany, UK, France, Italy, Russia and Turkey etc.)

Asia-Pacific (China, Japan, Korea, India, Australia, Indonesia, Thailand, Philippines, Malaysia and Vietnam)

South America (Brazil etc.)

Middle East and Africa (Egypt and GCC Countries)

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Key highlights and essential features of the report:

1) Which major players are presently listed in the report?Here are the companies that are presently listed in the report: Abbott Laboratories, Bayer HealthCare, GlaxoSmithKline, OncoGenex Pharmaceuticals, Hospira, Boehringer Ingelheim, AstraZeneca, Aveo Pharmaceuticals

**List of the firms stated above might differ in the final report dependent on a merger, name change, and other factors.

2) Can you list or add new firms as per our requirement?Yes,we can list or add new firm as per the requirement by client in the report. The final confirmation regarding the same must be provided by the research team subject to difficulty of survey.

**Availability of data will be confirmed after research in case of a privately held firm. Maximum 3 companies can be included at no additional charge.

3) Which all regional categorization are covered? Is it possible to add any specific country?Presently, our research report offers special focus and attention on the following areas:Europe, United States, Japan, China, India, Southeast Asia, and Central & South America

**Maximum one country of specific interest can be added at no extra charge. Charges will be applied for the addition of extra countries or regions.

4) Can the addition of extra Market breakdown or segmentation is possible?Yes, the addition of extra Market breakdown or segmentation is possibly dependent on the difficulty of survey and availability of data. On the other hand, detailed sharing of the requirements with our research team is a must before providing final confirmation to the client.

More Details on this Report: https://brandessenceresearch.biz/Medical-Devices-and-Consumables/Global-Precision-Cancer-Therapies-Industry-Market-Research-2019/Summary

There are 15 Chapters to display the Global Precision Cancer Therapies market

Chapter 1, Definition, Specifications and Classification of Precision Cancer Therapies , Applications of Precision Cancer Therapies , Market Segment by Regions;

Chapter 2, Manufacturing Cost Structure, Raw Material and Suppliers, Manufacturing Process, Industry Chain Structure;

Chapter 3, Technical Data and Manufacturing Plants Analysis of Precision Cancer Therapies , Capacity and Commercial Production Date, Manufacturing Plants Distribution, R&D Status and Technology Source, Raw Materials Sources Analysis;

Chapter 4, Overall Market Analysis, Capacity Analysis (Company Segment), Sales Analysis (Company Segment), Sales Price Analysis (Company Segment);

Chapter 5 and 6, Regional Market Analysis that includes United States, China, Europe, Japan, Korea & Taiwan, Precision Cancer Therapies Segment Market Analysis (by Type);

Chapter 7 and 8, The Precision Cancer Therapies Segment Market Analysis (by Application) Major Manufacturers Analysis of Precision Cancer Therapies ;

Chapter 9, Regional Marketing Type Analysis, International Trade Type Analysis, Supply Chain Analysis;

Chapter 10, The Consumers Analysis of Global Precision Cancer Therapies ;

Chapter 11, Precision Cancer Therapies Research Findings and Conclusion, Appendix, methodology and data source;

Chapter 12, 13 and 14, Precision Cancer Therapies sales channel, distributors, traders, dealers, Research Findings and Conclusion, appendix and data source.

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Precision Cancer Therapies Market Size, Status and Forecast 2025 Trends, Size, Drivers, Strategies, Products and - The Market Stats News