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Global Hematopoietic Stem Cell Transplant (HSCT) Market to be Driven by Increasing Prevalence of Blood Ca – Benzinga

Posted: August 5, 2022 at 2:10 am

New York, July 29, 2022 (GLOBE NEWSWIRE) -- According to the statistics by the Organ Procurement Transplantation Network (OPTN), by the United States Department of Health & Human Services, during the period January and June 2022, a total of 20663 transplants were performed in the United States, whereas 10286 donors were recovered during the same period. Further, as of 19th of July 2022, a total of 105980 candidates are in the waiting list to perform different types of transplants. On the other hand, according to the statistics by the European Society of Blood and Marrow Transplantation (EBMT), in the year 2019, the total number of HCT performed in Europe was 48512, which included 43581 first time HCT and 4931 re/additional transplants.

Research Nester examined the statistical and analytical approach that is required for the growth of Global Hematopoietic Stem Cell Transplant (HPSCT) Market' between the years 2021 and 2029. The key industrial insights provided in the report gives a better idea about the market overview to the readers regarding the existing scenario in the market. The report further includes in-depth market analysis in five major regions, i.e., North America, Latin America, Europe, Asia Pacific and Middle East & Africa, including the current and future industry trends, innovations, and challenges, along with strategies that will help industry players to attain their business targets.

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A research conducted by Worldwide Network for Blood and Marrow Transplantation (WBMT) estimated that in 2019, nearly 1.5 million HSCTs were performed globally. Over the last two decades, hematopoietic stem cell transplant (HSCT) has seen rapid expansion to become the standard of care for many patients with congenital or acquired disorders of the hematopoietic system or with chemo- radio- or, immuno- sensitive malignancies, such as lymphoma, leukemia, solid tumors, and others. Diseases, such as blood cancer (leukemia, and lymphoma), auto-immune diseases, immunodeficiency, and genetic disorders are growing in number around the world. In 2020, according to a report by the International Agency of Research on Cancer (IARC), on a global scale, out of every 100,000 individuals, 336,669 individuals were suffering from leukemia, 64,067 with Hodgkin lymphoma, and 399,610 with non-Hodgkin lymphoma. Hematopoietic stem cells have the potency to produce more blood cells, i.e., red blood cells, white blood cells, and platelets. Based on these factors, the global hematopoietic stem cells transplantation market is estimated to grow at a substantial CAGR over the forecast period, i.e., 2021-2029.

Moreover, growing adoption of stem cell transplants across the medical industry is also expected to drive the market growth. For instance, as of 2017, over 20,000 stem cell transplants, annually, were performed for hematologic malignancies in the United States, out of which, approximately 60% were allogeneic and 40% were autologous. Furthermore, the growing awareness amongst people regarding early diagnosis of rare diseases, along with the adoption of advanced treatment methods, and growing healthcare expenditure are also expected to drive the market growth.

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Geographically, the global hematopoietic stem cell transplant (HPSCT) market is segmented by region into North America, Europe, Latin America, Asia Pacific, and Middle East & Africa. Amongst the market in these regions, the market in North America held the leading market share in the year 2021 and is further projected to garner the largest market share during the forecast period. High prevalence of leukemia and lymphoma in the region is one of the major factors anticipated to drive the growth of the market. In the United States, about 60,650 cases of leukemia were reported in 2021, as per data by the American Cancer Society, out of which, 20,050 cases were of acute myeloid leukemia (AML). Further, in 2018, a total of 22,729 hematopoietic cell transplants (HCTs) were performed in the United States, as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). This number grew to 23,073 in 2019.

Further, the market in Asia Pacific region is estimated to witness noteworthy growth over the forecast period on the back of growing incidences of blood cancer, along with rising health awareness amongst the people. According to GLOBOCAN 2020' report by the IARC, a number of 2,41,270 non-Hodgkin lymphoma and 31,742 Hodgkin lymphoma were reported in Asia. Moreover, the increasing disposable income in the region is also estimated to propel the market growth.

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The study further incorporates Y-O-Y growth, demand & supply and forecast future opportunity in North America (U.S., Canada), Europe (U.K., Germany, France, Italy, Spain, Hungary, Belgium, Netherlands & Luxembourg, NORDIC [Finland, Sweden, Norway, Denmark], Poland, Turkey, Russia, Rest of Europe), Latin America (Brazil, Mexico, Argentina, Rest of Latin America), Asia-Pacific (China, India, Japan, South Korea, Indonesia, Singapore, Malaysia, Australia, New Zealand, Rest of Asia-Pacific), Middle East and Africa (Israel, GCC [Saudi Arabia, UAE, Bahrain, Kuwait, Qatar, Oman], North Africa, South Africa, Rest of Middle East and Africa).

The global hematopoietic stem cell transplant (HSCT) market is segmented by disease indication into lymphoproliferative disorders, leukemia, and non-malignant disorders. The leukemia segment is further divided into acute myeloid leukemia (AML), acute lymphatic leukemia (ALL), myelodysplastic syndrome (MDS), and others. Amongst these segments, the acute myeloid leukemia (AML) segment is projected to display a moderate revenue during the forecast period, backed by the rising prevalence of the disease type. For instance, it has been observed that AML makes up to about 30% of all leukemia cases amongst adults and that the average age of diagnosis of the disease is at around 68.

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The global hematopoietic stem cell transplant (HSCT) market is also segmented on the basis of transplant type into allogeneic and autologous. Amongst these segments, the allogeneic transplant segment generated the largest market share in the year 2021 and is further projected to attain a significant market revenue during the forecast period. The major factor anticipated to drive the growth of the segment is the numerous benefits associated with the process, which include the formation of a new immune system in patients undergoing this transplant type after the donated cells are engrafted into the body of the patient. Further, the autologous segment is projected to grow with a significant CAGR during the forecast period, backed by the rising availability of donors for this type of transplantation process and for the surge in the number of transplantation process by using this type. For instance, in the other statistics by the EBMT, the total number of allogeneic and autologous transplants performed in the year 2019 in Europe reached 19798 and 28714 respectively.

The global hematopoietic stem cell transplant (HSCT) market is segmented on the basis of application.

Global Hematopoietic Stem Cell Transplant (HSCT) Market, Segmentation by Application

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Some of the prominent players and their company profiling included in the report are Lonza Group Ltd., Escape Therapeutics, Inc., Regen BioPharma, Inc., ThermoGenesis Holdings, Inc., CSG-BIO Company, Inc. (CellSave), CBR Systems, Inc., Pluristem Inc., Global Cord Blood Corporation, ViaCord, LLC, Cynata Therapeutics Limited, and others. The profiling enfolds growth opportunities, challenges, market trends, competitive analysis and positioning, along with the strategies used by them to stay ahead of their competitors.

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Global Hematopoietic Stem Cell Transplant (HSCT) Market to be Driven by Increasing Prevalence of Blood Ca - Benzinga

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Stem Cell Therapy for Parkinson’s: Current Developments – Healthline

Posted: August 5, 2022 at 2:09 am

Parkinsons disease is a neurological disorder with symptoms that become more severe over time. It affects about 1% of people ages 60 years and older in industrialized nations. The exact cause of the disease isnt known, but experts believe that both genetic and environmental factors play a role.

Parkinsons disease causes neurons to die in certain parts of your brain, leading to a decrease of dopamine. Dopamine is a neurotransmitter. Cells in your brain release dopamine as a way of sending signals to other nearby cells.

When you have Parkinsons, a decrease in dopamine activity can lead to such symptoms as:

Theres no cure for Parkinsons disease. But over the past few decades, researchers have been studying stem cell therapy to provide better treatment options.

Read on to learn more about current and future developments in using stem cell therapy to treat Parkinsons disease.

Stem cells are special because theyre undifferentiated, meaning they have the potential to become many types of specialized cells.

You might think of stem cells as natural resources for your body. When your body needs a specific type of cell from bone cells to brain cells an undifferentiated stem cell can transform to fit the need.

