Healthcare analytics, AI solutions for biological big data, providing an AI platform for the biotech, life sciences, medical and pharmaceutical industries, as well as for related technological approaches, i.e., curation and text analysis with machine learning and other activities related to AI applications to these industries.
2026 Tang Prize in Biopharmaceutical Science Awarded to Three Pioneers of Cellular Immunotherapy Revolutionizing Treatments for Blood Cancers and Solid Tumors
On June 16, the Tang Prize in Biopharmaceutical Science announced its 2026 laureates. The prize, whose laureates from previous cycles have subsequently received Nobel Prize honors, has drawn wide international attention. Three leading scientists in the field of cellular immunotherapy, Drs. Steven A. Rosenberg, Michel Sadelain, and Carl H. June, have been named joint laureates “for the discovery and development of tumor-infiltrating lymphocyte (TIL) and chimeric antigen receptor T-cell (CAR-T) therapies, which have revolutionized treatment for blood cancers and solid tumors.”
Immunosuppression in the Tumor Microenvironment (TME) can lead to exhaustion of T cells, which are responsible for identifying and attacking cancer cells. Cellular immunotherapy uses a patient’s own immune cells, including genetically engineered CAR-T, to recognize and destroy cancer cells, and has emerged as one of the most transformative advances in cancer treatment in recent years. The contributions of the three laureates have laid the foundation for a new era of “living drugs,” turning the patient’s immune system into a powerful medicine with far-reaching impact.
Since the first FDA approval in 2017, CAR-T therapy has already benefited over 30,000 patients with blood cancers worldwide. These therapies provide life-saving options for patients with recurrent and/or refractory blood cancers. Furthermore, TIL therapy has established a new option for treating advanced solid tumors, especially metastatic melanoma. Recent advances in CAR-T therapy in 2026 have also expanded into areas such as CRISPR-Cas9-based cell engineering, treatment of autoimmune diseases such as systemic lupus erythematosus, cardiac injury repair, and research targeting senescence.
Academician Wen-Chang Chang, Chair of the Tang Prize Selection Committee in Biopharmaceutical Science, noted that the Tang Prize in Biopharmaceutical Science recognizes successful drug development, as well as medical and technological research that leads to clinical treatment breakthroughs. In the field of tumor immunology, the inaugural Tang Prize laureates, Drs. James P. Allison and Tasuku Honjo, respectively identified CTLA-4 and PD-1 as key inhibitory immune checkpoints, paving the way for the development of antibody drugs known as immune checkpoint inhibitors and bringing major advances to the treatment of many cancers, particularly certain solid tumors. This year’s three laureates specialize in cellular immunotherapy. From Dr. Rosenberg’s pioneering clinical work with TILs, to the foundational advances by Dr. Sadelain and Dr. June that brought CAR-T therapy toward maturity and clinical application, the three scientists helped turn the human immune system into a powerful anti-cancer medicine, creating breakthrough treatments for malignant blood diseases such as leukemia, lymphoma, and multiple myeloma.
The pioneering work in this field was fundamentally established by Dr. Steven A. Rosenberg, widely known as the “Father of Cancer Immunotherapy.” As Chief of the Surgery Branch at the National Cancer Institute (NCI) since 1974, he has built the foundational clinical framework for adoptive cell therapy (ACT) 1. In the 1980s, Dr. Rosenberg showed that high-dose interleukin-2 (IL-2) could stimulate T cell proliferation and enhance their ability to kill cancer cells, leading to regression of metastatic tumors — the first clinical proof of T cells’ anti-cancer potential, leading to the FDA approval of IL-2 as the first cancer immunotherapy agent. He also demonstrated that TILs could induce regression of metastatic melanoma. In the 1990s, he achieved another milestone by receiving the first regulatory approval to introduce foreign genes into humans3.
Dr. Rosenberg has pioneered the development of effective immunotherapies for patients with advanced cancer. His studies of cell transfer immunotherapy using tumor infiltrating lymphocytes (TIL) have resulted in durable complete remissions in patients with advanced solid cancers. He has also pioneered the development of gene therapy and was the first to successfully insert foreign genes into humans. His recent studies of the adoptive transfer of genetically modified lymphocytes using chimeric antigen receptors (CAR) or conventional T-cell receptors (TCR) have resulted in the regression of metastatic cancer in patients with lymphomas and solid cancers. His current research is aimed at defining the host immune response of patients to their cancers. These studies emphasize the ability of human lymphocytes to recognize unique cancer antigens and the identification of anti-tumor T-cell receptors that can be exploited to develop new cell transfer immunotherapies. As Chief, Dr. Rosenberg also oversees the Branch’s extensive clinical program aimed at translating scientific advances into effective immunotherapies for patients with advanced cancers arising from the breast, gastrointestinal tract, and pancreas.
Please Watch VIDEO
Dr. Michel Sadelain and Dr. Carl H. June are two leading pioneers in the development of CAR-T cell therapy. In the early development of antigen receptor engineering, research teams incorporated the intracellular CD3ζ chain4— responsible for transmitting activation signals — which Dr Sadelain found to be ineffective on its own. He discovered that integrating an additional CD28 co-stimulatory domain2 directly into the receptor yielded T cells with therapeutic potential, thereby establishing the core architecture that has become standard framework for all subsequently FDA-approved CAR-T therapies. In addition, Dr. Sadelain identified a molecule named CD19 as a potential target for treating B cell malignancies, which include leukemias and lymphomas, and provided the first demonstration that human CD19 CAR T cells could treat cancer in mice. In 2013, his team at Memorial Sloan Kettering Cancer Center (MSKCC) reported the first significant therapeutic responses to CD19 CAR-T cells in adults with relapsed and refractory acute lymphoblastic leukemia (ALL).
Dr. June made the key breakthroughs that carried CAR-T therapy toward clinical success. He helped demonstrate that CD28 co-stimulation2 as essential for T-cell activation and applied the anti-CD3 and anti-CD28 bead expansion protocol, which has become the global manufacturing standard for CAR-T cells. He also engineered CAR constructs incorporating the 4-1BB (CD137) co-stimulatory domain and the T-cell receptor-zeta chain (TCR-ζ) to enhance the proliferation and long-term survival of transferred T cells, while also addressing the challenges of large-scale manufacturing. Dr. June then led the first successful clinical trials of CD19-targeted CAR-T cells, achieving durable remissions in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). His partnership with Novartis culminated in Kymriah becoming the first FDA-approved CAR-T therapy in 2017, marking a major step in bringing CAR-T therapy from research into clinical medicine.
Among the many patients who have benefited from CAR-T therapy, the story of Emily Whitehead is especially compelling. She was the first pediatric patient to receive CAR-T therapy. Diagnosed with ALL at just 5 years old in 2010, she underwent more than 16 months of chemotherapy without success before receiving CAR-T therapy in 2012. After treatment, her cancer went into complete remission, and she has remained healthy for 14 years. Over the years, Emily has continued to share her story publicly, advocating and raising funds for leukemia patients every year. Her recovery has moved and inspired countless patients and families.
Please Watch VIDEO on Dr. June
Footnotes:
Adoptive cell transfer (ACT) is a form of immunotherapy in which a patient’s own immune cells are collected, expanded or modified outside the body, and then reinfused into the patient to attack cancer.
CD28 is a co-stimulatory receptor on T cells that provides a crucial “second signal” for T-cell activation, proliferation, and survival.
Because gene-transfer research raises ethical and safety concerns, it had long been subject to strict regulation. The 1990 approval laid an important foundation for later genetically modified immune cell therapies.
