Outline

Click here for the Table of Contents with a link to each chapter.

1.    Introduction and Medical School start

A.    Professional Education and Medical Training

B.    Background

C.   Getting to Medical School

D.   Research Fellowship and Master of Science Program after two years of Medical School

2.    Initial Research Experience (Wayne) – Blood Coagulation Mechanisms 1947-1949 and transfer to Harvard Medical School 1949-1951

A.    Department of Physiology

1.     Structure

2.     Master of Science Program

3.     A new Murphy’s Law

B.    Background to Coagulation Research

1.     Four known Clotting Factors

2.     Research Sites: Iowa (1930s – Biology), Wayne (1940s – Protein Fractionation)

3.     New Coagulation Factor (Factor 5, Accelerator Globulin)

C.   J.L. Fahey Contributions

1.     Accelerator Globulin (AcG)/Factor 5 Stability

2.     Tiselius Electrophoresis

3.     Clinical Studies – John Olwin

4.     Scientific Publications, Conferences, Societies

D.   Visits to International Research Centers/Europe – Summer 1949

E.    Harvard Medical School

1.     Transfer to Harvard Medical School, September 1949

2.     E.J. Cohn (and John Edsall) – Blood Characterization and Preservation Laboratory, Harvard Medical School, Summer 1950

3.     Summary 1947-1951

3.    Medical Residency in New York and Wegener’s Granulomatosis

A.    Medical Residency – Columbia-Presbyterian Medical Center 1951-1953

B.    Wegener’s Granulomatosis (published 1954, Amer. J. Med.)

4.    National Cancer Institute (NCI), National Institutes of Health (NIH) 1953-1954

A.    Background

1.     Public Health Service (PHS)

2.     National Institutes of Health (NIH)

3.     National Cancer Institute (NCI)

B.    Clinical Center as an NIH Research Resource

1.     Concept

2.     Opening – July 1953

3.     How I got to the NIH

C.   NIH Features and Resources/Scientific environment

D.   Established a Clinical Research Laboratory focused on Plasma Proteins

E.    Life outside the NIH

5.    Research Projects at NCI/NIH 1955-1959

A.    Waldenstrom Macroglobulinemia – Introduction of New Therapy

– Clinical Description and Malignant Morphology
– Hyperviscosity Syndrome
– Plasmapheresis Therapy
– Dutcher Bodies
– Intranuclear glycoprotein (IgM)

B.    Development of Therapy with intravenous arginine for clinical ammonia toxicity

C.   Evaluation of newly developed anion (and cation) exchange chromatography methods for isolation and characterization of plasma proteins

D.   Characterization of plasma protein changes in disease

1.     Malignant diseases

2.     Antibodies in Autoimmune diseases

E.    Murine Plasma Cell Tumors and Myeloma Proteins – a new animal model for multiple myeloma in humans

6.    National Institute of Medical Research (Mill Hill), London 1959-1960

A.    Purposes

B.    Resources and Environment

C.   Research Projects – Immunologic Methodologies / Functions

·      Biosynthesis and Structure of Immunoglobulins – B. Askonas

·      Initiated Research on the Impact of Plasma Cell Tumors on normal immune functions – J. Humphrey

·      Gm Genetic marker only on Human IgG gobulins, not Ig or IgM macroglobulins

D.   Later British Associations

E.    Trivia

7.    Immunoglobulin Discoveries, NCI 1960-1971

A.    Key Concepts

B.    Immunology Branch established in NCI/NIH – Increased Resources

C.   Characterization of the Major classes of Human Immunoglobulins (IgG, IgA, IgM)

D.   Discovery of IgD – by a different approach

E.    Identification of Human Immunoglobulin Subclasses (IgG1, IgG2, IgG3 – later IgG4)

F.    Major Classes and Subclasses of Murine (mouse) Immunoglobulins – Identification and characterization of IgG2 (G2a, G2b), IgG1, IgA, IgM