There are three main types of stem cells:

Stem cell therapy is the use of stem cells usually from a donor, but sometimes from your own body to treat a disorder.

Because Parkinsons disease leads to the death of brain cells, researchers are trying to use stem cells to replace brain cells in the affected areas. This could help treat the symptoms of Parkinsons disease.

Researchers are exploring various approaches to use stem cells to treat Parkinsons disease.

The current idea is to introduce stem cells directly into the affected areas of your brain where they can transform into brain cells. These new brain cells could then help regulate dopamine levels, which should improve the symptoms of the disease.

Its important to note that experts believe this would only be a treatment for Parkinsons disease and not a cure.

While stem cell therapy has the potential to replace the brain cells destroyed by Parkinsons disease, the disease would still be present. Parkinsons disease would likely destroy the implanted stem cells eventually.

Its unclear right now whether stem cell therapy could be used multiple times to continue to reduce symptoms of Parkinsons disease or if the effect would be the same after multiple procedures.

Until the discovery of the process of creating iPSCs, the only stem cell therapies for Parkinsons disease required the use of embryonic stem cells. This came with ethical and practical challenges, making research more difficult.

After iPSCs became available, stem cells have been used in clinical trials for many conditions involving neural damage with overall mixed results.

The first clinical trial using iPSCs to treat Parkinsons disease was in 2018 in Japan. It was a very small trial with only seven participants. Other trials have been completed using animal models.

So far, trials have shown improvement to symptoms affecting movement as well as nonmotor symptoms such as bladder control.

Some challenges do arise from the source of the stem cells.

Stem cell therapy can be thought of as being similar to an organ transplant. If the iPSCs are derived from a donor, you may need to use immunosuppressant drugs to prevent your body from rejecting the cells.

If the iPSCs are derived from your own cells, your body might be less likely to reject them. But experts believe that this will delay stem cell therapy while the iPSCs are made in a lab. This will probably be more costly than using an established line of tested iPSCs from a donor.

There are many symptoms of Parkinsons disease. Theyre often rated using the Unified Parkinsons Disease Rating Scale (UPDRS) or the Movement Disorder Societys updated revision of that scale, the MDS-UPDRS.

Clinical trials today are generally looking to significantly improve UPDRS or MDS-UPDRS scores for people with Parkinsons disease.

Some trials are testing new delivery methods, such as intravenous infusion or topical applications. Others are looking to determine the safest number of effective doses. And other trials are measuring overall safety while using new medical devices in stem cell therapy.

This is an active area of research. Future trials will help narrow down the most safe and effective approach to stem cell therapy for Parkinsons disease.

Clinical trials are usually conducted in three phases. Each phase adds more participants, with the first phase usually limited to a few dozen people and several thousand in the third phase. The purpose is to test the treatments safety and effectiveness.

Clinical trials testing stem cell therapy for Parkinsons disease are still in the early phases. If the current trials are successful, it will likely still be 4 to 8 years before this treatment is widely available.

The goal of stem cell therapy for Parkinsons disease is to replace destroyed brain cells with healthy, undifferentiated stem cells. These stem cells can then transform into brain cells and help regulate your dopamine levels. Experts believe this can relieve many of the symptoms of Parkinsons disease.

This therapy is still in the early stages of clinical testing. Many trials are either proposed, currently recruiting, or already active. The results of these trials will determine how soon stem cell therapy might become widely available as a treatment for Parkinsons disease.

At the moment, its not believed that stem cell therapy will cure Parkinsons disease. But it might be an alternative to existing treatments such as drug therapies and deep brain stimulation.

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‘Off the shelf’ CAR T cells for cancer treatment? – Boston Children’s Answers – Boston Children’s Discoveries

Posted: August 5, 2022 at 2:09 am

In CAR T-cell immunotherapy, T cells from a patients own blood are engineered to carry so-called chimeric antigen receptors (CAR) that enable the T cells to attack and kill tumor cells. While CAR-T therapy is a powerful approach for certain leukemias and lymphomas, its not available for many patients who need it. It can be difficult to gather enough functional T cells from patients blood, and manufacturing CAR T cells for each individual patient is expensive and takes time time patients may not have on their side.

A new technique developed by the lab of George Q. Daley, MD, PhD, in the Boston Childrens Hospital Stem Cell Program could make CAR T-cell therapy more widely accessible. Using induced pluripotent stem cells (iPS cells), the researchers developed a method to make generic CAR T cells that could be produced at scale for use in multiple patients. They reported their findings in Cell Stem Cell on August 4.

We show that generic iPS cells can be converted to CAR T cells not only more efficiently, but more effectively creating an enhanced CAR T cell that more faithfully resembles the gold-standard clinical-grade cells we currently use, says Daley, the projects senior investigator and a member of the Dana-Farber/Boston Childrens Cancer and Blood Disorders Center. Our strategy could enable off-the-shelf CAR-T therapies and help more patients access these treatments.

While iPS cells are, in theory, a limitless source of different cell types, Daley, first author Ran Jing, PhD, and their colleagues had to overcome the challenge of deriving mature, fully functioning T cells from which CAR T cells could be made. In the past, researchers have struggled with this because of the tendency for iPS cells to produce immature, embryonic cells in the Petri dish.

Looking at epigenetic factors involved in blood development, the team zeroed in on the enzyme EZH1, which restricts the differentiation of mature lymphoid cells. Suppressing EZH1, they found, gave iPS cells the ability to make mature T cells. The team also developed a culture system that avoids co-culture with mouse-derived cells, which is cumbersome and yields T cells that arent sufficiently mature.

When the iPS-cell-derived T cells were further transformed into CAR T cells, they showed anti-tumor activity comparable to that of CAR T cells derived by methods currently used for clinical therapies. These new cells had an enhanced ability to kill cancer cells in the lab and to clear cancer cells in live mice when compared to T cells made with prior iPS-cell methods.

After many years of promise, it seems that iPS cells are finally yielding new therapeutic approaches to the treatment of diseases like cancer, says Daley.

Boston Childrens and ElevateBio, a technology-driven company focused on cell and gene therapy development, are forming a new company (not yet named) around the technology. The study was supported by grants from the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Emerson Collective Cancer Research Fund.

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'Off the shelf' CAR T cells for cancer treatment? - Boston Children's Answers - Boston Children's Discoveries

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Inflammation accelerates aging of the hematopoietic system – EurekAlert

Posted: August 5, 2022 at 2:09 am

In mice, inflammation in early to mid-life leads to a permanent decline in functional blood stem cells, according to a recent publication by scientists from the German Cancer Research Center (DKFZ) and the Stem Cell Institute HI-STEM*. The ability of the blood stem cells to regenerate was suppressed for at least one year after challenge with inflammation, suggesting that infection and inflammation may act as a prominent driver of age-associated functional decline in tissues. In line with this, mice exposed to such challenges in early life developed clinically relevant features of aging that are often observed in elderly humans.

Blood stem cells in the bone marrow provide a lifelong replenishment of the different cell types making up the blood system. In addition, they are also of capable of making new stem cells, in a process called self-renewal. In older people, diseases of the hematopoietic system often occur, such as anemia or certain forms of blood cancer. Such diseases are thought to be caused by an age-associated decline in stem cell self-renewal. However, mouse models housed under highly controlled, pathogen-free conditions, rarely spontaneously develop such age-related diseases.

According to experts, the cause of this age-related loss of function of the hematopoietic system is a chronic low-grade inflammatory condition called inflammaging, that only develops in later life and impairs the function blood stem cells. However, the question that we wanted to answer was whether inflammation and infections in early life can permanently damage blood stem cells and thus promote aging of the blood system, says Mick Milsom of the German Cancer Research Center and the Stem Cell Institute HI-STEM. "We have therefore carried out time-consuming experiments to determine for how we observe an inhibitory effect on stem cell function following infection and inflammation, and came to the surprising conclusion that we never see any evidence of stem cell recovery, suggesting that this process is long-lasting or perhaps even irreversible."