The CD3ζ chain is an intracellular signaling chain in T cells that helps initiate T-cell activation and immune-killing responses.
About the Tang Prize
Since the advent of globalization, humanity has enjoyed unprecedented benefits from advances in civilization and science. Yet a multitude of challenges, such as climate change, the emergence of new infectious diseases, the widening wealth gap, and moral degradation, have surfaced along the way. Against this backdrop, Dr. Samuel Yin established the Tang Prize in December 2012. It consists of four award categories: Sustainable Development, Biopharmaceutical Science, Sinology, and Rule of Law. Every two years, four independent and professional selection committees, comprising many internationally renowned experts, scholars, and Nobel laureates, choose Tang Prize laureates who have made substantive contributions and generated a far-reaching impact on the world, regardless of race, nationality, gender, or religion. A cash prize of NT$50 million (approximately US$1.6 million) is allocated to each category, with NT$10 million (approximately US$320,000) of it being a grant intended for research or educational outreach programs to encourage professionals in every field to examine mankind’s most urgent needs in the 21st century, and become leading forces in the sustainable development of human society through their outstanding research outcomes and active civic engagement.
For more articles on Tumor Infiltrating Lymphocytes and CAR-T Therapy on this Open Access Scientific Journal please see:
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class X: +300 Audio Podcasts Library: Interviews with Scientific Leaders
Curator: Aviva Lev-Ari, PhD, RN
We had researched the topic of AI Initiatives in Big Pharma in the following article:
Authentic Relevance of LPBI Group’s Portfolio of IP as Proprietary Training Data Corpus for AI Initiatives at Big Pharma
We are publishing a Series of Five articles that demonstrate the Authentic Relevance of Five of the Ten Digital IP Asset Classes in LPBI Group’s Portfolio of IP for AI Initiatives at Big Pharma.
For the Ten IP Asset Classes in LPBI Group’s Portfolio, See
This Corpus comprises of Live Repository of Domain Knowledge Expert-Written Clinical Interpretationsof Scientific Findings codified in the following five Digital IP ASSETS CLASSES:
• IP Asset Class V: 7,500 Biological Images in our Digital Art Media Gallery, as prior art. The Media Gallery resides in WordPress.com Cloud of LPBI Group’s Web site
BECAUSE THE ABOVE ASSETS ARE DIGITAL ASSETS they are ready for use as Proprietary TRAINING DATA and INFERENCE for AI Foundation Models in HealthCare.
Expert‑curated healthcare corpus mapped to a living ontology, already packaged for immediate model ingestion and suitable for safe pre-training, evals, fine‑tuning and inference. If healthcare domain data is on your roadmap, this is a rare, defensible asset.
The article TITLE of each of the five Digital IP Asset Classes matched to AI Initiatives in Big Pharma, an article per IP Asset Class are:
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class I: PharmaceuticalIntelligence.com Journal, 2.5MM Views, 6,250 Scientific articles and Live Ontology
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class II: 48 e-Books: English Edition & Spanish Edition. 152,000 pages downloaded under pay-per-view
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class III: 100 e-Proceedings and 50 Tweet Collections of Top Biotech and Medical Global Conferences, 2013-2025
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class V: 7,500 Biological Images in LPBI Group’s Digital Art Media Gallery, as prior art
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class X: +300 Audio Podcasts Library: Interviews with Scientific Leaders
LPBI Group’s IP Asset Class X: A Library of Podcasts are a “live repository” primed for Big Pharma AI, fueling from R&D reviews to global equity. Technical Implications: Enables auditory-multimodal models for diagnostics/education. Business Implications: Accelerates $500M ROI; licensing for partnerships. Unique Insight: As unscripted leader interviews, they provide a “verbal moat” in AI—completing series’ holistic pharma data ecosystem.Promotional with links to podcast library/IP portfolio. Synthesizes series by emphasizing auditory human-AI synergy.
In the series of five articles, as above, we are presenting the key AI Initiatives in Big Pharma as it was created by our prompt to @Grok on 11/18/2025:
Generative AI tools that save scientists up to 16,000 hours annually in literature searches and data analysis.
Drug Discovery and Development Acceleration Pfizer uses AI, supercomputing, and ML to streamline R&D timelines
Clinical Trials and Regulatory Efficiency AI:
-Predictive Regulatory Tools
-Decentralize Trials
-inventory management
Disease Detection and Diagnostics:
– ATTR-CM Initiative
– Rare diseases
Generative AI and Operational Tools:
– Charlie Platform
– Scientific Data Cloud AWS powered ML on centralized data
– Amazon’s SageMaker /Bedrock for Manufacturing efficiency
– Global Health Grants:
Pfizer Foundation’s AI Learning Lab for equitable access to care and tools for community care
Partnerships and Education
– Collaborations: IMI Big Picture for 3M – sample disease database
– AI in Pharma AIPM Symposium: Drug discovery and Precision Medicine
– Webinars of AI for biomedical data integration
– Webinar on AI in Manufacturing
Strategic Focus:
– $500M R&D reinvestment by 2026 targets AI for Productivity
– Part of $7.7B cost savings
– Ethical AI, diverse DBs
– Global biotech advances: China’s AI in CRISPR
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class X: +300 Audio Podcasts Library: Interviews with Scientific Leaders
AI Initiatives in Big Pharma @Grok prompt & Proprietary Training Data and Inference by LPBI Group’s IP Asset Class X: +300 Audio Podcasts Library: Interviews with Scientific Leaders
Overview: Final (fifth) in LPBI Group’s five-article series on AI-ready digital IP assets for pharma. This installment highlights IP Asset Class X—+300 audio podcasts of interviews with scientific leaders—as a proprietary, expert-curated auditory corpus for training and inference in healthcare AI models. Using a November 18, 2025, Grok prompt on Pfizer’s AI efforts, it maps the library to pharma applications, emphasizing audio ingestion for breakthroughs review, education, and platform integration. Unlike visual/text prior classes, this focuses on verbal expert insights for multimodal/hybrid AI, positioning them as a “rare, defensible” resource for ethical, diverse foundation models.Main Thesis and Key Arguments
Core Idea: LPBI’s +300 podcasts capture unscripted scientific discourse from leaders, forming a live repository of domain knowledge ideal for AI ingestion—enhancing Big Pharma’s shift from generic to human-curated models for R&D acceleration and equitable care.
Value Proposition: Part of ten IP classes (five AI-ready: I, II, III, V, X); podcasts equivalent to $50MM value in series benchmarks, with living ontology for semantic mapping. Unique for hybrid uses (e.g., education starters) and safe pre-training/fine-tuning, contrasting open-source data with proprietary, ethical inputs.
Broader Context: Caps series by adding auditory depth to text/visual assets; supports Pfizer’s $500M AI reinvestment via productivity gains (e.g., 16,000 hours saved).
AI Initiatives in Big Pharma (Focus on Pfizer) Reuses Grok prompt highlights, presented in an integrated mapping table (verbatim):
AI Initiative at Big Pharma i.e., Pfizer
Description
Generative AI tools
Save scientists up to 16,000 hours annually in literature searches and data analysis.
Drug Discovery and Development Acceleration
Pfizer uses AI, supercomputing, and ML to streamline R&D timelines.
Charlie Platform; Scientific Data Cloud AWS powered ML on centralized data; Amazon’s SageMaker/Bedrock for Manufacturing efficiency; Global Health Grants: Pfizer Foundation’s AI Learning Lab for equitable access to care and tools for community care.