G.   Quantitative Methods for Immunoglobulin Classes

H.   Metabolic Characterization and Factors Controlling plasma levels of the Immunoglobulin Classes – IgG is different

I.      Immunoglobulin synthesis within the Plasma Cell Replication cycle

J.     Immunoglobulin Changes in Disease

K.    WHO Immunoglobulin Nomenclature and state-of-the-art Research Conferences and International Immunology (Immunoglobulin) Reference Standards in 1960s

L.    Cancer and Transplantation Immunology: Cytotoxic Antibodies and Membrane Antigens

M.   Initiation of Courses on Immunology at NIH

8.    UCLA Department of Microbiology and Immunology 1971-1981

I was recruited as Professor and Chairman in Department of Microbiology and Immunology with a Joint appointment in Department of Medicine, UCLA School of Medicine

A.    1971 – Status of the Department

B.    1971-1975 – Faculty and Programs

1.     Microbiology

2.     Immunology

C.   1976-1980 – Faculty and Programs

1.     Microbiology

2.     Immunology

3.     Oncology

D.   1981 – Status of the Department

E.    My first NIH grants

9.    New Interdepartmental Programs in Immunology and in Cancer at UCLA 1972 – 1990

A.    UCLA Cancer Center – Creation and Initiation

Participant in three successful Cancer Center Grant Applications to NCI/NIH for Planning, for Construction (Factor Building) and for Comprehensive Center designations and funding.

B.    Existing Immunology Faculty and Projects at UCLA in 1971

C.   Clinical Immunology Research Laboratory (CIRL) established for study of Human Immune System cells and functions

1.     Identify lymphocyte subgroups with distinct phenotypic and functional
features – J.L. Fahey

2.     Functional Tests including Antibody-dependent Cellular Cytotoxicity (ADCC) – F. Hoffman,

J. Zighelboim

3.     Identification and Quantification of Cytokines that influence immune functions – P. Nishanian

4.     Measurement and significance of soluble products of immune activation (Beta2m, neopterin, IL-2R, etc) as biomarkers and as evidence of specific cytokine function

5.     Quality Control of new Immunologic Assays

6.     Specific Research Areas

7.     Cooperation with UCLA Pathology and Hospital Laboratories to provide Immunologic assays to meet Hospital needs

D.   Tumor Immunology

1.     Lymphoma – J. Zighelboim

2.     Bladder Cancer – C. O’Toole

3.     Pediatric Malignancies – R. Seeger

E.    Immune-based Therapies

1.     Stimulation (Cancer) – J. Zighelboim, B. Bonavida

2.     Suppression (autoimmune diseases) – G. Ellison (Neuro), Oto Martinez-Maza

3.     Restoration of Function in Pediatric Immune Deficiencies – R. Stiehm

F.    Clinical Bone Marrow Stem Cell Transplantation – Restoration of Immune System (after Ablation) by Stem Cells. Autologus and Heterologus Transplants – Homeostatic mechanism controlling CD4, CD8 and total Lymphocyte numbers – R. Gale, M. Territo, R. Mitsuyasu

G.   Immunology Education and Research Training Program

1.     Undergraduate and Professional Education

2.     Two Immunology Research Training Grants: NCI in 1975 and NIAID in 1977

3.     Weekly Seminars – Current research topics

4.     International Guests and Coworkers

5.     Medical Laboratory Immunology Training for PhDs & MDs

H.   Start of Clinical Immunology and Allergy Division in Dept of Medicine

10.   Center for Interdisciplinary Research in Immunology and Disease from 1978

A.    Human Immunobiology Group Concept at UCLA

1.     Clinical Immunology Core Faculty

2.     Immunology as a multi-departmental activity and distinct entity at UCLA

3.     Role in UCLA School of Medicine

B.    Center for Interdisciplinary Research in Immunologic Diseases (CIRID)

1.    NIAID Announcement of plans for four Centers – 1977

2.    UCLA CIRID Applications and Awards – 1978 and 1983

3.    CIRID Operations and Evolution

4.    Washington politics: Getting the CIRD program funded – a note from NIAID Director, Dr. Richard Krause – 30 years later