Mice were challenged several times with a pro-inflammatory substance or bacteria, with four-week intervals between injections. The lack of stem cell recovery between each round of challenge meant that these treatments resulted in an additive inhibitory effect, supporting a model that explains age-associated tissue dysfunction and disease: where separate instances of infection or inflammation can have a cumulative inhibitory effect on stem cell function, even if separated by months or years.

The researchers subsequently identified the cause of the dysfunctional hematopoiesis: Blood stem cells failed to self-renew as they were forced to divide in response to the inflammatory stimuli. The long-term consequence of a lack of self-renewal is that the hematopoietic system becomes exhausted. "This observation in mice contradicts common doctrine: we had previously believed that, after inflammatory challenge, blood stem cells revert into a so-called dormant state that preserves their capacity for self-renewal," says Milsom, explaining this surprising aspect of his work.

Importantly, the inflammation in young mice led to persistent changes in the hematopoietic system resembling age-related changes often found in elderly people. These include anemia and decreased number of cells in the bone marrow. "Inflammation and infection at a young age appear to accelerate the aging of the hematopoietic system," Milsom said, summarizing the findings. "Our next challenge is to explore whether prophylactic anti-inflammatory treatment could delay the development of age-related diseases of the blood system, while still preserving the immune response against pathogens."

Ruzhica Bogeska, Ana-Matea Mikecin, Paul Kaschutnig, Malak Fawaz, , Marleen Bchler-Schff, Duy Le, Miguel Ganuza, Angelika Vollmer, Stella V. Paffenholz, Noboru Asada, Esther Rodriguez-Correa, Felix Frauhammer, Florian Buettner, Melanie Ball, Julia Knoch, Sina Stble, Dagmar Walter, Amelie Petri, Martha J. Carreo-Gonzalez, Vinona Wagner, Benedikt Brors, Simon Haas, Daniel B. Lipka, Marieke A.G. Essers, Vivienn Weru, Tim Holland-Letz, Jan-Philipp Mallm, Karsten Rippe, Stephan Krmer, Matthias Schlesner, Shannon McKinney Freeman, Maria Carolina Florian, Katherine Y. King, Paul S. Frenette, Michael A. Rieger, Michael D. Milsom:

Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.

CELL Stem Cell 2022, DOI: 10.1016/j.stem.2022.06.012

Share Link: https://authors.elsevier.com/a/1fRPY6tu0CiH2q

(valid until September 7, 2022)

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Wrttemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Cell Therapy Technologies Market worth $8.0 billion by 2027 – Exclusive Report by MarketsandMarkets – PR Newswire

Posted: August 5, 2022 at 2:09 am

CHICAGO, Aug. 3, 2022 /PRNewswire/ --Cell Therapy Technologies Marketis projected to grow from USD 4.0 billion in 2022 to USD 8.0 billion by 2027, at a CAGR of 14.6% from 2022 to 2027, according to a new report by MarketsandMarkets.Growth in the market can be attributed to number of cell therapy clinical trials related to cancer. Furthermore, increasing incidence of communicable diseases and the growing risk of pandemics are also expected to fuel the market growth.

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Browse in-depth TOC on "Cell Therapy Technologies Market"202 Tables48 Figures218 Pages

The cell therapy equipment segment accounted for the second largest share of the product segment in the cell therapy technologies market in 2021.

The second largest share of cell therapy equipment segment can be attributed to the growing demand for these equipments. Cell therapy equipment is used in cell processing (such as cell isolation, expansion, and harvesting), cell preservation and handling, and process monitoring and quality control. The segment market is further sub-segmented into cell processing equipment, single-use equipment, and other equipment (flow cytometers, cell counters, microscopes, etc).

The stem cells segment accounted for the second largest share of the cell type segment in the cell therapy technologies market in 2021.

Rising awareness regarding the use of stem cells in the treatment of various diseases and the growing focus of players on stem cell research are driving the growth of this market segment. Rising collaboration between universities and biotechnology & biopharmaceutical companies for stem cell research and government support (availability of funding) are other important drivers.

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The Asia Pacific region is the fastest-growing region of the cell therapy technologies market in 2021.

The Asia Pacific is estimated to be the fastest-growing segment of the market. The growth of the market of the region is mostly driven by their low labor and manufacturing costs, which has drawn huge investments by biopharma giants to these countries. The increasing disposable income, growing prevalence of lifestyle and age-related chronic diseases also contribute to the high growth of the regional market.

Key players in the cell therapy technologies market include Thermo Fisher Scientific, Inc. (US), Merck KGaA (Germany), Danaher Corporation (US), Lonza Group (Switzerland), Sartorius AG (Germany), Terumo BCT (US), Becton, Dickinson and Company (US), Fresenius SE & Co. KGaA (Germany), Avantor, Inc. (US), Bio-Techne Corporation (US), Corning Incorporated (US), FUJIFILM Irvine Scientific (US), MaxCyte Inc. (US), Werum IT Solutions GmbH (Germany), RoosterBio Inc. (US), SIRION Biotech GmbH (Germany), TrakCel (UK), L7 Informatics, Inc. (US), Miltenyi Biotec GmbH (Germany), STEMCELL Technologies (Canada), GPI Iberia (Spain), MAK-SYSTEM (US), OrganaBio, LLC (US), IxCells Biotechnology (China), and Wilson Wolf Manufacturing Corporation (US).

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New patent-pending method mass-produces antitumor cells to treat blood diseases and cancer – Purdue University

Posted: August 5, 2022 at 2:09 am

WEST LAFAYETTE, Ind. A Purdue University chemical engineer has improved upon traditional methods to produce off-the-shelf human immune cells that show strong antitumor activity, according to a paper published in the peer-reviewed journal Cell Reports.

Xiaoping Bao, a Purdue University assistant professor from the Davidson School of Chemical Engineering, said CAR-neutrophils, or chimeric antigen receptor neutrophils, and engraftable HSCs, or hematopoietic stem cells, are effective types of therapies for blood diseases and cancer. Neutrophils are the most abundant white cell blood type and effectively cross physiological barriers to infiltrate solid tumors. HSCs are specific progenitor cells that will replenish all blood lineages, including neutrophils, throughout life.

These cells are not readily available for broad clinical or research use because of the difficulty to expand ex vivo to a sufficient number required for infusion after isolation from donors, Bao said. Primary neutrophils especially are resistant to genetic modification and have a short half-life.

Bao has developed a patent-pending method to mass-produce CAR-neutrophils from human pluripotent stem cells (hPSCs), that is, cells that self-renew and are able to become any type of human cell. The chimeric antigen receptor constructs were engineered to express on the surface of the hPSCs, which were directed into functional CAR-neutrophils through a novel, chemically defined protocol.

The method was created in collaboration with Qing Deng at Purdue's Department of Biological Sciences, Hal E. Broxmeyer, now deceased, at Indiana University School of Medicine, and Xiaojun Lian at the Pennsylvania State University.

We developed a robust protocol for massive production of de novo neutrophils from human pluripotent stem cells, Bao said. These hPSC-derived neutrophils displayed superior and specific antitumor activities against glioblastoma after engineering with chimeric antigen receptors.

Bao disclosed the innovation to the Purdue Research Foundation Office of Technology Commercialization, which has applied for an international patent under the Patent Cooperation Treaty system of the World Intellectual Property Organization. The innovation has been optioned to an Indiana-headquartered life sciences company.

We will also work with Dr. Timothy Bentley, professor of neurology and neurosurgery,and his team at the Purdue College of Veterinary Medicine to run clinical trials in pet dogs with spontaneous glioma, Bao said.

This research project was partially supported by the Davidson School of Chemical Engineering and College of Engineering Startup Funds, Purdue Center for Cancer Research, Showalter Research Trust and federal grants from the National Science Foundation and National Institute of General Medical Sciences.