Partnerships and Education
Collaborations: IMI Big Picture for 3M-sample disease database; AI in Pharma AIPM Symposium: Drug discovery and Precision Medicine; Webinars of AI for biomedical data integration; Webinar on AI in Manufacturing.
Strategic Focus
$500M R&D reinvestment by 2026 targets AI for Productivity; Part of $7.7B cost savings; Ethical AI, diverse DBs; Global biotech advances: China’s AI in CRISPR.
Mapping to LPBI’s Proprietary DataCore alignment table (verbatim extraction, linking Pfizer initiatives to Class X podcasts):
AI Initiative at Big Pharma i.e., Pfizer
Library of Audio and Video Podcasts N = +300
Generative AI tools (16,000 hours saved)
(No specific mapping provided.)
Drug Discovery and Development Acceleration
Review ALL SCIENTIFIC BREAKTHROUGHS.
Clinical Trials and Regulatory Efficiency
(No specific mapping provided.)
Disease Detection and Diagnostics (ATTR-CM, rare diseases)
(No specific mapping provided.)
Generative AI and Operational Tools (Charlie, AWS, etc.)
Ingest to Charlie Platform all +300 Podcasts.
Partnerships and Education (IMI, AIPM, webinars)
Use Podcast for Education; Use Podcast as Hybrid: Start presentation with a Podcast continue with a life interview.
Strategic Focus ($500M reinvestment, ethics)
(No specific mapping provided.)
Methodologies and Frameworks
AI Training Pipeline: Ingest audio into Charlie/AWS for pre-training (expert discourse corpus), fine-tuning (e.g., breakthrough reviews), and inference (e.g., educational hybrids). Use ontology for thematic mapping; Grok prompt for sourcing initiatives.
Productivity Model: Boosts Pfizer’s $7.7B savings via auditory data for diverse, ethical AI (e.g., Learning Lab grants); hybrid formats for webinars/symposia.
Insights: Quote from Dr. Stephen J. Williams, PhD: Assets as “codified digital treasures” for safe healthcare AI. Predicts revolution in verbal inference for precision medicine.
Conclusions and Implications
LPBI Group’s IP Asset Class X:
A Library of Podcasts are a “live repository” primed for Big Pharma AI, fueling from R&D reviews to global equity. Technical Implications: Enables auditory-multimodal models for diagnostics/education. Business Implications: Accelerates $500M ROI; licensing for partnerships. Unique Insight: As unscripted leader interviews, they provide a “verbal moat” in AI—completing series’ holistic pharma data ecosystem.Promotional with links to podcast library/IP portfolio. Synthesizes series by emphasizing auditory human-AI synergy.
@Grok was prompted to summarize the Table of Contents of the e-Book that present the Library of Podcast INDEX.
Overview of IP Asset Class X: +300 Audio Podcasts – Interviews with Scientific LeadersThe BioMed Audio Podcast Library from LPBI Group is a valuable intellectual property asset in the biomedical field, featuring over 301 audio podcasts created from interviews, curations, and discussions with prominent scientific leaders. This collection highlights breakthroughs in areas like genomics, cancer research, immunology, precision medicine, and public health policy. Curated by experts such as Aviva Lev-Ari, PhD, RN (197 podcasts), Larry H. Bernstein, MD, FCAP (48 podcasts), and Stephen J. Williams, PhD (38 podcasts), the library is organized into 21 thematic chapters for easy navigation.Key features include:
Search and Accessibility: Filter by chapter, curator, subject, or podcast ID. Each entry includes text-to-speech conversion and NLP-generated WordClouds for topic visualization.
Content Focus: Emphasizes Nobel laureates, key opinion leaders, and innovators discussing technologies like CRISPR-Cas9, mRNA vaccines, immunotherapy, and biotechnology ventures.
Format and Updates: Derived from articles on real-time events (e.g., COVID-19 impacts, award announcements). The library continues to expand, with no direct audio embeds—access via linked articles for full transcripts and playback.
Themes Covered: Public health policy, cardiovascular science, neuroscience, academic institutions, and more, with a strong emphasis on translational research and personalized medicine.
This asset represents a rich repository for researchers, students, and professionals seeking insights from leaders like Francis Collins, Jennifer Doudna, and Siddhartha Mukherjee.Selected Highlights by ChapterBelow are curated examples from key chapters, showcasing interviews with scientific leaders. For the full library (301+ entries), visit the source page.
Chapter 1: Public Health
Podcast ID
Curator
Title
Scientific Leader(s)
Brief Description
Link
17
Aviva Lev-Ari
LEADERS in Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment: Part 2
Leaders in genome sequencing
Explores genetic mutations’ role in personalized cancer therapies.
This selection captures the library’s depth, blending historical perspectives (e.g., Watson) with cutting-edge topics (e.g., CRISPR, immunotherapy). For deeper dives, use the site’s search tools to explore chapters like Cardiovascular Science (36 podcasts) or Immunology.
Paul G. Yock, Recipient of the 2024 National Medal of Technology and Innovation, Professor of Cardiovascular Medicine at Stanford Medical School
Curator: Aviva Lev-Ari, PhD, RN
NMTI Citation
Paul G. Yock, Stanford University
For innovations in interventional cardiology. Paul Yock’s visionary work understanding the human heart is applied around the world today to improve patient care and save countless lives. His creation of the Biodesign approach to training future leaders of biotechnology and health care ensures his insights and experience will benefit generations to come.
Recipients of the 2024 National Medal of Technology and Innovation, administered by President Joe Biden and Laureates of the National Medal of Science, administered by NSF
Paul Yock – The Martha Meier Weiland Professor in the School of Medicine and Professor of Bioengineering, Cardiovascular Medicine, and (by courtesy) of Mechanical Engineering
Scientific Leadership Council Member, Clark Center Faculty
Dr. Paul Yock is the Martha Meier Weiland Professor of Medicine and founding co-chair of Stanford’s Department of Bioengineering, with courtesy appointments in the Graduate School of Business and the Department of Mechanical Engineering. He is also founder and director of the Stanford Byers Center for Biodesign.
After completing his undergraduate and graduate studies at Amherst College and Oxford, respectively, Paul received his MD from Harvard Medical School followed by internship and residency training at the University of California, San Francisco and a fellowship in cardiology at Stanford. He began his faculty career as an interventional cardiologist at UCSF and then moved to Stanford in 1994.
Paul has authored over 300 peer-reviewed publications, chapters and editorials, two textbooks, and over 50 US patents. He is internationally known for his work in inventing, developing, and testing new devices, including the Rapid Exchange™ stenting and balloon angioplasty system, which is now the primary system in use worldwide. He also invented the fundamental approach to intravascular ultrasound imaging and founded Cardiovascular Imaging Systems (CVIS), later acquired by Boston Scientific. Recent awards include the Transcatheter Therapeutics (TCT) Career Achievement Award, the American College of Cardiology Distinguished Scientist Award, and the National Academy of Engineering’s 2018 Bernard M. Gordon Prize for Innovation in Engineering and Technology Education.
Bio
Yock began his faculty career as an interventional cardiologist at UC San Francisco and then moved to Stanford in 1994. Yock is known for his work in inventing, developing and testing new devices, including the
Rapid Exchange angioplasty and stenting system, which is the primary approach used worldwide. Yock also authored the fundamental patents for
intravascular ultrasound imaging, conducted the initial clinical trials and
established the Stanford Center for Research in Cardiovascular Interventions as a core laboratory for analysis of intravascular ultrasound clinical studies. He also
invented the Smart Needle and
is a co-inventor of the strain-reduction patch for wound healing.
Yock was founding Co-Chair of the Department of Bioengineering and continues research related to new device technologies.