11.   AIDS from 1981

A.    The First Year

1.    Why AIDS was discovered at UCLA

2.    Characteristic Immunologic features of AIDS identified in original publications and follow up

3.    NIAID Notification and Contacts with National Colleagues

4.    Funding for UCLA research on AIDS

5.    Pre-Aids Proposition – CD4 T cell measurements could identify individuals with reduced immune cells and early (asymptomatic) stages of disease

6.    Initial Epidemiology study started at UCLA – R. Detels

7.    At-risk populations contacted

8.    Caring for AIDS patients

9.    Addressing Public Health, Safety, Social and Educational Issues

B.    Core AIDS Research Resources in CIRID

1.     Clinical Immunology Research Laboratory (CIRL) facilities

2.     Flow Cytometry of T helper (CD4) and T Cyototoxic (CD8) and other Lymphocytes – Ingrid Schmid, Michael Weaver and Janis Giorgi

3.     Diagnostic HIV Antibody and Western Blot Tests – Pari Nishanian

4.     Development of Modified p24 antigen quantitative technique needed for HIV diagnosis in infants – Pari Nishanian

5.     Creation of Quality Control Procedures (CIRID) and External Proficiency Testing Programs to meet National Research Needs – Najib Aziz

6.     The QASI International program – Quality Assessment and Standardization for Immunological measures relevant to HIV/AIDS – Frank Mandy

7.     Adventures and Mishaps in Real Life

C.   Immunopathogenesis Research including Immune Activation in HIV/AIDS

1.     Immune Deficiency

2.     Immune Activation and Cytokine Increases

3.     Increased Neopterin and Soluble Plasma Markers of Cytokine Activity

4.     Simian Immune deficiency Virus Infection – Immunologic changes

D.   Epidemiology Research

1.    Multi-Center AIDS Cohort Studies (MACS)

2.    Immune Activation – Indicator of Prognosis separate from CD4 T cell levels

3.    Disease Course – Constant Progression vs. Plateaus and Inflection Points

4.    Virology

E.    Therapy Studies

1.   Initial Studies (1982-1988)

a.    Bone marrow transplantation

b.    Aspirin, High fat

2.   Interleuken-2 (IL-2) administration

3.    Association with AIDS Clinical Trials Group (ACTG)

a.    Zidovidine (AZT)

b.    Thalidomide

c.     Interferon gamma

F.    AIDS Education and Community Outreach Programs – the Early Years 1981-1992

1.    Overall

·      Assembled Authoritative Information about AIDS for Health Care Professionals including Physicians (interested and not-so interested), Nurses, Dental workers, Laboratory Technicians; also Health Agencies, Fire and Police departments, community organizations, Latinos. Questions and needs in the various groups were determined.

·      Organized Conferences, Lectures and printed/published Guidelines for diagnosing and treating AIDS and for care of AIDS patients. Special attention was given to procedures needed to protect those in contact with AIDS patients (household and medical persons) from becoming infected with the AIDS virus.