About Purdue University

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Writer: Steve Martin, sgmartin@prf.org

Source: Xiaoping Bao, bao61@purdue.edu

ABSTRACT

Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy

Yun Chang, Ramizah Syahirah, Xuepeng Wang, Gyuhyung Jin, Sandra Torregrosa-Allen, Bennett D. Elzey, Sydney N. Hummel, Tianqi Wang, Can Li, Xiaojun Lian, Qing Deng, Hal E. Broxmeyer, Xiaoping Bao

Neutrophils, the most abundant white blood cells in circulation, are closely related to cancer development and progression. Healthy primary neutrophils present potent cytotoxicity against various cancer cell lines through direct contact and via generation of reactive oxygen species. However, due to their short half-life and resistance to genetic modification, neutrophils have not yet been engineered with chimeric antigen receptors (CARs) to enhance their antitumor cytotoxicity for targeted immunotherapy. Here, we genetically engineered human pluripotent stem cells with synthetic CARs and differentiated them into functional neutrophils by implementing a chemically-defined platform. The resulting CAR-neutrophils presented superior and specific cytotoxicity against tumor cells both in vitro and in vivo. Collectively, we established a robust platform for massive production of CAR-neutrophils, paving the way to myeloid cell-based therapeutic strategies that would boost current cancer treatment approaches.

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New patent-pending method mass-produces antitumor cells to treat blood diseases and cancer - Purdue University

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Twenty-Five Years After My House Call To Dolly: What Have We Learned About Cloning And How Did We Learn It? – Forbes

Posted: August 5, 2022 at 2:09 am

Twenty-five years ago, the scientific breakthrough of mammalian cloning marked a monumental moment in medicine and science. Anticipating the collision it would have with ethical decision making in medicine, I, the only physician-scientist in the U.S. Senate at the time, journeyed to the University of Edinburgh in Scotland to personally visit Sir Ian Wilmut at his research lab at the Roslin Institute.

My house call to Dolly in 1997: I stand with Dolly, the first ever mammal to be cloned from an adult ... [+] somatic cell, during my journey to visit her creator and caretaker, Sir Ian Wilmut.

Professor Wilmut just months before in 1996 had cloned a sheep from an adult somatic cell, shocking the world. This was the first successful attempt of its kind. All over the world people were wondering: would we be cloning a human being next? We talked science, we talked ethics, and we talked about his creations potential impact on altering the course of human history. I also met and examined the cloned sheep, Dolly, in her stall.

Dolly, named after Tennessees own Dolly Parton, was a Finnish Dorset sheep cloned from a single, adult mammary gland cell. Her creation, birth, and short life were scientific feats that immediately sparked global concern and discourse on the increasingly complex moral and ethical dilemmas posed by a sudden discovery of life-manipulating science.

Wilmut and colleagues published their achievement in February 1997, having kept Dolly secret for seven months. We, as a society, were quickly forced to answer difficult, probing questions. A few months later on the Senate floor, I borrowed a question that the Washington Post editorial board had posed a few years before: Is there a line that should not be crossed even for scientific or other gain, and if so where is it?

Here are my remarks in the Senate chamber in 1998:

So it is vital that our public debate and reflection on scientific developments keep pace, and even anticipate and prepare for new scientific knowledge. The moral and ethical dilemmas inherent in the cloning of human beings may well be our greatest test to date. We do not simply seek knowledge, but the wisdom to apply that knowledge. As with each of the mind-boggling scientific advances of the last century, we know that there is the potential for both good and evil in this technology. Congressional Record February 2, 1998

Years removed, I now reflect back on the confusion, questions, and status quo that Dolly challenged.

Dolly was the first mammal to be successfully cloned from an adult somatic cell, which is any type of bodily cell that is not a reproductive germ cell. The process Wilmut developed is technically called somatic cell nuclear transfer, colloquially known as cloning. It is the process of transferring the nuclear DNA of a donor somatic cell into an enucleated oocyte, followed by embryo development and then transfer to a surrogate recipient, followed by live birth.

Dollys creation in a test tube and eventual birth marked a major milestone in scientific research, suggesting that an animal could be cloned to create an exact replica using genetic material derived from theoretically any type of body cell. It opened the world to staggering new possibilities in reproductive cloning and therapeutic cloning.

Soon after Dollys birth, another parallel and similarly monumental finding was made: in 1998 embryonic stem cells were discovered. These cells are a highly unique type of unprogrammed somatic cell with the exceptional ability to both reproduce unlimited exact copies of themselves and develop into more specialized cell types, such as heart, lung, kidney or skin cells. And though seemingly miraculous in potential, these cells could not be created or programmed from any other type of cell and could only be collected from embryos an ethical dilemma because collection for research required destruction of the embryo itself.

Dolly changed this. Her successful creation paved the way for future scientists to develop a technique to independently produce equally powerful pluripotent stem cells by reprogramming other adult somatic cells, revolutionizing genetic therapy, and completely nullifying the ethical dilemma of collecting embryonic stem cells from embryos. Similarly, Dolly also highlighted the potential for scientists to create new tissues and organs for diseased patients, and to preserve the genetic material of endangered species.

But, along with these positive contributions came widespread concern about the ethics of cloning, especially around potential attempts to clone another human being. Many, including myself, feared this type of technology, if left unregulated, would be misused and abused. Indeed, cloning evoked great scientific power that demanded even greater ethical responsibility, and there were no established ethical guardrails at the time to monitor this duty.

In retrospect, these fears have diminished in part due to proactive measures and to the inherent complexities of the human genome (cloning an entire human being is, after all, a large jump from cloning a sheep). Importantly, legislative and scientific communities have been resolute and unified in their opposition to cloning human beings.

Though a human embryo was indeed successfully cloned in 2013, no known progress has been made when it comes to attempts to clone a human being. Yet the technique to create Dolly has been repurposed widely and has led to numerous scientific innovations.

In 2003, six years after her birth, Dolly became sick and was euthanized. Her decline in health was due to the development of tumors in her chest; some examinations of her cells suggested that she was also aging prematurely.

Despite her relatively short life (the average sheep lifespan is ~10-12 years), Dollys influence on the scientific community has been profound. Not only did she force scientists and researchers to redefine the ethics of their field, but she also laid the foundation for other significant scientific advancements in the fast-evolving new field we know today as regenerative medicine.

One powerful example is gene therapy and editing, where specific genes are targeted, edited, and repaired to protect against disease, cancer, autoimmune disorders, and even rewiring immune system cells for treatment-resistant cancer patients. This revolutionary innovation is made possible by CRISPR technology (the same technology that enabled rapid vaccine development for COVID-19), which is currently celebrating its 10-year anniversary.

Genetic cloning was also made possible thanks to Dolly. This is a type of cloning where scientists create copies of genes within DNA segments to combine with plasmid DNA, or self-replicating genetic material, and then place this new plasmid into a host organism, such as a bacterium, yeast, or mammal cell. This process is used to develop vaccines and antigen tests and is also used to identify useful genetic traits in plants, which can be replicated on a larger scale through the genetic modification of seeds.

Further, cloning techniques have also helped to advance agricultural practices. Farmers can use cloning technology to quickly introduce favored characteristics of prize livestock (such as the ability to produce large amounts of high-quality milk) into a herd by cloning and breeding. These livestock will then further reproduce using traditional breeding or assisted reproductive technology.

Despite advances in genetic cloning and agricultural practices, cloning especially the additional attempts at cloning whole organisms remains variable and highly inefficient.

Successful attempts have been made by companies like Sooam Biotech Research and ViaGen Pets to clone dogs and kittens for wealthy pet owners. But, even today, the success rate of animal cloning is estimated to be less than 30%. In fact, many animal rights activists oppose the practice citing animal welfare. In 2015, the European Union banned the practice of livestock cloning.