Yock also was the founding director of the Stanford Byers Center for Biodesign – dedicated to advanced training in medical technology innovation.
Abstract: A catheter is provided for insertion in the he blood vessel of a patient for ultrasonically imaging the vessel wall. The catheter includes a tubular element and an internally housed drive cable for effective circumferential scan about the catheter of an ultrasonic generating means. Both the tubular element and the drive cable are of a size and flexibility sufficient to permit their introduction into the vessel and subsequent advancement through the vessel to the location of the vessel wall where imaging is desired.
Abstract: Devices and methods for obtaining a three-dimensional image of an internal body site are provided. The subject devices are elongated structures (e.g., catheters) having a plurality of ultrasonic transducers located at their distal end. The configuration of the plurality of ultrasonic transducers may be reversibly changed from a first to a second configuration, where the radial aperture of the plurality of ultrasonic transducers is greater in the second configuration than in the first configuration. A feature of certain embodiments of the subject invention is that the plurality of ultrasonic tranducers are configured in the second configuration as a substantially continuous set of transducers. In using the subject imaging devices, the distal end of the devices is positioned at the internal body site of interest while the plurality of ultrasonic transducers is in the first configuration.
Type: Application
Filed: November 10, 2004
Publication date: September 29, 2005
Inventors: Richard Popp, Ali Hassan, Christian Eversull, Jeremy Johnson, Paul Yock
Abstract: Apparatus for introduction into the vessel of a patient comprising a guiding catheter adapted to be inserted into the vessel of the patient and a device adapted to be inserted into the guiding catheter. The device includes a flexible elongate member and a sleeve carried by the flexible elongate member near the distal extremity thereof and extending from a region near the distal extremity to a region spaced from the distal extremity of the flexible elongate element. The device also includes a guide wire adapted to extend through the sleeve so that the guide wire extends rearwardly of the sleeve extending alongside of and exteriorally of the flexible elongate element into a region near the proximal extremity of the flexible elongate element.
Abstract: A catheter system for localized or semi-localized administration of agents through the wall of a blood vessel is provided. Various catheter system constructions which use at least one expandable occluding device to create an isolated region are provided. Constructions using one catheter and one occlusion device are provided, along with constructions using two catheters and multiple occlusion devices. The catheter system may include a catheter with a variable stiffness along its length. The catheter system may also include a guide wire integrated with an inner catheter. The catheter can infuse the agent into the blood vessel in a pressure regulated manner. Methods for delivery and infusion of the agent within a blood vessel are also provided.
Type: Application
Filed: February 20, 2004
Publication date: March 17, 2005
Inventors: Michi Garrison, Todd Brinton, Peter Campbell, Steve Roe, Stephen Salmon, Paul Yock
Abstract: Apparatus and method are described for introducing an imaging catheter to the coronary vasculature. A guiding catheter is introduced so that the distal end of the guiding catheter engages a coronary os. The distal end of the guiding catheter is shaped so that a mark on the distal end is oriented in a predetermined orientation relative to the coronary vasculature. An imaging catheter is then introduced through the guiding catheter and an image of the mark is produced with the imaging catheter while in the guiding catheter. In this manner, the relative orientation of the produced image and the coronary vasculature is known.
Type: Grant
Filed: October 20, 1997
Date of Patent: March 9, 1999
Assignee: Cardiovascular Imaging Systems, Inc.
Inventors: Paul Yock, Yue-Teh Jang, Stephen M. Salmon
Abstract: Apparatus and method are described for introducing an imaging catheter to the coronary vasculature. A guiding catheter is introduced so that the distal end of the guiding catheter engages a coronary os. The distal end of the guiding catheter is shaped so that a mark on the distal end is oriented in a predetermined orientation relative to the coronary vasculature. An imaging catheter is then introduced through the guiding catheter and an image of the mark is produced with the imaging catheter while in the guiding catheter. In this manner, the relative orientation of the produced image and the coronary vasculature is known.
Type: Grant
Filed: September 4, 1996
Date of Patent: March 10, 1998
Assignee: Cardiovascular Imaging Systems Inc.
Inventors: Paul Yock, Yue-Teh Jang, Stephen M. Salmon
Abstract: Apparatus and method are described for introducing an imaging catheter to the coronary vasculature. A guiding catheter is introduced so that the distal end of the guiding catheter engages a coronary os. The distal end of the guiding catheter is shaped so that a mark on the distal end is oriented in a predetermined orientation relative to the coronary vasculature. An imaging catheter is then introduced through the guiding catheter and an image of the mark is produced with the imaging catheter while in the guiding catheter. In this manner, the relative orientation of the produced image and the coronary vasculature is known.
Type: Grant
Filed: June 6, 1995
Date of Patent: January 28, 1997
Inventors: Paul Yock, Yue-Teh Jang, Stephen M. Salmon
AACR 2023 Meeting Highlights: Reports from Plenary Sessions and Major Symposium Talks
Reporter: Stephen J. Williams, Ph.D.
Highlights from Sunday April 16,2023
Nobel Laureate will discuss her work investigating the glycobiology of cancer
Carolyn R. Bertozzi, PhD, shared the Nobel Prize in Chemistry in 2022 for her invention of bioorthogonal chemistry, which is a class of chemical reactions that are compatible with living systems. These chemistries allow researchers to explore molecular imaging and drug targeting without interfering with natural biological processes. Bertozzi’s AACR Award for Outstanding Achievement in Chemistry in Cancer Research, and her lecture, focus on the glycobiology of cancer.
Carolyn R. Bertozzi, PhD
“There is a family of receptors on immune cells that bind carbohydrates,” said Bertozzi, Baker Family Director of the Sarafan ChEM-H Institute and Anne T. and Robert M. Bass Professor of Chemistry at Stanford University. “Called the ‘sialic acid-binding immunoglobulin-like lectins’ — abbreviated Siglecs — these receptors bind carbohydrates that possess the sugar sialic acid. There are 14 Siglec family members in humans and they are found in various combinations on every type of immune cell — T cells, macrophages, neutrophils, NK cells, all of the immune cell types that are important in anti-cancer immunity. As tumors progress, they often overexpress sialoglycan ligands for Siglecs, which allows them to engage these receptors and suppress immune-cell reactivity. We have focused on developing immune therapies that disrupt Siglec-ligand interactions.”
Bertozzi will discuss this area of her research during her award lecture, Targeting the Glycocalyx for Cancer Immune Therapy, at 4:30 p.m. ET Sunday in Tangerine Ballroom 3-4 (WF3-4) at the convention center.
“The signaling biochemistry of the Siglec family of checkpoint receptors is similar to the signaling biochemistry that PD-1 participates in,” Bertozzi explained. “They are like PD-1 except that they bind sugars rather than proteins, and they are present on every type of immune cell, including activated T cells, but also myeloid-derived cell types.”
“Glycobiology is an important area to become more familiar with if you want to truly be able to move the needle,” she said. “The science we have uncovered has led to the identification of exciting new targets, which has enabled us to invent new therapeutic modalities.”
Familiar small molecules and antibodies are of marginal use in targeting sugars, Bertozzi explained. Because carbohydrates are different types of molecules than traditional cancer targets, they need nontraditional mechanisms of action.A new class of targeted enzymes can edit the cell surface glycocalyx (or sugar coating) and deprive cancers of their ability to engage Siglec receptors. Without the broad inhibitory activity of Siglecs, the immune system remains free to engage and, hopefully, destroy tumors. At least one investigative agent is in phase I human trials and is poised to move into phase II.