2.    CIRID/UCLA Response – First Phase (1982 – 1986) – Cindi Dale

·      Physician Conferences for Health Personnel in LA County – 1984, 1985

3.    AIDS Reference Guides for Medical Professionals (1984, 1986, 1988, 1996)

4.    CIRID/UCLA Response – Second Phase (1987-1992) – Diana Shin

·      Nursing Education Programs: LA and National – with Jacquelyn Flaskerud

·      AIDS Training Modules for Physicians – Charles Lewis

·      National AIDS Research Conferences

·      Third Edition of the AIDS/HIV Reference Guide for Medical Professionals

·      Fourth Edition of the HIV/AIDS Reference Guide for Medical Professionals

·      Minority Aids Educational needs

·      A National Strategy Symposium on Latinos and AIDS – O. Martinez-Maza

·      UCLA Dental School – A. Wong

G.   Independent UCLA Programs with some CIRID Associations

1.    Cellular Immunology and Advanced Flow Cytometry – Janis Giorgi

2.    IL-6 – Otoniel (Oto) Martinez-Maza

3.    Kaposi Sarcoma and other Neoplasms – Ronald Mitsuyasu and Jerome Groopman

4.    CARE Center, Immune-Based and Gene Therapies – Ronald Mitsuyasu and Judith Currier

5.    Pediatrics – Yvonne Bryson and Karin Nielsen

6.    Behavioral Studies in AIDS – Margaret Kemeny and Steve Cole

7.    Social and AIDS Prevention Programs – Mary Jane Rotheram

8.    Nursing and Patient Care Research and Resources – Jacquelyn Flaskerud (AIDS/HIV Infection: A Reference Guide for Nursing Professionals)

9.    AIDS Education Programs in India for Nursing Schools and for Traditional Medicine doctors and meeting the needs of women and children – Adey Nyamathi

10. Participitory Prevention of AIDS: Arts in Action – David Gere

11. UCLA AIDS Institute – Irvin Chen, Jerome Zack

H.   A Changing Situation – post 1992

12.   Idiopathic CD4 T cell lymphocytopenia – A New Disease from 1993

A.  Unexpected CD4 T cell deficiency – 1993

B.  A Major Change (1996) and New Therapies

C.  In Retrospect – after 17 years

13.   Psychoneuroimmunology at UCLA 1978-2006

A.    Introduction

1.    General

2.    Hypnotic Suppression of delayed-type Hypersensitivity Reactions and Asthma – 1963

3.    Norman Cousins at UCLA

4.    Overview – Three Systems involved in PNI

5.    Hypothalamic-Pituitary-Adrenal Cortex (HPA) Axis

6.    Issues of Biological Access and Experimental Design

B.    Specific Studies

1.    Fawzy Fawzy – Positive attitudes/malignant melanoma

2.    George Solomon and Bruce Naliboff – Shaking up immunity

3.    Margaret Kemeny – Psychological Factors Impacting on HIV/AIDS

4.    Anne Futterman – Positive/Negative emotions – Method actors

5.    Francesco Chiappelli – Effect of Endorphin on Immune System

6.    Julie Bower – Stress relating to breast cancer

7.    Steven Cole – Social Regulation of Gene Expression in the Immune System

C.   PNI Center at UCLA – Michael Irwin

1.     Education & Training

2.     Sleep and other studies

D.   Complementary Medicine

1.    Traditional Medicine

2.    Tai Chi and Yoga

a.     Some positions – not suitable for many people

b.     Breath Yoga

3.    Placebo effects

E.    Commentary

1.    Data Analysis – Confirm and explain extremes, comparison of degrees of response

2.    Request for clarity on frequency and duration of response to intervention and description of those who are helped and those not helped

3.    Graduate Student Projects

14.   Clinical Immunology Society: The Early Years 1984 – 1989: I. Introduction, II. Preparation and Achievements

Part I – Introduction

1.    Background

2.    Clinical Immunology as a Distinct Medical Science

3.    A Precedent Existed in the Development of Clinical Oncology as a Clinical Specialty

4.    New Immune-Based Therapies

5.    AIDS

6.    Medical (Clinical) Laboratory Immunology

7.    Advocacy for Clinical Immunology – A Social and Professional Responsibility

Part II with S. Kanowith-Klein – Preparations and Achievements

A.    1984 – 1985

1.    Academic Immunology – Research Advances Focused on Immune System: Components, Functions, and Regulation

2.    Clinical Disease Specialties and Subspecialties – Involvement of Immunology and Immunologists

3.    Immunological Laboratory Resources Needed for Clinical Research and Care

4.    Procedures and Therapies Requiring Special Expertise Unique to Clinical Immunologists

5.    American Association of Immunology (AAI) and Other Organizations, National Institutes of Health (NIH), Especially National Institute of Allergy and Infectious Diseases (NIAID)

6.    Meetings to Plan a Society and Annual Conference

7.    Decision to Proceed

B.    1986 – Provisional Organization of the Clinical Immunology Society (CIS) and the Initial Annual Conference on Clinical Immunology (ACCI)