Overall interest in cloning slowed as advances in adult stem cell research gained traction in the 2000s. This resulted primarily from scientists newfound ability to take adult human cells, for example skin cells, and reprogram them back into an earlier, more primitive but more powerful embryonic-like, pluripotent cells.

This technique was pioneered by Japanese scientist Shinya Yamanaka in 2006, for which he was awarded the 2012 Nobel Prize in Physiology or Medicine. Yamanakas discovery of reprogramming already specialized adult cells to create induced pluripotent stem cells (IPS) took the ethical issue of destroying embryos for research off the table. Some scientists continue to look to cloning as a way to develop genetically unique stem cells that can be used to reduce the risk of triggering an immune response.

Notes taken shortly after my visit with Dolly: "She has been seen by 2.5 billion people."

We have come a long way since my exploratory journey from the Senate floor in Washington, DC, to the stall and research laboratory that housed Dolly in Edinburgh in 1997.

For all the controversy that Dolly sparked during her short life, her contributions to society have been nothing short of remarkable. She forced thought leaders, researchers, and policymakers around the world to confront the ethics of cloning. And, she encouraged us, as a society, to weigh in and engage on the ethical considerations of increasingly frequent scientific discoveries.

On all of these fronts, we worked tirelessly to instill and adhere to a strong scientific code, focusing on the bettering of science, innovation, and technology for societal good. Cloning gave us that first glimpse into the future.

As I said on the floor of the Senate on February 3, 1998:

This cloning debate, I think, maybe for the first time in the history of this body [the US Senate], forces us to address what is inevitable as we look to the future, and that is a rapid-fire, one-after-another onslaught of new scientific technological innovation that has to be assimilated into our ethical-social fabric. Congressional Record February 3, 1998

What I said then still holds true today, Science and ethics must march hand in hand. Congressional Record February 11, 1998

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Twenty-Five Years After My House Call To Dolly: What Have We Learned About Cloning And How Did We Learn It? - Forbes

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Whatever Happened to the Transhumanists? – Gizmodo

Posted: August 5, 2022 at 2:06 am

Image: Gizmodo/Shutterstock

Gizmodo is 20 years old! To celebrate the anniversary, were looking back at some of the most significant ways our lives have been thrown for a loop by our digital tools.

Like so many others after 9/11, I felt spiritually and existentially lost. Its hard to believe now, but I was a regular churchgoer at the time. Watching those planes smash into the World Trade Center woke me from my extended cerebral slumber and I havent set foot in a church since, aside from the occasional wedding or baptism.

I didnt realize it at the time, but that godawful day triggered an intrapersonal renaissance in which my passion for science and philosophy was resuscitated. My marriage didnt survive this mental reboot and return to form, but it did lead me to some very positive places, resulting in my adoption of secular Buddhism, meditation, and a decade-long stint with vegetarianism. It also led me to futurism, and in particular a brand of futurism known as transhumanism.

Transhumanism made a lot of sense to me, as it seemed to represent the logical next step in our evolution, albeit an evolution guided by humans and not Darwinian selection. As a cultural and intellectual movement, transhumanism seeks to improve the human condition by developing, promoting, and disseminating technologies that significantly augment our cognitive, physical, and psychological capabilities. When I first stumbled upon the movement, the technological enablers of transhumanism were starting to come into focus: genomics, cybernetics, artificial intelligence, and nanotechnology. These tools carried the potential to radically transform our species, leading to humans with augmented intelligence and memory, unlimited lifespans, and entirely new physical and cognitive capabilities. And as a nascent Buddhist, it meant a lot to me that transhumanism held the potential to alleviate a considerable amount of suffering through the elimination of disease, infirmary, mental disorders, and the ravages of aging.

The idea that humans would transition to a posthuman state seemed both inevitable and desirable, but, having an apparently functional brain, I immediately recognized the potential for tremendous harm. Wanting to avoid a Brave New World dystopia (perhaps vaingloriously), I decided to get directly involved in the transhumanist movement in hopes of steering it in the right direction. To that end, I launched my blog, Sentient Developments, joined the World Transhumanist Association (now Humanity+), co-founded the now-defunct Toronto Transhumanist Association, and served as the deputy editor of the transhumanist e-zine Betterhumans, also defunct. I also participated in the founding of the Institute for Ethics and Emerging Technologies (IEET), on which I continue to serve as chairman of the board.

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Indeed, it was also around this time in the early- to mid-2000s that I developed a passion for bioethics. This newfound fascination, along with my interest in futurist studies and outreach, gave rise to a dizzying number of opportunities. I gave talks at academic conferences, appeared regularly on radio and television, participated in public debates, and organized transhumanist-themed conferences, including TransVision 2004, which featured talks by Australian performance artist Stelarc, Canadian inventor and cyborg Steve Mann, and anti-aging expert Aubrey de Grey.

The transhumanist movement had permeated nearly every aspect of my life, and I thought of little else. It also introduced me to an intriguing (and at times problematic) cast of characters, many of whom remain my colleagues and friends. The movement gathered steady momentum into the late 2000s and early 2010s, acquiring many new supporters and a healthy dose of detractors. Transhumanist memes, such as mind uploading, genetically modified babies, human cloning, and radical life extension, flirted with the mainstream. At least for a while.

The term transhumanism popped into existence during the 20th century, but the idea has been around for a lot longer than that.

The quest for immortality has always been a part of our history, and it probably always will be. The Mesopotamian Epic of Gilgamesh is the earliest written example, while the Fountain of Youththe literal Fountain of Youthwas the obsession of Spanish explorer Juan Ponce de Len.

Notions that humans could somehow be modified or enhanced appeared during the European Enlightenment of the 18th century, with French philosopher Denis Diderot arguing that humans might someday redesign themselves into a multitude of types whose future and final organic structure its impossible to predict, as he wrote in DAlemberts Dream. Diderot also thought it possible to revive the dead and imbue animals and machines with intelligence. Another French philosopher, Marquis de Condorcet, thought along similar lines, contemplating utopian societies, human perfectibility, and life extension.

The Russian cosmists of the late 19th and early 20th centuries foreshadowed modern transhumanism, as they ruminated on space travel, physical rejuvenation, immortality, and the possibility of bringing the dead back to life, the latter being a portend to cryonicsa staple of modern transhumanist thinking. From the 1920s through to the 1950s, thinkers such as British biologist J. B. S. Haldane, Irish scientist J. D. Bernal, and British biologist Julian Huxley (who popularized the term transhumanism in a 1957 essay) were openly advocating for such things as artificial wombs, human clones, cybernetic implants, biological enhancements, and space exploration.

It wasnt until the 1990s, however, that a cohesive transhumanist movement emerged, a development largely brought about byyou guessed itthe internet.

As with many small subcultures, the internet allowed transhumanists around the world to start communicating on email lists, and then websites and blogs, James Hughes, a bioethicist, sociologist, and the executive director of the IEET, told me. Almost all transhumanist culture takes place online. The 1990s and early 2000s were also relatively prosperous, at least for the Western countries where transhumanism grew, so the techno-optimism of transhumanism seemed more plausible.

The internet most certainly gave rise to the vibrant transhumanist subculture, but the emergence of tantalizing, impactful scientific and technological concepts is what gave the movement its substance. Dolly the sheep, the worlds first cloned animal, was born in 1996, and in the following year Garry Kasparov became the first chess grandmaster to lose to a supercomputer. The Human Genome Project finally released a complete human genome sequence in 2003, in a project that took 13 years to complete. The internet itself gave birth to a host of futuristic concepts, including online virtual worlds and the prospect of uploading ones consciousness into a computer, but it also suggested a possible substrate for the Nospherea kind of global mind envisioned by the French Jesuit philosopher Pierre Teilhard de Chardin.