“Glycobiology might explain why so many patients don’t respond to anti-PD-1 and anti-PD-L1 antibodies,” Bertozzi said. “We think a large fraction of tumors suppress the immune response through Siglec engagement.”
Other Articles on Real Time Coverage of AACR Meetings on this Open Access Scientific Journal Include:
Named for ACGT co-founder, Edward Netter, the award recognizes a researcher who has made unparalleled and groundbreaking contributions to the field of cell and gene therapy for cancer. Dr. Mackall is a leader in advancing cell and gene therapies for the treatment of solid tumors, with a major focus on children’s cancers.
In addition to being an ACGT research fellow and a member of ACGT’s Scientific Advisory Council, Dr. Mackall is the Ernest and Amelia Gallo Family professor of Pediatrics and Medicine at Stanford University, the founding director of the Stanford Center for Cancer Cell Therapy, associate director of the Stanford Cancer Institute, leader of the Cancer Immunotherapy Program and director of the Parker Institute for Cancer Immunotherapy. She has led numerous groundbreaking clinical trials to treat children with sarcomas and brain cancers.
“There is exciting progress happening in the field of cancer cell and gene therapy,” said Kevin Honeycutt, CEO and president of ACGT. “We continue to see the FDA approve cell and gene therapy treatments for blood cancers, while research for solid tumors is now progressing to clinical trials. These successes are linked to the funding of ACGT, and Dr. Crystal Mackall is one of the best examples of a researcher who refused to accept the status-quo of standard cancer treatment and committed to developing novel cell and gene therapies for children with difficult-to-treat tumors. ACGT is proud that Dr. Mackall is an ACGT Research Fellow, a member of ACGT’s Scientific Advisory Council, and the newest recipient of the Edward Netter Leadership Award.”
The ACGT Awards Luncheon will celebrate the non-profit organization’s 20th anniversary and usher in a new decade as the only nonprofit dedicated exclusively to funding cancer cell and gene therapy research. ACGT funds innovative scientists and biotechnology companies working to harness the power of cell and gene therapy to transform how cancer is treated and to drive momentum toward a cure.
The Edward Netter Leadership Award will be presented to Dr. Mackall by Carl June, MD, of the University of Pennsylvania, who received the honor at ACGT’s 2019 Awards Gala. ACGT grant funding enabled Dr. June to research and develop cell and gene therapies that led to the first FDA approvals of CAR T-cell therapies for cancer.
For more than 20 years, Alliance for Cancer Gene Therapy has funded research that is bringing innovative treatment options to people living with deadly cancers – treatments that save lives and offer new hope to all cancer patients. Alliance for Cancer Gene Therapy funds researchers who are pioneering the potential of cancer cell and gene therapy – talented visionaries whose scientific advancements are driving the development of groundbreaking treatments for ovarian, prostate, sarcoma, glioblastoma, melanoma and pancreatic cancers. One hundred percent of all public funds raised by Alliance for Cancer Gene Therapy directly support research and programs. For more information, visit acgtfoundation.org, call (203) 358-5055, or join the Alliance for Cancer Gene Therapy community on Facebook, Twitter, LinkedIn, Instagram and YouTube @acgtfoundation.
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Other Related Articles in this Open Access Scientific Journal Include
Joe Biden Announced Science Team Nominations for the New Administration
Reporter: Stephen J. Williams, PhD
Article ID #287: Joe Biden Announced Science Team Nominations for the New Administration. Published on 1/17/2021
WordCloud Image Produced by Adam Tubman
In an announcement televised on C-Span, President Elect Joseph Biden announced his new Science Team to advise on science policy matters, as part of the White House Advisory Committee on Science and Technology. Below is a video clip and the transcript, also available at
Genetic scissors: a tool for rewriting the code of life
Emmanuelle Charpentier and Jennifer A. Doudna have discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.
Researchers need to modify genes in cells if they are to find out about life’s inner workings. This used to be time-consuming, difficult and sometimes impossible work. Using the CRISPR/Cas9 genetic scissors, it is now possible to change the code of life over the course of a few weeks.
“There is enormous power in this genetic tool, which affects us all. It has not only revolutionised basic science, but also resulted in innovative crops and will lead to ground-breaking new medical treatments,” says Claes Gustafsson, chair of the Nobel Committee for Chemistry.
As so often in science, the discovery of these genetic scissors was unexpected. During Emmanuelle Charpentier’s studies of Streptococcus pyogenes, one of the bacteria that cause the most harm to humanity, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.
Charpentier published her discovery in 2011. The same year, she initiated a collaboration with Jennifer Doudna, an experienced biochemist with vast knowledge of RNA. Together, they succeeded in recreating the bacteria’s genetic scissors in a test tube and simplifying the scissors’ molecular components so they were easier to use.
In an epoch-making experiment, they then reprogrammed the genetic scissors. In their natural form, the scissors recognise DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life.
Since Charpentier and Doudna discovered the CRISPR/Cas9 genetic scissors in 2012 their use has exploded. This tool has contributed to many important discoveries in basic research, and plant researchers have been able to develop crops that withstand mould, pests and drought. In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true. These genetic scissors have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind.
Emmanuelle Charpentier, born 1968 in Juvisy-sur-Orge, France. Ph.D. 1995 from Institut Pasteur, Paris, France. Director of the Max Planck Unit for the Science of Pathogens, Berlin, Germany.
Jennifer A. Doudna, born 1964 in Washington, D.C, USA. Ph.D. 1989 from Harvard Medical School, Boston, USA. Professor at the University of California, Berkeley, USA and Investigator, Howard Hughes Medical Institute.
Other Articles on the Nobel Prize in this Open Access Journal Include:
Article ID #274: My Memories Tell a Story to Share by Larry Howard Bernstein, MD, FCAP. Published 4/19/2020
WordCloud Image Produced by Adam Tubman
Updated on 6/2/2020
In preparation for a PODCAST with Dr. Larry, we prepared the following content:
For many years, he was the Chief Scientific Officer and Member of the Board of Leaders in Pharmaceutical Business Intelligence (LPBI) Group, a Pharmaceutical Media Venture with several Cloud Based products: (1) an Open Access Online Scientific Journal
PharmaceuticalIntelligence.com, (2) a BioMed e-Series of 16 volumes in Medicine (3) A Real Time Press Coverage of Biotech and Medical Conferences (4) a Podcast Library of Interviews with Key Opinion Leaders (4) A Platform with Composition of Methods and (5) a Team of Experts, Authors, Writers.
Dr. Bernstein had contributed 1,400 curated articles to LPBI’s Journal, mentioned above and served as Editor and Content Consultant to each of the 16 volumes in LPBI’s BioMed e-Series.
Examples of the TOP articles in the Journal by e-Readers Views shows the cardinal positioning of Dr. Bernstein’s publications.
Top Posts for all days ending 2020-06-02 (Summarized)
Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?