1.    Working Group to develop CIS

2.    CIS Goals

3.    Initial Conference on Clinical Immunology – Preparation and Conduct

4.    Subsequent Annual Conferences on Clinical Immunology

C.   1987 – 1989 – The New Clinical Immunology Society: CIS Organization

1.    Professional Structure

2.    Administration and Operational Issues

3.    Finances and Fundraising

4.    Use of management companies for the CIS and ACCI

5.    Membership

a.    Overall

b.    Ph.D. Scientists in CIS

c.     Women in CIS

d.    Scientists in Industry

6.    Journals and Educational Activities

D.   Relationships with Existing Organizations, Conferences, and Certifications

1.    Immunology – AAI

2.    Clinical Medicine – Subspecialties and Board Certification

a.    Allergy

b.    Organ-Based Medical and Pediatric Subspecialties

c.     Requirements for a New Specialty Field in Medicine

3.    Medical (Clinical) Laboratory Immunology

4.    International – International Union of Immunological Societies (IUIS)

E.    Summary and Opportunities

F.    Tables

1.    Participants in forming the Clinical Immunology Society, 1986

2.    Procedures and Therapies Requiring Special Expertise unique to Clinical Immunologist (R. O’Reilly, MD), 1986

3.    Program. First Annual Conference of Clinical Immunology, 1986

4.    Topics for Poster and Workshop Presentations, 1987

5.    CIS Publications: Brochures, Newsletters and Information

G.   Addendum 2011

1.    International Recognition of the Importance of Clinical Immunology (1970, 1971 Conferences – WHO publication 1972 – preceding CIS by 15 years. Key roles of John L. Fahey and Noel Rose

2.    Federation Of Clinical Immunology Societies (FOCIS, 2001)

3.    CIS Presidential Awards to John L. Fahey and Noel Rose, 2011, (on the 25th Anniversary of the Clinical Immunology Society) for contributions to the science and practice of clinical immunology

15.   International Immunology and AIDS: Education, Research, Capacity Building and Cooperation 1963-2010

A.    Introduction

B.    World Health Organization (WHO) 1963-1976

1.    Howard Goodman

2.    International Cooperation

3.    Immunology Education and Training in Developing Countries

4.    AIDS

C.   International Union of Immunological Societies (IUIS)

1.    International Union of Immunological Societies (IUIS) (1971-2002) and development of International Immunology Congresses

2.   Clinical Immunology Committee

3.   Regional Immunological Societies of Latin America, Africa, Asia, Soviet Union (1990-2002)

4.    Notable Support – NIH award with more than the originally requested funding for an AIDS meeting in Africa

D.   NIH/Fogarty International Center Programs

1.    NIH Office of AIDS Research – Coordinated with NIAID, NCI, NIMH and other NIH Institutes

2.    Fogarty International Center

3.    Development of the AIDS International Training and Research Program (AITRP) at UCLA – in Epidemiology and Public Health (R. Detels)

E.    AITRP for Postdoctoral Clinical Science – Training Program, Latin America (Brazil, Chile, Mexico) and Asia (China and India) – J.L. Fahey

1.    Initial Postdoctoral Program (1990-1995)

2.    Revised AITRP Postdoctoral Clinical Sciences Program (1996-2010)

a.    Considerations

b.    Revised Content

3.    Development of Pediatric AIDS Leadership at UCLA: Work in Brazil and Mozambique, Leadership in NIH-Funded International Pediatric AIDS Programs – Y. Bryson and K. Nielsen

4.    China

F.    Other International Programs

1.    Japan

2.    External Proficiency Testing – QASI Program– Quality Assessment and Standardization for Immunologic measures relevant to HIV/AIDS