Key cheerleaders contributed to the proliferation of far-flung futurist-minded ideas. Eric Drexlers seminal book Engines of Creation (1986) demonstrated the startling potential for (and peril of) molecular nanotechnology, while the work of Hans Moravec and Kevin Warwick did the same for robotics and cybernetics, respectively. Futurist Ray Kurzweil, through his law of accelerating returns and fetishization of Moores Law, convinced many that a radical future was at hand; in his popular books, The Age of Spiritual Machines (1999) and The Singularity is Near (2005), Kurzweil predicted that human intelligence was on the cusp of merging with its technology. In his telling, this meant that we could expect a Technological Singularity (the emergence of greater-than-human artificial intelligence) by the mid-point of the 21st century (as an idea, the Singularityanother transhumanist staplehas been around since the 1960s and was formalized in a 1993 essay by futurist and sci-fi author Vernor Vinge). In 2006, an NSF-funded report, titled Managing Nano-Bio-Info-Cogno Innovations: Converging Technologies in Society, showed that the U.S. government was starting to pay attention to transhumanist ideas.

A vibrant grassroots transhumanist movement developed at the turn of the millennium. The Extropy Institute, founded by futurist Max More, and the World Transhumanist Association (WTA), along with its international charter groups, gave structure to what was, and still is, a wildly divergent set of ideas. A number of specialty groups with related interests also emerged, including: the Methuselah Foundation, the Singularity Institute for Artificial Intelligence (now the Machine Intelligence Research Institute), the Center for Responsible Nanotechnology, the Foresight Institute, the Lifeboat Foundation, and many others. Interest in cryonics increased as well, with the Alcor Life Extension Foundation and the Cryonics Institute receiving more attention than usual.

Society and culture got cyberpunked in a hurry, which naturally led people to think increasingly about the future. And with the Apollo era firmly in the rear view mirror, the publics interest in space exploration waned. Bored of the space-centric 2001: A Space Odyssey and Star Wars, we increasingly turned our attention to movies about AI, cybernetics, and supercomputers, including Blade Runner, Akira, and The Matrix, many of which had a distinctive dystopian tinge.

With the transhumanist movement in full flight, the howls of outrage became louderfrom critics within the conservative religious right through to those on the anti-technological left. Political scientist Francis Fukuyama declared transhumanism to be the worlds most dangerous idea, while bioethicist Leon Kass, a vocal critic of transhumanism, headed-up President George W. Bushs bioethics council, which explicitly addressed medical interventions meant to enhance human capabilities and appearance. The bioethical battle lines of the 21st century, it appeared, were being drawn before our eyes.

This TIME cover blew my mind when it came out on February 21, 2011.Image: Photo-illustration by Phillip Tolendo for TIME. Prop Styling by Donnie Myers.

It was a golden era for transhumanism. Within a seemingly impossible short time, our ideas went from obscurity to tickling the zeitgeist. The moment that really did it for me was seeing the cover of TIMEs February 21, 2011, issue, featuring the headline, 2045: The Year Man Becomes Immortal, and cover art depicting a brain-jacked human head.

By 2012, my own efforts in this area had landed me a job as a contributing editor for io9, which served to expand my interest in science, futurism, and philosophy even further. I presented a talk at Moogfest in 2014 and had some futurist side hustles, serving as the advisor for National Geographics 2017 documentary-drama series, Year Million. Transhumanist themes permeated much of my work back then, whether at io9 or later with Gizmodo, but less so with each passing year. These days I barely write about transhumanism, and my involvement in the movement barely registers. My focus has been on spaceflight and the ongoing commercialization of space, which continues to scratch my futurist itch.

What was once a piercing roar has retreated to barely discernible background noise. Or at least thats how it currently appears to me. For reasons that are both obvious and not obvious, explicit discussions of transhumanism and transhumanists have fallen by the wayside.

The reason we dont talk about transhumanism as much as we used to is that much of it has become a bit normalat least as far as the technology goes, as Anders Sandberg, a senior research fellow from the Future of Humanity Institute at the University of Oxford, told me.

We live lives online using wearable devices (smartphones), aided by AI and intelligence augmentation, virtual reality is back again, gene therapy and RNA vaccines are a thing, massive satellite constellations are happening, drones are becoming important in warfare, trans[gender] rights are a big issue, and so on, he said, adding: We are living in a partially transhuman world. At the same time, however, the transhumanist idea to deliberately embrace the change and try to aim for such a future has not become mainstream, Sandberg said.

His point about transhumanism having a connection to trans-rights may come as a surprise, but the futurist linkage to LGBTQ+ issues goes far back, whether it be sci-fi novelist Octavia Butler envisioning queer families and greater gender fluidity or feminist Donna Haraway yearning to be a cyborg rather than a goddess. Transhumanists have long advocated for a broadening of sexual and gender diversity, along with the associated rights to bodily autonomy and the means to invoke that autonomy. In 2011, Martine Rothblatt, the billionaire transhumanist and transgender rights advocate, took it a step further when she said, we cannot be surprised that transhumanism arises from the groins of transgenderism, and that we must welcome this further transcendence of arbitrary biology.

Natasha Vita-More, executive director of Humanity+ and an active transhumanist since the early 1980s, says ideas that were foreign to non-transhumanists 20 years ago have been integrated into our regular vocabulary. These days, transhumanist-minded thinkers often reference concepts such as cryonics, mind uploading, and memory transfer, but without having to invoke transhumanism, she said.

Is it good that we dont reference transhumanism as much anymore? No, I dont think so, but I also think it is part of the growth and evolution of social understanding in that we dont need to focus on philosophy or movements over technological or scientific advances that are changing the world, Vita-More told me. Moreover, people today are far more knowledgeable about technology than they were 20 years ago and are more adept at considering the pros and cons of change rather than just the cons or potential bad effects, she added.

PJ Manney, futurist consultant and author of the transhumanist-themed sci-fi Phoenix Horizon trilogy, says all the positive and optimistic visions of future humanity are being tempered or outright dashed as we see humans taking new tools and doing what humans do: the good, the bad, and the ugly.

Indeed, were a lot more cynical and wary of technology than we were 20 years ago, and for good reasons. The Cambridge Analytica data scandal, Edward Snowdens revelations about government spying, and the emergence of racist policing software were among an alarming batch of reproachable developments that demonstrated technologys potential to turn sour.

We dont talk about transhumanism that much any more because so much of it is in the culture already, Manney, who serves with me on the IEET board of directors, continued, but we exist in profound future shock and with cultural and social stresses all around us. Manney referenced the retrograde SCOTUS reversals and how U.S. states are removing human rights from acknowledged humans. She suggests that we secure human rights for humans before we consider our silicon simulacrums.

Nigel Cameron, an outspoken critic of transhumanism, said the futurist movement lost much of its appeal because the naive framing of the enormous changes and advances under discussion got less interesting as the distinct challenges of privacy, automation, and genetic manipulation (e.g. CRISPR) began to emerge. In the early 2000s, Cameron led a project on the ethics of emerging technologies at the Illinois Institute of Technology and is now a Senior Fellow at the University of Ottawas Institute on Science, Society and Policy.

Sandberg, a longstanding transhumanist organizer and scholar, said the War on Terror and other emerging conflicts of the 2000s caused people to turn to here-and-now geopolitics, while climate change, the rise of China, and the 2008 financial crisis led to the pessimism seen during the 2010s. Today we are having a serious problem with cynicism and pessimism paralyzing people from trying to fix and build things, Sandberg said. We need optimism!

Some of the transhumanist groups that emerged in the 1990s and 2000s still exist or evolved into new forms, and while a strong pro-transhumanist subculture remains, the larger public seems detached and largely disinterested. But thats not to say that these groups, or the transhumanist movement in general, didnt have an impact.

The various transhumanist movements led to many interesting conversations, including some bringing together conservatives and progressives into a common critique, said Cameron.