17,117
Larry H. Bernstein, MD, FACP
Investigator Initiated Research
Recent comprehensive review on the role of ultrasound in breast cancer management
14,242
Dr. D. Nir
Commission by Aviva Lev-Ari, PhD, RN
Do Novel Anticoagulants Affect the PT/INR? The Cases of XARELTO (rivaroxaban) and PRADAXA (dabigatran)
13,839
Dr. Pearlman, MD, PhD, FACC & Aviva Lev-Ari, PhD, RN
Commission by Aviva Lev-Ari, PhD, RN
Paclitaxel vs Abraxane (albumin-bound paclitaxel)
13,709
Tilda Barliya, PhD
Investigator Initiated Research
Apixaban (Eliquis): Mechanism of Action, Drug Comparison and Additional Indications
8,230
Aviva Lev-Ari, PhD, RN
Investigator Initiated Research
Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care
7,903
Dr. Pearlman, MD, PhD, FACC & Aviva Lev-Ari, PhD, RN
Investigator Initiated Research
Mesothelin: An early detection biomarker for cancer (By Jack Andraka)
6,540
Tilda Barliya, PhD
Investigator Initiated Research
Our TEAM
6,505
Internet Access
Tabulation
Biochemistry of the Coagulation Cascade and Platelet Aggregation: Nitric Oxide: Platelets, Circulatory Disorders, and Coagulation Effects
5,221
Larry H. Bernstein, MD, FACP
Investigator Initiated Research
Interaction of enzymes and hormones
4,901
Larry H. Bernstein, MD, FACP
Commission by Aviva Lev-Ari, PhD, RN
Akt inhibition for cancer treatment, where do we stand today?
4,852
Ziv Raviv, PhD
Investigator Initiated Research
AstraZeneca’s WEE1 protein inhibitor AZD1775 Shows Success Against Tumors with a SETD2 mutation
4,535
Stephen J. Williams, PhD
Investigator Initiated Research
The History and Creators of Total Parenteral Nutrition
4,511
Larry H. Bernstein, MD, FACP
Commission by Aviva Lev-Ari, PhD, RN
Newer Treatments for Depression: Monoamine, Neurotrophic Factor & Pharmacokinetic Hypotheses
4,365
Zohi Sternberg, PhD
Investigator Initiated Research
FDA Guidelines For Developmental and Reproductive Toxicology (DART) Studies for Small Molecules
4,188
Stephen J. Williams, PhD
Investigator Initiated Research
The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia, Similarities and Differences, and Pharmaceutical Targets
4,038
Dr. Pearlman, MD, PhD, FACC, Larry H. Bernstein, MD, FACP & Aviva Lev-Ari, PhD, RN
Commission by Aviva Lev-Ari, PhD, RN
Founder
3,895
Aviva Lev-Ari, PhD, RN
Investigator Initiated Research
That small sample from a universe of 1,400 articles reflects just a glimpse of the topics that he had covered in his writing.
In addition, in 2020 the Journal ontology has 700 Categories of Research, more than 50% were create by Dr. Bernstein for allowing a precise classification of the wide range of topics his life body of research had covered, chiefly: Cancer, Genomics, Pathology, Coagulation, Cardiovascular, Nutrition, Cell Biology and Biochemistry Processes, at large.
Dr. Bernstein served on the Board of Director of NAACLS and the American Library Association Commission on Accreditation and he is listed in the America’s Top Physicians.
He has three patents:
1. Measuring Lactate Dehydrogenase Isoenzymes by differential inhibition of heart and muscle enzymes using the inhibition by a triplex formed by pyruvate – NAD+ and LDH.
2. Measuring the mitochondrial Malate Dehydrogenase using the inhibition of mMDH by a triplex formed by OAA – NAD+ – and mMDH in the laboratory of Nathan Oren Kaplan (NAS).
3. Measuring a cancer modified MDH by loss of mMDH inhibition with Prof. Johannes Everse. In addition, only a provisional patent was filed for Converting Hematology Based Data into an Inferential Interpretation under the direction of Prof. Ronald Raphael Coifman (NAS). No patent was filed for the statistical determination of myocardial infarct using two assays for creatine kinase MB. No patent was filed for the diagnosis of myaocardial infarct using a neural network under the supervision of Izaak Mayzlin, eminent mathematician from former Soviet Union; No patent was filed for the determination of myocardial infarct using Kullback Entropy.
My lab was the only one to get down to reliable measurements of transthyretin of 20 mg/L. I co-chaired the First International Transthyretin Congress in Strasbourg, at the invitation of Yves Ingenbleek, MD, PhD, Professor of Pharmacology, University Louis Pasteur, Strasbourg.
I chaired the 14th and was an invited participant in the 17th Ross Roundtable on Nutrition, Organized and Chaired the Beckman Roundtable on Pre-albumin in Los Angeles, was responsible for the AACC first document of Standards of Clinical Laboratory Practice with Lawrence Kaplan, and was recipient of the Labbe/Garry award of the Nutrition Division of AACC).
Other projects in normalizing the NT-proBNP for age and estimated glomerular filtration rate (eGFR), were successful, but widespread implementation is even more gradual than was TTR.
Could you tell us about the research project that had the most significance in your career?
You worked with two noted researchers – Gil David and Yale University’s Chairman of the Mathematics Department Ronald Coifman – to develop a software system which is today’s equivalent of electronic health records that gathers medical information, generates metrics and analyzes data in real-time, providing a health diagnosis for an individual’s medical condition.
4/19/2020
The Schwartz and Auslander Families
I was born a triplet to David and Lillian Bernstein on December 28, 1941, the first set of triplets born in Highland Park Hospital in some 20 years, but on graduation from Mumford High School, Detroit, Michigan in 1960, we were one of three sets of triplets. We were Larry, Leslie and Linda, who were preceded by Sharon, a sister two years older, also a December baby. Our parents were middle class and our father was a dental technician, so a family with four children was not easy to bring up. We always lived in a household of two families, with my uncle Irving and aunt Elsie Bernstein, living in the lower level, having two children, Barbara, who was our age, and Richard, who was the older brother. When we were born, under the circumstance of my grandmother, Bobby Mulvin (Mulvina in Hungarian), three calls were made in successive days to inform the family in Cleveland, Ohio, of our birth. My mother’s father and mother were Julius and Mulvina Schwartz, from the Hungarian edge of Austria on the Raba River, who moved the family to Cleveland as the intentions of Hitler became clear. My mother had two older brothers and a younger sister, David, Herman and Bernice. David had already been a United States citizen when the Schwartz family moved to the United States in 1931, and Herman was a third year medical student in Budapest after completing a year in Vienna, having been valedictorian of his high school class after special arrangement of his local catholic priest. But Herman had to move from Hungary months prior to graduation because immigration would close. Lillian was 18 years age when she brought her 11 year old sister to America. Julius and David worked in the dry cleaning business in Cleveland. There was also a Mulvina cousin, Biederman, who was a jeweler in Vienna who moved to Cleveland, but his father did not escape the Nazis. Their children were Alan and Marvin, Lois, Robert and Barbara (Liss), Lucille and Janice. Another two generations have passed. Robert was a merit scholar in upstate New York, became a reporter on the Miami Herald, and had three children. He died too young of leukemia. Barbara married and had 3 Wolfe children, two boys and a girl.
I have described the Cleveland side of the family. My mother worked making ties in Cleveland for a friend of my father’s family. She helped bring him to Detroit and married my mother. My father came from Czeckoslovakia, his father having a tree farm on the Carpathian mountains, near the border with Poland. He became a Schochet (kosher chicken). He had a sister, Rivka. Rivka married a cantor after her husband died. My grandmother was in the Auslander family. Auslander means out of the land. A rabbi brought his family out of Spain and changed the family name to Auslander. My grandfather was Meyer and grandmother was Rachel (Bobby Rochel). They lived two streets from the elementary school, so we had lunch at the grandparents house. My grandmother had sisters Esther, Edna, Katie, Jeanette. We go to a next generation rich in talent. This family lived in the city of Detroit, which has an interesting history.