G.   Commentary

16 Issues

16.   Summary: UCLA-India Biomedical Science Activities 1994-2010 – Looking Ahead

A.    Engagement with India at two times of Medical Research Change

B.    UCLA-India Biomedical Sciences Training Program (1994-2010)

C.   Summary of UCLA-India Biomedical Science Achievements (Table 1)

D.   India Fellows and Institutions (Table 2) – a partial list

E.    UCLA Faculty working with India (Table 3)

F.    Essential Preparations for the Future: UCLA Associations with major Medical Research and Education Institutions in India

G.   Diagram of the Major Biomedical Research Components of the Government of India (Figure 1)

H.   Looking Ahead – Another time of Medical Research and Education change

I.      Map of India – locations of Indian Institutions in UCLA-India Program

(Figure 2)

17.   India – Biomedical Science Education and Research Capacity Building 1968-2010

Prologue

A.    WHO Immunology Courses in India – 1968, 1970

1.    1968 – Second course plus review of trainee activities in many parts of India

B.    UCLA-India Biomedical Sciences Program (1994-2010)

1.    Introduction

2.    Linkages established with Indian Institutions

3.    The UCLA-India Postdoctoral Training Program at UCLA and in India

a.    Trainee selection

b.    Educational structure

C.   All India Institute of Medical Sciences (AIIMS) – 1994-2010

1.    Introduction – New Delhi, funded by Ministry of Health

2.    Microbiology

3.    Medicine I

4.    Medicine II

5.    Pediatrics

6.    Psychiatry

7.    College of Nursing at AIIMS

8.    Educational Programs

a.    UCLA-sponsored Scientific Workshops in India

b.    Training Program

c.     Continuing educational courses

9.    Issues at AIIMS

10. Key Consultant

D.   Indian Council of Medical Research (ICMR)

1.    Introduction – like NIH, funded by Ministry of Health

2.    Director General Professor N.K. Ganguly & Central Offices, New Delhi

3.    Tuberculosis Research Center (TRC), Chennai

4.    National Institute of Epidemiology (NIE), Chennai

5.    National AIDS Research Institute (NARI), Pune

6.    National Institute for Cholera and Enteric Diseases (NICED), Kolkata

E.    Armed Forces Medical Services (AFMS), New Delhi and Armed Forces Medical College (AFMC) in Pune

1.    How I got here

2.    Initiating AITRP linkage with the AFMS

3.    Why was the Military important?

4.    What was accomplished?

5.    Introduction of HAART Therapy in India

6.    Trainees have had diverse careers

F.    Other Major Medical Institutes in India – with UCLA associations / contacts

1.    Malauna Azad Medical College, New Delhi

2.    Other Medical Schools

3.    Tata Institute of Social Sciences – Mumbai

4.    Other UCLA Projects

G.   Department of Biotechnology (DBT) – Ministry of Science and Technology – New Delhi

1.    Basic Research Institutes

2.    DBT projects funded at Medical Schools

3.    DBT developing new programs: (a) UNESCO Centre for Biotechnology, (b) the Translational Health Science and Technology Institute

H.   Traditional Systems of Medicine in India (AYUSH), New Delhi. Funded by the Ministry of Health.

1.    How I got involved . . . and why

2.    Overview: Indian Systems of Traditional Medicine, AYUSH, Central Councils for Research – in Ayurveda, Homeopathy and more

3.    Introduction to Clinical Research

4.    HIV/AIDS Education for Traditional Medicine Practitioners

5.    Additional Issues

I.      Public Health Education, Health Policy and Program Assessment

J.     Other Institutional Players in India with impact on Health Research, Education and Capacity Building

1.    National AIDS Control Organization (NACO)

2.    U.S. Embassy – Health Attaches, Manmohan Saxena

3.    Other U.S. Academic Institutions

4.    Foundations – Gates, Clinton

5.    NIH, Fogarty International Center, Office of AIDS Research, NIAID and Clinical Center

18.   Colleagues, Postdoctoral Fellows, Laboratory Associates, Administrators and Visitors 1953-2010

A.    National Cancer Institute, National Institutes of Health and British Colleagues 1953-1971

B.    University of California in Los Angeles, (UCLA): Schools of Medicine, Public Health, and Nursing plus International Colleagues 1971-2010