I think the movements had mainly an impact as intellectual salons where blue-sky discussions made people find important issues they later dug into professionally, said Sandberg. He pointed to Oxford University philosopher and transhumanist Nick Bostrom, who discovered the importance of existential risk for thinking about the long-term future, which resulted in an entirely new research direction. The Center for the Study of Existential Risk at the University of Cambridge and the Future of Humanity Institute at Oxford are the direct results of Bostroms work. Sandberg also cited artificial intelligence theorist Eliezer Yudkowsky, who refined thinking about AI that led to the AI safety community forming, and also the transhumanist cryptoanarchists who did the groundwork for the cryptocurrency world, he added. Indeed, Vitalik Buterin, a co-founder of Ethereum, subscribes to transhumanist thinking, and his father, Dmitry, used to attend our meetings at the Toronto Transhumanist Association.

According to Manney, various transhumanist-driven efforts inspired a vocabulary and creative impulse for many, including myself, to wrestle with the philosophical, technological and artistic implications that naturally arise. Sci-fi grapples with transhumanism now more than ever, whether people realize it or not, she said. Fair point. Shows like Humans, Orphan Black, Westworld, Black Mirror, and Upload are jam-packed with transhumanist themes and issues, though the term itself is rarelyif everuttered. That said, these shows are mostly dystopian in nature, which suggests transhumanism is mostly seen through gray-colored glasses. To be fair, super-uplifting portrayals of the future rarely work as Hollywood blockbusters or hit TV shows, but its worth pointing out that San Junipero is rated as among the best Black Mirror episodes for its positive portrayal of uploading as a means to escape death.

For the most part, however, transhuman-flavored technologies are understandably scary and relatively easy to cast in a negative light. Uncritical and starry-eyed transhumanists, of which there are many, werent of much help. Manney contends that transhumanism itself could use an upgrade. The lack of consideration for consequences and follow-on effects, as well as the narcissistic demands common to transhumanism, have always been the downfall of the movement, she told me. Be careful what you wish foryou may get it. Drone warfare, surveillance societies, deepfakes, and the potential for hackable bioprostheses and brain chips have made transhumanist ideas less interesting, according to Manney.

Like so many other marginal social movements, transhumanism has had an indirect influence by widening the Overton window [also known as the window of discourse] in policy and academic debates about human enhancement, Hughes explained. In the 2020s, transhumanism still has its critics, but it is better recognized as a legitimate intellectual position, providing some cover for more moderate bioliberals to argue for liberalized enhancement policies.

Transhumanist Anders Sandberg circa 1998. Photo: Anders Sandberg

Sandberg brought up a very good point: Nothing gets older faster than future visions. Indeed, many transhumanist ideas from the 1990s now look quaint, he said, pointing to wearable computers, smart drinks, imminent life extension, and all that internet utopianism. That said, Sandberg thinks the fundamental vision of transhumanism remains intact, saying the human condition can be questioned and changed, and we are getting better at it. These days, we talk more about CRISPR (a gene-editing tool that came into existence in 2012) than we do nanotechnology, but transhumanism naturally upgrades itself as new possibilities and arguments show up, he said.

Vita-More says the transhumanist vision is still desirable and probably even more so because it has started to make sense for many. Augmented humans are everywhere, she said, from implants, smart devices that we use daily, human integration with computational systems that we use daily, to the hope that one day we will be able to slow down memory loss and store or back-up our neurological function in case of memory loss or diseases of dementia and Alzheimers.

The observation that transhumanism has started to make sense for many is a good one. Take Neuralink, for example. SpaceX CEO Elon Musk based the startup on two very transhumanistic principlesthat interfaces between the brain and computers are possible and that artificial superintelligence is coming. Musk, in his typical fashion, claims a philanthropic motive for wanting to build neural interface devices, as he believes boosted brains will protect us from malign machine intelligence (I personally think hes wrong, but thats another story).

For Cameron, transhumanism looks as frightening as ever, and he honed in on a notion he refers to as the hollowing out of the human, the idea that all that matters in Homo sapiens can be uploaded as a paradigm for our desiderata. In the past, Cameron has argued that if machine intelligence is the model for human excellence and gets to enhance and take over, then we face a new feudalism, as control of finance and the power that goes with it will be at the core of technological human enhancement, and democracywill be dead in the water.

That being said, and despite these concerns, Manny believes theres still a need for a transhumanist movement, but one that addresses complexity and change for all humanity.

Likewise, Vita-More says a transhumanist movement is still needed because it serves to facilitate change and support choices based on personal needs that look beyond binary thinking, while also supporting diversity for good.

There is always a need for think tanks. While there are numerous futurist groups that contemplate the future, they are largely focused on energy, green energy, risks, and ethics, said Vita-More. Few of these groups are a reliable source of knowledge or information about the future of humanity other than a postmodernist stance, which is more focused on feminist studies, diversity, and cultural problems. Vita-More currently serves as the executive director of Humanity+.

Hughes says that transhumanists fell into a number of political, technological, and even religious camps when they tried to define what they actually wanted. The IEET describes its brand of transhumanism as technoprogressivisman attempt to define and promote a social democratic vision of an enhanced future, as Hughes defines it. As a concept, technoprogressivism provides a more tangible foundation for organizing than transhumanism, says Hughes, so I think we are well beyond the possibility of a transhumanist movement and will now see the growth of a family of transhumanist-inspired or influenced movements that have more specific identities, including Mormon and other religious transhumanists, libertarians and technoprogressives, and the ongoing longevist, AI, and brain-machine subcultures.

I do think we need public intellectuals to be more serious about connecting the dots, as technologies continue to converge and offer bane and blessing to the human condition, and as our response tends to be uncritically enthusiastic or perhaps unenthusiastic, said Cameron.

Sandberg says transhumanism is needed as a counterpoint to the pervasive pessimism and cynicism of our culture, and that to want to save the future you need to both think it is going to be awesome enough to be worth saving, and that we have power to do something constructive. To which he added: Transhumanism also adds diversitythe future does not have to be like the present.

As Manney aptly pointed out, it seems ludicrous to advocate for human enhancement at a time when abortion rights in the U.S. have been rescinded. The rise of anti-vaxxers during the covid-19 epidemic presents yet another complication, showing the extent to which the public willingly rejects a good thing. For me personally, the anti-vaxxer response to the pandemic was exceptionally discouraging, as I often reference vaccines to explain the transhumanist mindsetthat we already embrace interventions that enhance our limited genetic endowments.

Given the current landscape, its my own opinion that self-described transhumanists should advocate and agitate for full bodily, cognitive, and reproductive autonomy, while also championing the merits of scientific discourse. Until these rights are established, it seems a bit premature to laud the benefits of improved memories or radically extended lifespans, as sad as it is to have to admit that.

These contemporary social issues aside, the transhuman future wont wait for us to play catchup. These technologies will arrive, whether they emerge from university labs or corporate workshops. Many of these interventions will be of great benefit to humanity, but others could lead us down some seriously dark paths. Consequently, we must move the conversation forward.

Which reminds me of why I got involved in transhumanism in the first placemy desire to see the safe, sane, and accessible implementation of these transformative technologies. These goals remain worthwhile, regardless of any explicit mention of transhumanism. Thankfully, these conversations are happening, and we can thank the transhumanists for being the instigators, whether you subscribe to our ideas or not.

From the Gizmodo archives:

An Irreverent Guide to Transhumanism and The Singularity

U.S. Spy Agency Predicts a Very Transhuman Future by 2030

Most Americans Fear a Future of Designer Babies and Brain Chips

Transhumanist Tech Is a Boner Pill That Sets Up a Firewall Against Billy Joel

DARPAs New Biotech Division Wants to Create a Transhuman Future

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Navigating the Fourth Turning – International Man

Posted: August 5, 2022 at 2:06 am

These are the times that try mens souls.

So, Thomas Paine wrote in 1775 in his publication of The American Crisis. Not so well-remembered today are the words that followed that famous quote:

Tyranny, like hell, is not easily conquered; yet we have this consolation with us, that the harder the conflict, the more glorious the triumph.

At that time, Colonial America was passing through the early stages of a Fourth Turning, an historical time of crisis that occurs roughly every eighty years.