The Jewish Community
Grandfather Meyer was very orthodox, but he shaved, and attended the Gelitzioner Shul, but our mother objected to her children going to an orthodox yeshiva school that was too rigid. Our mother read a lot to become knowledgable and also fluent in the English language. Our father read the Detroit Free Press and the business section daily. Some of our family went to the reform synagogue, Temple Israel, that did not use rigorous Hebrew in prayer. We attended the Bnai Moshe synagogue, which had Rabbi Moses Lehrman, whose daughter became an English teacher at our school. There was a cantor, and there was a superb reader of the Torah (Baal Koreh). The president of the Bnai Moshe was the founder of a salami that was the equal to that in New York.
Detroit
Detroit was a city on the Detroit River that was once known as Fort Ponchartrain at the time of the Revolutionary War with the British. There were Indians at the edge of the Upper Peninsula. The Upper Peninsula was obtained by Governor Lewis Cass from Wisconsin an a trade that made Toledo a part of Ohio. Detroit and the Detroit River became a crossing point for Negroes at the time of flight from the Southern states during the Civil War. Windsor, Ontario was a point of transfer of liquor from Winsor, Ontario. Detroit became important when Henry Ford brought automation into auto manufacturing, and it was followed by Dodge/Crysler and General Motors. Neighboring Dearborn, Michigan became a city where there was later a Ford Museum, and it was known to be only for whites and non-jews. There was also before my arrival an anti-Semitic priest, Father Coughlin. In addition, Henry Ford was known to disseminate “The Elders of Zion. So the city was somewhat divided, as perhaps other cities – like New York. Philadelphia, Chicago, and Los Angeles – that had distinctly jewish and black neighborhoods that one might consider ghettos. The city of Highland Park, within Detroit, was Polish. The jewish neighborhood migrated from Chicago Boulevard toward Livernois, and beyond to beyond Seven Mile Road, and eventually beyond Eight Mile Road, the Detroit border.
My early childhood was on Sturtevant, between Linwood and Dexter. Linwood extended to middle Detroit, where there was an automobile convention center. There was a theater at the corner of Linwood and Livernois. There was an upper middle class neighborhood adjacent to Oak Park, and a zoo on Woodward Avenue. The synagogue my family attended was on Dexter, and there was a butcher shop, a bakery, and the Dexter Davison Market. My aunt Edna had an ice cream parlor a short distance from the synagogue on Dexter. She had two sons and one became a doctor and the other a professor. The McCullough elementary school and across the street a United Hebrew School were walking distance from where my family lived, with many children on our street. Milk was delivered to a milkbox, and an alternative way of entering the home was through the milkbox. The next door neighbor had a dog named Blackie. He was child friendly. There were many children in the neighborhood. My best friend in elementary school was an Armenian boy, Michael Michalian.
High School and College
We moved from the old neighborhood at the time were to attend High School. My brother and I joined the chess club and learned from Peter Wolf, who excelled at it. Mumford High School chess club won the city championship over Redford High School, taking the cup four years in succession. I also found a friend in high school a grade ahead, Fred Baskin, who was extremely bright and very social. The triplets graduated from high school and entered WSU in 1960. When we finished high school we all went to Wayne State University (WSU), where I majored in chemistry, and was a premedical student. Fred had a Merit Scholarship. I prepared myself sufficiently so that if I were not to qualify for medical school, I could follow a suitable career. My older sister, Sharon, was a very fine pianist and she entered WSU with a General Motors Scholarship three years earlier. She excelled in mathematics. She has taught piano for years and still does so at 80 years age. Fred went on to graduate school in biochemistry at University of California, Berkeley and I went on to medical school at Wayne State University upon graduation. My sister Linda did graduate work and obtained a Master degree in biology at Wayne State, married a psychiatry graduate, and they moved to California and raised two boys. I shared the same room as Leslie, but I did not see changes in him that lead to attempted suicide and admittance to the hospital. The three of us spent a summer at the NIH in a study of Schizophrenia. Leslie went to San Diego to be near Linda.
I worked very hard in my first two years of medical school. I engaged in a graduate study in embryology under Harry Maisel in the Anatomy Department, studying the evolution of the proteins of the lens of the eye (crystallins) under Prof. Harry Maisel, but I also studied the changes in the isoenzymes of lactate dehydrogenase (LD). He was an inspiring scientist, but I also had the opportunity to learn electron microscopy under Maurice Bernstein in the same department. When I finished the Master degree I returned to finish the last two years of medical school. This was a valuable experience under two inspiring mentors. In the study of the evolution of the LD isoenzymes I became extremely interested in the work of Nathan Kaplan at the Graduate University of Biochemistry in Boston, and the work of one of his graduate students who looked at the changes in the wings of avians, depending on flight characterics. I chose to go to the University of Kansas Medical School for residency and PhD in pathology. When I arrived in 1968, the pathologist whose work interested me had left to carry on the chairmanship elsewhere, but I was fortunate to meet Masahiro Chiga, who had left an Acting Chairman of Biochemistry to return to pathology. He was an inspiration. I finished less than a year when he recommended that I go to the University of California, San Diego to work with Nathan Kaplan. He modestly said that he had worked with the muscle enzyme of adenylate kinase (myokinase) that is different than the liver enzyme, but he hadn’t had the insight that Kaplan had. I stayed in touch with him until his death. My mother developed gastric cancer, quite rare then, and I visited her several times before she died. I also dated an old Mumford schoolmate, Audrey Mellon, who I married before going to San Diego.
University of Calfornia, San Diego
I found myself in a completely different environment in San Diego. One part of it was the enormous scientific environment, not only with Kaplan’s laboratory his two competent two assistants, and his several postdoctoral students, but also my engagement with several staff biochemists. There were presentations in the hallway next to Prof. Kaplan’s office, and some were from outside research institutions. It was amazing how when the medical school was opened, it had drawn talents from all of the best institutions. An unintended benefit was the beautiful ocean, the nearby La Jolla, and nearby other research centers. Dr. Kaplan was the Editor, and he cofounded Methods in Enzymology with Sidney Colowick, who had worked with Carl and Gerty Cori (Nobel Laureates) in St. Louis. They had both worked with Fritz Lippman in the discovery of Coenzyme A , the cofactor that acts as an acyl carrier, and either activates the acyl group for group transfer or electrophilic attack, or increases the acidity of the protons adjacent to the carbonyl group. He shared the Nobel Prize in Physiology in 1945 with Hans Krebs, who elucidated the Krebs cycle. Kaplan’s role in the discovery was significant. Interestingly, Hans Krebs work was related to work carried out in the laboratory of Otto Warburg (Nobel Laureate, 1937)), whose work pioneered the study of mitochondrial impairment if cancer.
My own work was not with lactate dehydrogenase, but with Malate dehydrogenase, a critical enzyme linked to mitochondrial function. While LDH catalyze the conversion of pyruvate to lactate with NADH as cofactor and the transfer of a proton, the reverse reaction was inhibited by a ternary complex formed by LDH-NAD- and lactate, but this reaction was weak with the muscle type LDH compared to the heart type LDH. In a similar manner the malate dehydrogenase had a mitochondrial and cytoplasmic isoenzyme, the mitochondrial MDH forming a ternary complex, but not the cytoplasmic enzyme. I spent many months purifying the mitochondrial enzyme from 50 lb of chicken hearts with first an ammonium sulfate precipitation, then a column separation, and dialysis. A study of the mitochondrial malate dehydrogenase was followed by stopped flow analysis and that showed the inhibition by transfer of the hydrogen to form a ternary complex.
I returned to residency in pathology at UCSD under an NIH fellowship with Averill Liebow in the next year. Liebow was an internationally known expert in pulmonary pathology. He was also very amazing. A resident from Yale referred to Liebow noticing him sleeping in the back row and the professor called his name, the son of so and so, you can’t sleep in my class. His car was the first in the lot, until I came. Then when I went to the VA Hospital and parked on the other side, he noted that I parked around the corner. The chief of chemistry at the VA was an outstanding teacher and biochemist who subsequently took a position at Beckman-Coulter. I set up an assay in a study of swimming rats with Liebow. My first daughter was born during my residency and it was fascinating watching her learn to stand up. I took her to the San Diego zoo on weekends and she would stand up in her crib and say zoo, zoo. It was at this time that I collected urine specimens for a study of adenylate kinase with Percy Russell, and also took serum specimens from a study of creatine kinase MB in myocardial infarction that was done by the cardiologist Burton Sobel for my own study that was published.
At the end of my residency I had to give two years for my time deferred from the Vietnam War. Liebow called the Armed Forces Institute of Pathology in Washington to give me the best placement. I then spent the next two years working in orthopedic pathology with Lent C. Johnson, who was quite a genius. He determined the normal ratio of bone forming to bone removing cells, and did pioneering work in bone cancer. Liebow wanted me to return after the two years, but he had a stroke. At the end of two years I took a pathology position at the University of South Florida, Tampa, under Herschel Sidransky.
Herschel was an outstanding researcher from University of Pittsburg Medical School. He had several outstanding researchers in his department. I returned to my studies of malate dehydrogenase and in particular, the mitochondrial malate dehydrogenase in hepatic cancer from Herschel Sidransky’s animals. I had a grant from the Cancer Society. I also had the support in statistics from a mathematician.
Herschel became the Chairman of Pathology at George Washington University, Washington, DC. Several faculty went with him, but I received a substantial salary increase and a supportive offer from the University of South Alabama, Mobile, with a very enthusiastic pathology chairman. Just prior to leaving Florida, Naomi was born. I took on a role with the Medical Technology Program, and I also participated in program reviews, and some time later was on the National Committee for Clinical Laboratory Standards. The Chairman was a capable and enthusiastic neuropathologist who intended to build a good department, but it was not long after that the Chair of Medicine, also the Dean, set up a clinical laboratory for his own interest, without merit. I submitted a cancer grant proposal that was approvingly reviewed by the Chairman of Physiology. It was approved by the NIH without funding, with suggestions to consider. That was a point that I chose to move, and after two years, I moved the family to Des Moines, Iowa to work at the Iowa Methodist Medical Center, the second largest after University Hospital. The President of the hospital sent me a high school student and we completed a project on fetal lung maturity that we published. However, the move was not a good match, as the Chairman’s main concern was outside laboratory work and there was also a laboratory manager who was manipulative.
After two years we moved to Binghamton, New York to a position with Gustavo Reynoso, who came from Rochester, New York and was a very respected pathologist. There was a consolidation of hospitals that led to Dr. Reynoso taking the chairmanship of pathology at Norwalk Hospital, in Norwalk, Connecticut, and he procured a position for me at Bridgeport Hospital, in Bridgeport, CT. The move was very good with an excellent staff in pathology, and I was the director of chemistry and blood bank. This time I stayed for 20 years, and developed a very good relationship with the medical staff, the Chairman of Pathology, Dr. Marguerite Pinto, and particularly with my supervisors in Blood Bank and Chemistry. My Blood Bank supervisor married and moved to Greece and eventually was in charge of the Athens Blood Program.
My relationship with the residents in medicine and cardiology was very collaborative. When I was in the hospital recovering from a femoral fracture, I received a call from I.J. Good, Chairman and Editor of a mathematics journal to whom I had sent cardiac enzyme data some years before. He had finished and validated a program “Diagnosis of acute myocardial infarction from two measurements of creatine kinase isoenzyme MB with use of nonparametric probability estimation”, and they successfully ran the data. We published the paper in Clinical Chemistry. The President of the College of American Pathologist complimented the work at a national meeting. I also met another pathologist, Rosser Rudolph, at a pathology meeting and he had developed a powerful mathematical program that determined the entropy of diagnostic data. We collaborated for many years. In addition, I was really privileged to work with the father of my daughter’s classmate, Isaac Mayzlin, who was an important mathematician at Moscow University. We developed an neural network algorithm for myocardial infarction.
I had a very long, satisfying role in collaboration with Dr. Walter Pleban, who was the surgeon in charge of the only burn unit in Connecticut. I had been engaged in the nutritional support program with Dr. Pleban for some years because of my work on transthyretin. Unfortunately, the criteria using decrease in serum albumin that was in use was very inadequate for early recognition. Transthyretin is a plasma protein that binds to vitamin A and declines very early in protein malnutrition. A decline in transthyretin results in impairment of methionine metabolism. I also had a longstanding relationship with Prof. Yves Ingenbleek at University Louis Pasteur, Strasbourg, in this work. When Stanley Dudrick became the Chairman of Surgery, it was a fortunate circumstance. Stanley was the pioneer in developing intravenous nutrition and was nominated for the Nobel Prize for his work.
A year after Yale University took charge of the Bridgeport Pathology Department, I took a position as Chief of Clinical Chemistry and Blood Bank at the Methodist Hospital of Brooklyn. I had a very good relationship with surgery and medicine, and had superb projects with the residents, but also had excellent high school and college students work on projects. I was 65 years old five years later, and returned to work at Norwalk Hospital in charge of the Blood Bank while the position was recruited. After finishing my work there, I went to Yale University and developed a project with Ronald R. Coifman, the retired Chairman of Mathematics and his graduate student. It lead to the development of a powerful algorithm for interpreting the hemogram that we published. There is a substantial body of research being published of a similar nature, but it is not at all clear whether or how this will be incorporated into the electronic medical record. It reminds me of the support I had at Bridgeport Hospital using a laboratory system designed by Dr. Perry Seamonds that eliminated nonessential examination of peripheral smears by rules criteria. This laboratory system also alleviated the volume of laboratory testing to relieve the burden on the physicians. A different problem I later noticed was that the Hospital Systems that were later introduced had the laboratory, but did not include the Blood Bank! However, as the electronic medical record has evolved it has taken an enormous physician, nursing, and provider time that does not justify a reduction in staff.
After I had been done with my Yale project, I developed a visual problem and stopped driving. I had problems I would later realize. I had had two incidents in a few years that I drove my car off the road because of sleep apnea. I was walking in my neighborhood and had to stop and hold on to a tree for balance. In the case of sleep apnea, it was diagnosed earlier in a sleep apnea study in Brooklyn. I had a study at Yale that brought to my realization that I had thyroid cancer, for which I had thyroidectomy. However, I had diplopia after surgery which disappeared some time later. We moved to Northampton, Massachusetts when our daughter, Naomi and her husband Daniel with grandson Joseph moved, Naomi taking a teaching position at Holyoke Community College, and Daniel working as a neurologist at the VA hospital.
Prior to moving I was contacted by Aviva Lev-Ari, PhD, RN who was building an online medical forum known as Leaders in Pharmaceutical Business Intelligence (LPBI) Group,and I became the Chief Scientific Officer (CSO). Over the decade I wrote many articles (1,390) in the Open Access Online Scientific Journal http://pharmaceuticalintelligence.comthat were included in 16 organized e-Books in Medicine. Dr. Lev-Ari’s accomplishment is quite impressive. The e-Books are all available on Amazon.com
I stopped contributing two years ago, but a graduate student had read my work and wanted my academic guidance (in Canada). She finished her thesis and graduated a year ago. It was a privilege to work with her. Since moving to Northampton, we has been in a very good community at Lathrup.
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