As a point of reference, a First Turning is a period of renewal; one in which a historical crisis has ended. The populace has risen to the occasion, thrown off tyranny and conquered social, political and economic tribulation. Having done so, they now create a renewal, based on hard work, personal responsibility and moral integrity.

A Second Turning occurs a generation later, when the rewards of a First Turning have resulted in prosperity and stability. Those new adults who have grown up during a First Turning will be well-off and will seek to pursue high-mindedness and social concerns. Along the way, they will also pursue self-indulgence. (A deterioration begins.)

In a Third Turning, again a generation later, complacency sets in. Politically, those individuals who are sociopathic (a clinical aberration, estimated at about 4% of any society at any given time) tend to rise in political spheres, replacing the older generation of responsible people. They tend to raise taxes, increase social welfare programmes and increase government spending in every way really, any excuse to seize increased power over the populace.

Then, in a Fourth Turning, again a generation later, power having been seized, the sociopaths seek total power the elimination of all freedoms, to be replaced by totalitarian rule.

Historically, in a Third Turning, a complacent people make it possible for sociopaths to take power. In a Fourth Turning, the sociopaths exert that power.

It matters little whether the excuses put forward by political leaders are climate control, racial equity, CBDCs, cancel culture, owning nothing, digital IDs, transhumanism, vaccine mandates or a Green New Deal, the objective is singular: total dominance of the ruling class over the subservient class. Any excuse will do, if it has totalitarian rule as its outcome.

In any Fourth Turning, those who are more thoughtful and forward-thinking will begin to make sense of the ruse, but find themselves being heavily criticized by all and sundry. The media will do all within their power to slap down those who denounce the ruling class. But more to the point, the greater proportion of the populace will remain in their slumber and resist the awakening strenuously.

It is at such a time that the few who have figured out the ruse experience their greatest challenge whether to speak out or whether to just go along.

This group must struggle in the darkness to a great degree, as the majority of the population fight against an awakening, as it disturbs their complacency and is too horrendous to contemplate.

The latter half of a Fourth Turning becomes a chaotic and confusing period one in which many people desperately hope to just get along, whilst those who are more visionary become increasingly aware that their freedoms are being flushed away on a wholesale basis.

And, whilst it is the smaller, more visionary group that creates the spark of change, it is, historically, a different and unlikely group that actually creates substantive change in the latter half.

The group that turns the tide is the group that I often (unflatteringly) refer to as the hoi polloi the average guy.

At some point, the average guy, who simply wanted to be allowed to get on with his life go to work, mow the lawn, sit on the couch with a six-pack and watch the game has had his life so disrupted by the ruling sociopaths and their increasingly manic oppression that he accepts that he must turn off the TV and do something.

He is not a leader, but he is a joiner.

When, in Ottawa, Canada, a few truckers staged a small demonstration, and the average guy saw it on the news, he got in his truck and joined. He may have had no real idea of how events might develop; he simply added what weight he had to the effort.

But the very fact that he is the average guy that the bulk of the population is made up of average guys, makes their collective weight greater than those who may have been more inspired thinkers, and more importantly greater than the weight of the oppressors.

As simplistic as a convoy of Canadian truckers may be, their numbers become their strength.

More to the point, they carry with them the sympathies of other average people, who come out to cheer them on, bring them food and donate money.

Not surprisingly, their achievement is brief, as its so simplistic, but they do succeed in bringing about temporary change, setting Government back on its heels.

Then, a few farmers in the Netherlands hear about the Canadians and decside to drive their tractors into the city, and it happens again.

And it keeps happening.

Throughout history, its been the same. In 1775, when Paul Revere rode into Lexington and Concord, its quite unlikely that he shouted courageously, To arms! To arms! That would have been treason and treason was one of only three capital offenses at that time.

More likely, he went to a few back doors and spread the word quietly. After all, the people of America were at that time British. The hoi polloi of the day especially those of middle age or older were relatively successful and had a lot to lose. They did not approve of revolt and were willing to pay the small stamp tax that had triggered it. They argued vociferously in the House of Burgesses to just get along. But a few firebrands kept up their challenge and, eventually, they were joined by farmers and shopkeepers who, like the truckers, had had enough and decided to do something.

For those of us who saw the warning signs early decades ago the first half of the Fourth Turning has been extraordinarily distressing. The Globalists have been thorough in their planning and have successfully executed the removal of freedoms with great stealth that we assumed any thinking person should have seen coming.

But most people are not thinkers. Most people go along. They continue to go along, right until the moment that. they dont.

Thomas Paine was correct. These are the times that try mens souls. Paine was a visionary who, through his writing, attempted to bring about an awakening.

An awakening happens only gradually, but the point arrives when the common man has had about enough. He may not be intellectually inspired, but his collective weight is, and throughout history, has been the turning point.

We are now on that cusp.

Editors Note: Its clear there are some ominous social, political, cultural, and economic trends playing out right now. Many of which seem to point to an unfortunate decline of the West.

Thats precisely why legendary speculator Doug Casey and his team just released this free report, which shows you exactly whats happening and what you can do about it. Click here to download it now.

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Elon Musk and a warning of dystopian future of AI: What is digital and biological computing? – DailyO

Posted: August 5, 2022 at 2:06 am

Elon Musk's tweets are hilarious, market-moving, or lawsuit-enabling comments. Sometimes, they are also interesting and informative. On Wednesday, August 3, 2022, Musk made a statement about digital and biological computing.He said that the former is growing faster than the latter and we need to be tracking the data.

What is he talking about? I had to re-read the tweet twice to understand what he is talking about. After a little bit of research, I discovered another aspect of a futuristic society that we do indeed need to talk about. After a long time, Musk has actually tweeted something that makes sense.

Short answer: AI takeover and the need to merge humans and machines.

Off the bat, it is clear that Musk is talking about artificial intelligence and of course about a subject that is related to one of his companies - Neuralink.

To understand digital and biological computing ratios better, we need to know what Neuralink does.

Neuralink aims to put computer chips in human brains to allow us to complete tasks such as typing, pressing buttons, moving the cursor etc by just thinking about it. In pop culture, you can find references to such technology in Cyborgs - a human and machine hybrid.

So, how are digital and biological computing related? To understand this, let's answer a few questions:

What is digital computing? It is the collective brainpower of a computer, like your mobile phone or laptop or a self-driving car.

What is biological computing? There are two definitions to this. One refers to the collective brainpower of humans. The human brain is still the most sophisticated computer to exist.

Second, it also refers to organic technology that is used for certain medical purposes using human DNA or cells as data. DNA systems are one example of such a technology.

When Musk says that "the ratio of digital to biological compute is growing fast", he is referring to the belief that artificial intelligence is progressing at a faster rate than our natural human brains including the human and machine hybrid technology.

It is not the first time that Musk has spoken about this. He's been quite vocal about the fear that AI will become more powerful than humans in the future.

In 2019, when a Twitter user asked him whether Neuralink was the answer to giving humanity a defence against AI takeover, Musk answered by saying that there are two reasons - long-term and short-term.

He also spoke at length on the subject in 2017 during the launch of Tesla in the UAE. He explained that computers communicate at the speed of "a trillion bits per second", while humans communicate through typing via phones or laptops at 10 bits per second.

Using this explanation, he said that AI can one day become "smarter than the smartest human on earth", a dangerous situation for humanity. The Tesla and SpaceX founder claimed that humans would become slower and irrelevant in a future ruled by artificial intelligence.

An example of this would be human drivers losing their jobs with the advent of driverless cars in the near future.

What's the solution? According to Musk, the solution to avoid a Terminator-like fate of humans is to merge humans with digital intelligence; exactly what his company, Neuralink, wants to do.

There's a term for the theory of cyborgs too - it's called transhumanism. It was first coined in 1957 in an essay.

Do you think that we are progressing a lot slower than our AI counterparts?

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